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Title:
COMPOSITIONS AND METHODS FOR BIOSYNTHETIC PREPARATION OF UROLITHIN COMPOUNDS AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2019/212997
Kind Code:
A1
Abstract:
The present disclosure relates to compositions and methods for the biosynthetic preparation of urolithin compounds, pharmaceutical compositions and kits containing them, and methods of using them.

Inventors:
KIM SINIL (US)
DOROFEYEVA NATALIYA (US)
SCHWIER ALEXANDRIA (US)
ARONSON GARY D (US)
Application Number:
US2019/029748
Publication Date:
November 07, 2019
Filing Date:
April 29, 2019
Export Citation:
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Assignee:
REJUVENATION THERAPEUTICS (US)
International Classes:
C12N1/20; A23L33/105; A23L33/135; A61K31/366; A61K35/741; C07D311/80
Domestic Patent References:
WO2014147280A12014-09-25
Foreign References:
EP2481298A22012-08-01
US9573922B22017-02-21
UA23109U2007-05-10
Other References:
MARÍA V. SELMA ET AL: "Isolation of Human Intestinal Bacteria Capable of Producing the Bioactive Metabolite Isourolithin A from Ellagic Acid", FRONTIERS IN MICROBIOLOGY, vol. 8, 7 August 2017 (2017-08-07), XP055599567, DOI: 10.3389/fmicb.2017.01521
FRANCISCO A. TOMÁS-BARBERÁN ET AL: "Urolithins, the rescue of "old" metabolites to understand a "new" concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status", MOLECULAR NUTRITION & FOOD RESEARCH, vol. 61, no. 1, 20 June 2016 (2016-06-20), DE, pages 1500901, XP055537524, ISSN: 1613-4125, DOI: 10.1002/mnfr.201500901
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Attorney, Agent or Firm:
AN, Na (Morrison & Foerster LLP, 755 Page Mill RoadPalo Alto, California, 94304-1018, US)
Download PDF:
Claims:
CLAIMS

What is claimed is:

1. A composition comprising:

(a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a second component comprising one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces.

2. The composition of claim 1, wherein the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus (e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus ), Lactobacillus paracasei (e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum (e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02),

Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis (e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum (e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum (e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus .

3. The composition of claim 1, wherein the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

4. The composition of claim 1, wherein the ratio of the first component to the second component is about 1:1 to 25:1 (w/w).

5. The composition of any one of claims 1-4, wherein the probiotic species is at least 1 CFU (e.g., 1, 101, 102, 103, 104, 105, 106, 107, 108, 109, 1010, 1011, or 1012 CFU) per gram at the time of manufacture.

6. The composition of any one of claims 1-5, further comprising a lipid.

7. The composition of any one of claims 1-4, wherein the lipid is selected from a group consisting of fish oil or a salt thereof, algal oil, chia seed oil, eicosapentaenoic acid or a salt or ester thereof, docosahexaenoic acid or a salt or ester thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, or a mixture thereof.

8. The composition of any one of claims 1-7, further comprising milk.

9. The composition of claim 8, wherein the milk is selected from the group consisting of soy milk, human milk, cow milk, goat milk, oat milk, almond milk, rice milk, hemp milk, cashew milk, and coconut milk.

10. The composition of any one of claims 1-9, further comprising formula (e.g., baby or toddler formula).

11. The composition of claim 10, wherein the formula is selected from the group consisting of milk formula, dairy-free formula, soy-free formula, lactose-free formula, and vegan formula.

12. The composition of any one of claims 1-11, further comprising a sugar.

13. The composition of claim 12, wherein the sugar is selected from the group consisting of glucose, fructose, N-acetylglucosamine, galactose, sucrose, mannose, maltose, and lactose.

14. The composition of any one of claims 1-13, further comprising a bacteriophage selected from the group consisting of LH01 - Myoviridae, T4D - Myoviridae, LL12 - Myoviridae, LL5 - Siphorviridae , and PBC1.

15. The composition of any one of claims 1-14, further comprising urolithin A, urolithin B, or a mixture thereof.

16. The composition of any one of claims 1-15, further comprising a pharmaceutically acceptable carrier, excipient, binder or diluent.

17. The composition of any of claims 1-16, wherein the composition is in the form of a food product or dietary supplement.

18. A kit comprising:

(a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a second component comprising one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces.

19. The kit of claim 18, wherein the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus (e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus ), Lactobacillus paracasei (e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum (e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02),

Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis (e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum (e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum (e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus .

20. The kit of claim 18, wherein the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

21. The kit of any one of claims 18-20, wherein the ratio of the first component to the second component is about 1:1 to 25:1 (w/w).

22. The kit of any one of claims 18-21, wherein the probiotic species is at least 1 CFU (e.g., 1, 101, 102, 103, 104, 105, 106, 107, 108, 109, 1010, 1011, or 1012 CFU) per gram.

23. The kit of any one of claims 18-22, further comprising a lipid.

24. The kit of claim 23, wherein the lipid is selected from a group consisting of fish oil or a salt thereof, algal oil, chia seed oil, eicosapentaenoic acid or a salt or ester thereof,

docosahexaenoic acid or a salt or ester thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, or a mixture thereof.

25. The kit of any one of claims 18-24, further comprising milk.

26. The kit of claim 25, wherein the milk is selected from the group consisting of soy milk, human milk, cow milk, goat milk, oat milk, almond milk, rice milk, cashew milk, hemp milk, and coconut milk.

27. The kit of any one of claims 18-26, further comprising formula (e.g., baby or toddler formula).

28. The kit of claim 27, wherein the formula is selected from the group consisting of milk formula, dairy-free formula, soy-free formula, lactose-free formula, and vegan formula.

29. The kit of any one of claims 18-28, further comprising a sugar.

30. The kit of claim 29, wherein the sugar is selected from the group consisting of glucose, fructose, N-acetylglucosamine, galactose, sucrose, mannose, maltose, and lactose.

31. The kit of any one of claims 18-30, further comprising a bacteriophage selected from the group consisting of LH01 - Myoviridae, T4D - Myoviridae, LL12 - Myoviridae, LL5 - Siphorviridae , and PBC1.

32. The kit of any one of claims 18-31, further comprising urolithin A, urolithin B, or a mixture thereof.

33. A method for preparing a compound of formula (I): wherein Ri, R2, R3, R4, Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof; comprising:

(i) combining (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a second component comprising one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces, and

(ii) incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours.

34. The method of claim 33, wherein the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus (e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus ), Lactobacillus paracasei (e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum (e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02),

Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis (e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum (e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum (e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus .

35. The method of claim 33, wherein the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus , Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

36. The method of any one of claims 33-35, further comprising a step of adding a pharmaceutically acceptable carrier, excipient, binder or diluent following step (ii).

37. The method of any one of claims 33-36, wherein the ratio of the first component to the probiotic species is about 1:1 to 25:1 (w/w).

38. The method of any one of claims 33-37, wherein the probiotic species is at least 1 CFU (e.g., 1, 101, 102, 103, 104, 105, 106, 107, 108, 109, 1010, 1011, or 1012 CFU) per gram.

39. The method of any one of claims 33-38, wherein step (i) further comprises combining milk, fish oil, algal oil, chia seed oil, eicosapentaenoic acid or a salt or ester thereof,

docosahexaenoic acid or a salt or ester thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, a sugar, a bacteriophage or a mixture thereof with the first component and the one or more probiotic species.

40. The method of claim 39, wherein the milk is selected from the group consisting of soy milk, human milk, cow milk, goat milk, oat milk, almond milk, rice milk, cashew milk, hemp milk, and coconut milk.

41. The method of any one of claims 33-40, wherein step (i) further comprises combining formula (e.g., baby or toddler formula) with the first component and the one or more probiotic species.

42. The method of claim 41, wherein the formula is selected from the group consisting of milk formula, dairy-free formula, soy-free formula, lactose-free formula, and vegan formula.

43. The method of claim 39, wherein the sugar is selected from the group consisting of glucose, fructose, N-acetylglucosamine, galactose, sucrose, mannose, maltose, and lactose.

44. The method of claim 39, wherein the bacteriophage is selected from the group consisting of LH01 - Myoviridae, T4D - Myoviridae, LL12 - Myoviridae, LL5 - Siphorviridae , and PBC1.

45. The method of any one of claims 33-44, wherein Ri, R3, R4, Rs, R7, and Rs are each H, and R2 and R6 are each -OH.

46. The method of any one of claims 33-44, wherein Ri, R3, R4, Rs, R6, R7, and Rs are each H, and R2 is -OH.

47. A composition comprising a compound of formula (I):

wherein Ri, R2, R3, R4, Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof, prepared by the method of any one of claims 33-46.

48. The composition of claim 47, wherein the composition is in the form of a food product or a dietary supplement.

49. A method of treating or preventing a mitochondrial disease or condition, the method comprising administering to a subject in need thereof the composition of any one of the claims 1- 17 or 47-48.

50. The method of claim 49, wherein the disease is selected from the group consisting of aging, diabetes, obesity and neurodegenerative disease.

51. A method of maintaining or enhancing metabolic rate, the method comprising

administering to a subject the composition of any one of the claims 1-17 or 47-48.

52. A method of enhancing or maintaining muscle growth or performance, the method comprising administering to a subject the composition of any one of the claims 1-17 or 47-48.

53. A method of extending lifespan, the method comprising administering to a subject the composition of any one of the claims 1-17 or 47-48.

54. The method of any one of claims 49-53, wherein the administration is oral.

55. A composition comprising:

(a) a frst component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a prebiotic component.

56. The composition of claim 55, wherein the prebiotic component comprises prebiotic fiber.

57. The composition of claim 56, wherein the prebiotic fiber is obtained from one or more of bananas, onions, garlic, Jerusalem artichoke, apples, chicory root, oatmeal, asparagus, dandelion greens, barley and beans.

58. The composition of claim 55, wherein the prebiotic component comprises kefir.

59. A method for preparing a compound of formula (I):

wherein Ri, R2, R3, R4, Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof; comprising:

(i) combining (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a prebiotic component, and (ii) incubating the resulting combination of step (i) a temperature of at least 20 °C for at least 8 hours.

60. The method of claim 59, wherein the prebiotic component comprises prebiotic fiber.

61. The method of claim 60, wherein the prebiotic fiber is obtained from one or more of bananas, onions, garlic, Jerusalem artichoke, apples, chicory root, oatmeal, asparagus, dandelion greens, barley and beans.

62. The method of claim 59, wherein the prebiotic component comprises kefir.

Description:
COMPOSITIONS AND METHODS FOR BIOSYNTHETIC PREPARATION OF UROLITHIN COMPOUNDS AND USE THEREOF

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of US provisional application US 62/664,752, filed April 30, 2018, which is hereby incorporated by reference in its entirety.

FIELD

[0002] The present disclosure relates generally to compositions and methods for the biosynthetic preparation of urolithin compounds and the use of biosynthesized urolithins for treatment and prevention of mitochondrial diseases and conditions.

BACKGROUND

[0003] Urolithins are substituted dibenzopyran-6-one derivatives that can be produced from ellagic acid metabolism by gut microbiota. Urolithins have been shown to have antioxidant, anticancer and anti-inflammatory properties. Urolithins are not found in common food sources, and their bioavailability largely depends on a strong inter-individual variability in microbiota compositions affecting urolithin productions. Chemical synthesis of urolithin compounds has been described. See, e.g., US 9,573,922. However, a robust and cost-effective biosynthetic method for producing large scales of urolithins is still lacking.

[0004] This application meets such a need by providing compositions and methods for making urolithin compounds biosynthetically from metabolic precursors and probiotic bacteria. Also provided are methods of using biosynthesized urolithins for treating and preventing mitochondrial diseases or conditions.

BRIEF SUMMARY

[0005] Provided herein is a composition comprising:

(a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a second component comprising one or more probiotic species.

[0006] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g. ,

Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g. , Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium

pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0007] In some embodiments, the composition further comprises a lipid. In some embodiments, the lipid is selected from the group consisting of fish oil or a salt thereof, algal oil, chia seed oil, black cumin oil, red grape seed oil, red raspberry seed oil, cranberry seed oil, pumpkin seed oil, eicosapentaenoic acid or a salt or ester thereof, docosahexaenoic acid or a salt or ester thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, and a mixture thereof. In some embodiments, the composition further comprises milk. In some embodiments, the milk is selected form the group consisting of human milk, cow milk, goat milk, oat milk, rice milk, almond milk, cashew milk, flax milk, and coconut milk. In some embodiments, the composition further comprises a sugar, including, without limitation, glucose, fructose, N- ace tylglucos amine, galactose, sucrose, mannose, maltose, or lactose. In some embodiments, the composition further comprises a bacteriophage, including, without limitation, Myoviridae {e.g., LH01 - Myoviridae, T4D - Myoviridae , and LL12 - Myoviridae), Siphorviridae {e.g., LL5 - Siphorviridae) or Bacteriophage PBC1.

[0008] Also provided herein is a kit comprising: (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a second component comprising one or more probiotic species.

[0009] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g. ,

Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g. , Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium

pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0010] In some embodiments, the kit further comprises a lipid. In some embodiments, the lipid is selected from the group consisting of fish oil or a salt thereof, algal oil, chia seed oil, black cumin oil, red grape seed oil, red raspberry seed oil, cranberry seed oil, pumpkin seed oil, eicosapentaenoic acid or a salt or ester thereof, docosahexaenoic acid or a salt or ester thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, and a mixture thereof. In some embodiments, the kit further comprises milk. In some embodiments, the milk is selected form the group consisting of human milk, cow milk, goat milk, oat milk, rice milk, almond milk, cashew milk, flax milk, and coconut milk. In some embodiments, the kit further comprises glucose, including, without limitation, glucose, fructose, N-acetylglucosamine, galactose, sucrose, mannose, maltose, or lactose. In some embodiments, the kit further comprises a bacteriophage, including, without limitation, Myoviridae (e.g., LH01 - Myoviridae, T4D - Myoviridae, and LL12 - Myoviridae),

Siphorviridae (e.g., LL5 - Siphorviridae), or Bacteriophage PBC1.

[0011] Also provided here is a method for preparing a compound of formula (I):

wherein Ri, R2, R3, R 4 , Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof; comprising:

(i) combining (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a second component comprising one or more probiotic species, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours.

[0012] In some embodiments, the first component and the probiotic species is about 1:1 to 25:1 (w/w). In some embodiments, step (i) further comprises combining milk, fish oil, algal oil, chia seed oil, eicosapentaenoic acid, docosahexaenoic acid, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, glucose, a bacteriophage, or a mixture thereof with the first component and the one or more probiotic species. In some embodiments, Ri, R 3 , R 4 , Rs, R7 , and Re are each H, and R2 and Re are each -OH. In some embodiments, Ri, R3, R 4 , Rs, R6, R7, and Re are each H, and R2 is -OH. [0013] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g. ,

Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g. , Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium

pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0014] In another aspect, also provided here is a composition comprising a compound of formula (I):

wherein Ri, R2, R3, R4, Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof, wherein the composition is prepared by (i) combining (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a second component comprising one or more probiotic species, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours.

[0015] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g. ,

Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g. , Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium

pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0016] In another aspect, also provided herein are methods for treating or preventing a mitochondrial disease or condition comprising administering to a subject in need thereof any of the compositions described herein. In another aspect, also provided herein are methods for enhancing metabolic rate comprising administering to a subject in need thereof any of the compositions described herein. In another aspect, also provided herein are methods for enhancing or maintaining muscle growth or performance comprising administering to a subject in need thereof any of the compositions described herein. In another aspect, also provided herein are methods for extending lifespan comprising administering to a subject in need thereof any of the compositions described herein.

[0017] In another aspect, also provided herein are composition comprising: (a) a frst component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a prebiotic component. In another aspect, also provided herein are methods for preparing a compound of formula (I):

wherein Ri, R2, R3, R4, Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof; comprising: (i) combining (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a prebiotic component, and (ii) incubating the resulting combination of step (i) a temperature of at least 20 °C for at least 8 hours.

DETAILED DESCRIPTION

[0018] The following description is presented to enable a person of ordinary skill in the art to make and use the various embodiments. Descriptions of specific compositions, techniques, and applications are provided only as examples. Various modifications to the examples described herein will be readily apparent to those of ordinary skill in the art, and the general principles defined herein may be applied to other examples and applications without departing from the spirit and scope of the various embodiments. Thus, the various embodiments are not intended to be limited to the examples described herein and shown, but are to be accorded the scope consistent with the claims. [0019] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents, applications, published applications and other publications referred to herein are incorporated by reference in their entireties. If a definition set forth in this section is contrary to or otherwise inconsistent with a definition set forth in a patent, application, or other publication that is herein incorporated by reference, the definition set forth in this section prevails over the definition incorporated herein by reference.

[0020] As used herein and in the appended claims, the singular forms“a,”“an,” and“the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as“solely,”

“only” and the like in connection with the recitation of claim elements, or use of a“negative” limitation.

[0021] As used herein, the terms“including,”“containing,” and“comprising” are used in their open, non-limiting sense.

[0022] To provide a more concise description, some of the quantitative expressions given herein are not qualified with the term“about.” It is understood that, whether the term“about” is used explicitly or not, every quantity given herein is meant to refer to the actual given value, and it is also meant to refer to the approximation to such given value that would reasonably be inferred based on the ordinary skill in the art, including equivalents and approximations due to the experimental and/or measurement conditions for such given value.

[0023] Except as otherwise noted, the methods and techniques of the present

embodiments are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification.

[0024] It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. All combinations of the embodiments pertaining to particular method steps, reagents, or conditions are specifically embraced by the present disclosure and are disclosed herein just as if each and every combination was individually and explicitly disclosed.

[0025] A“pharmaceutically acceptable salt” is a salt form that is non-toxic, biologically tolerable, or otherwise biologically suitable for administration to the subject. See generally Berge et al. (1977) J. Pharm. Sci. 66, 1-19. Particular pharmaceutically acceptable salts are those that are pharmacologically effective and suitable for contact with the tissues of subjects without undue toxicity, irritation, or allergic response.

Biosynthetic Preparation of Urolithin Compounds

[0026] In one aspect, the present disclosure relates to a biosynthetic method for preparing urolithin compounds. Urolithins are substituted dibenzopyran-6-one derivatives that are produced from ellagic acid metabolism by gut microbiota. Cerda et al. (2005) J. Agric. Food Chem. 53, 5571. Urolithins have been shown to have antioxidant, anticancer and anti inflammatory properties. For example, urolithins exhibited potent antioxidant properties compared with those of ascorbic acid and some of their precursors. Bialonska et al. (2009) J. Agric. Food Chem. 57, 10181; Larrosa et al. (2010) J. Nutri. Biochem. 21, 717. Urolithins were also able to induce apoptosis of human colon cancer cells at 25-50 mM. Kasimsetty et al. (2010) J. Agric. Food Chem. 58, 2180. Recently, UA has been shown to induce mitophagy and prolong lifespan in C. elegans. Ryu et al. (2016) Nat. Med. 22, 879.

[0027] Urolithins are not commonly found in nature but they have been found in plants with high contents of ellagitannins, such as Tamarix nilotica and Punica granatum. A strong inter-individual variability has been observed in microbiota composition affecting urolithin production. Cerda et al. (2005). Urolithins start to appear in plasma 6-8 hours after consumption of ellagitannins or ellagic acid-rich foods, suggesting its production in colon. Cerda et al. (2004) Euro. J. Nutrition 43, 205. Urolithins can also be synthesized chemically. See e.g., US 9573922. Provided herein is a reliable and cost-effective method for preparing urolithin compounds biosynthetically.

[0028] Described herein is a method for preparing a compound of formula (I): wherein Ri, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof; comprising:

(i) combining (a) a first component selected from the group consisting of pomegranate extract, pomegranate juice, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a second component comprising one or more probiotic species, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours.

[0029] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g.,

Lactobacillus acidophilus La- 14 and Lactobacillus acidophilus LA85), Lactobacillus plantarum {e.g., Lactobacillus plantarum Lp90), Lactobacillus rhamnosus {e.g.,

Lactobacillus rhamnosus Lr-32 and Lactobacillus rhamnosus LRa05), Lactobacillus reuteri {e.g., Lactobacillus reuteri LR08), Lactobacillus casei {e.g., Lactobacillus casei LC89), Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius {e.g. ^

Lactobacillus salivarius LS97). Lactobacillus fermentum {e.g., Lactobacillus fermentum LF15), Lactobacillus crispatus {e.g. , Lactobacillus crispatus LCr86), Bifidobacterium bifidum (e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis (e.g.,

Bifidobacterium lactis Bl-04), Bifidobacterium longum (e.g. , Bifidobacterium longum Bl-05, B. longum BL21 and B. longum infantis BI45), Bifidobacterium pseudocatenulatum (e.g., Bifidobacterium pseudocatenulatum INIA P815), Ellagibacter isourolithinifaciens (e.g., Ellagibacter isourolithinifaciens DSM 104140), Enterorhabdus musicola DSM 19490 (e.g., Enterorhabdus musicola DSM 19490), Enterorhabdus caecimuris (e.g., Enterorhabdus caecimuris DSM 21839), Adlercreutzia equolifaciens (e.g., Adlercreutzia equolifaciens DSM 19450), Asaccharobacter celatus (e.g., Asaccharobacter celatus DSM 18785), Parvibacter caecicola (e.g. , Parvibacter caecicola DSM 22242), Gordonibacter urolithinfaciens (CEB AS 1/15P), Gordonibacter pamelaeae (e.g., Gordonibacter pamelaeae 7-lO-l-b) and

Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0030] In one aspect, the disclosure relates to a method for preparing a compound of formula (I):

wherein Ri, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof; comprising:

(i) combining (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a second component comprising one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri,

Bifidobacterium pseudocatenulatum and Bifidobacterium breve, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours.

First Component

[0031] The first component of the combination is selected from the group consisting of pomegranate extract, pomegranate juice, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof.

[0032] Pomegranate fruits are a rich source of natural products that are beneficial to the health of human and animals, including polyphenols, most of which are ellagitannins.

Pomegranate extracts have been produced in both dry and liquid forms to provide alternative sources for obtaining these natural products in pomegranate fruits, in addition to pomegranate juice. Studies have suggested that pomegranate extracts incorporate major polyphenols from the fruits and provide similar bioavailability of ellagitannin metabolites in plasma and urine in comparison to pomegranate juice. Seeram et al. (2008) J. Med. Food 11, 390.

Pomegranate extract has been shown to exert antioxidant, anticancer, and anti-inflammatory activities. See e. g. , Singh et al. (2002) J. Agric. Food Chem. 50, 81; Negi et al. (2003) Food Chem. 80, 393; Lansky et al. (2006) J. Ethnopharmacology.

[0033] Pomegranate extract can be produced in both dry and liquid forms. The liquid form may be a liquid concentrated extract that is produced by the extraction of the fruit residue obtained after pressing of the pomegranate fruits for juice. Extraction may be performed using pressed pomegranate fruit skins, pulp, seeds, peel, rind, and/or arils. The dry form may be obtained from the liquid concentrate by a solid phase extraction and contains a high content of polyphenols, including ellagitannins and ellagic acids that can be both free and oligomeric.

[0034] In some embodiments, each ounce of the liquid form pomegranate extract may contain an amount of polyphenol measured in gallic acid equivalents at greater than about 10 mg, greater than about 20 mg, greater than about 30 mg, greater than about 40 mg, greater than about 50 mg, greater than about 60 mg, greater than about 70 mg, greater than about 80 mg, greater than about 90 mg, greater than about 100 mg, greater than about 110 mg, greater than about 120 mg, greater than about 130 mg, greater than about 140 mg, greater than about 150 mg, greater than about 160 mg, greater than about 170 mg, greater than about 180 mg, greater than about 190 mg, greater than about 200 mg, greater than about 250 mg, greater than about 300 mg, greater than about 350 mg, greater than about 400 mg, greater than about 450 mg, or greater than about 500 mg. In some embodiments, each ounce of the liquid form pomegranate extract may contain an amount of polyphenol measured in gallic acid equivalents at about 10 mg to about 20 mg, about 20 mg to about 30 mg, about 30 mg to about 40 mg, about 40 mg to about 50 mg, about 50 mg to about 60 mg, about 60 mg to about 70 mg, about 70 mg to about 80 mg, about 80 mg to about 90 mg, about 90 mg to about 100 mg, about 100 mg to about 110 mg, about 110 mg to about 120 mg, about 120 mg to about 130 mg, about 130 mg to about 140 mg, about 140 mg to about 150 mg, about 150 mg to about 160 mg, about 160 mg to about 170 mg, about 170 mg to about 180 mg, about 180 mg to about 190 mg, about 190 mg to about 200 mg, about 210 mg to about 250 mg, about 250 mg to about 300 mg, about 300 mg to about 400 mg, about 400 mg to about 450 mg, about 450 mg to about 500 mg, about 10 mg to about 100 mg, about 100 mg to about 200 mg, about 200 mg to about 300 mg, about 300 mg to about 400 mg, or about 400 mg to about 500 mg.

[0035] In some embodiments, each gram of the dry form pomegranate extract may contain an amount of polyphenol measured in gallic acid equivalents at greater than about 100 mg, greater than about 150 mg, greater than about 200 mg, greater than about 250 mg, greater than about 300 mg, greater than about 350 mg, greater than about 400 mg, greater than about 450 mg, greater than about 500 mg, greater than about 550 mg, greater than about 600 mg, greater than about 650 mg, greater than about 700 mg, greater than about 750 mg, greater than about 800 mg, greater than about 850 mg, greater than about 900 mg, or greater than about 950 mg. In some embodiments, each gram of the dry form pomegranate extract may contain an amount of polyphenol measured in gallic acid equivalents at about 100 mg to about 150 mg, about 150 mg to about 200 mg, about 200 mg to about 250 mg, about 250 mg to about 300 mg, about 300 mg to about 350 mg, about 350 mg to about 400 mg, about 400 mg to about 450 mg, about 450 mg to about 500 mg, about 500 mg to about 550 mg, about 550 mg to about 600 mg, about 600 mg to about 650 mg, about 650 mg to about 700 mg, about 700 mg to about 750 mg, about 750 mg to about 800 mg, about 800 mg to about 850 mg, about 850 mg to about 900 mg, or about 900 mg to about 950 mg.

[0036] In one aspect, the pomegranate extract may contain both liquid and dry forms. In some embodiments, the dry form provides an amount of polyphenol measured in gallic acid equivalents at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% of the total polyphenol content in the pomegranate extract. In some embodiments, the dry form provides an amount of polyphenol measured in gallic acid equivalents at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% of the total polyphenol content in the pomegranate extract.

[0037] In some embodiments, the liquid form provides an amount of polyphenol measured in gallic acid equivalents at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% of the total polyphenol content in the pomegranate extract. In some embodiments, the liquid form provides an amount of polyphenol measured in gallic acid equivalents at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% of the total polyphenol content in the pomegranate extract.

[0038] In another aspect, the pomegranate extract may contain added polyphenols after the extraction processes from the pomegranate fruit. Added polyphenols may include, without limitation, ellagitannins, ellagic acids, and other flavonoids, such as quercetin, kaempferol, and luteolin glycosides. In some embodiments, the added polyphenols provide an amount of polyphenol measured in gallic acid equivalents at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% of the total polyphenol content in the pomegranate extract. In some embodiments, the added polyphenols provide an amount of polyphenol measured in gallic acid equivalents at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% of the total polyphenol content in the pomegranate extract.

[0039] In another aspect, the pomegranate extract comprises ellagic acid at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% of the weight of the pomegranate extract.

[0040] Ellagitannins are polyphenols that can be found in fruits, nuts and seeds, such as strawberries, raspberries, pomegranates, walnuts, pecans, and blackberries. Particularly, pomegranate juice produced by squeezing the whole fruit has been shown to have the highest concentration of ellagitannins relative to other commonly consumed juices. Pomegranate juice has presented potent antioxidant properties and anticancer effects that are usually attributed to its high polyphenol content. See e.g., Afaq et al. (2005) hit. J. Cancer 113, 423; Seeram et al. (2005) J. Nutr. Biochem. 16, 360; Adams et al. (2006) J. Agric. Food Chem. 54, 980; Malik et al. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 14813; Adams et al. (2010)

Cancer Prev. Res. 3, 108. Punicalagin is the largest ellagitannin in pomegranate juice, having a molecular weight of >1000 g/mol and responsible for at least half of the antioxidant property of the juice. In addition to pomegranate juice, pomegranate extract or concentrate also contains high levels of ellagitannins. [0041] Ellagitannins that may be used in the compositions and methods described herein include, without limitation, castalagin, castalin, casuarictin, grandinin, roburin A, tellimagrandin II, terflavin B, vescalagin, punicacortein A, punicacortein B, punicacortein C, punicacortein D, punicafolin, punigluconin, punicalagin, pedunculagin, punicalin, granatin A, granatin B, 5-O-galloylpunicacortein D, 2-O-galloylpunicalin, casuarinin, gallagyldilactone, corilagin, and strictinin.

[0042] Ellagic acid is found in more than 700 species of higher plants, including plants of the genus Alnus (Betulaceae), Betula (Betulaceae), Juglans (Juglandaceae), Castanea (Fagaceae), and Quercus (Fagaceae). Ellagic acid has also been extracted from berries (e.g., cranberry, raspberry and strawberry), pears, peaches, plums, grapes, apples, kiwi, pomegranate, and several nuts (e.g., walnut and pecan). Ellagic acid can also be extracted from distilled beverages. Mostly, these plants produce ellagic acid from hydrolysis of tannins such as ellagitannins. The content of ellagic acid in these plants vary by plant species and varieties, and can be strongly influenced by climatic and weather conditions. For example, seasonal fluctuation of ellagic acid content associated with photoperiodism and temperature conditions has been observed. A method for producing ellagic acid with a high percentage yield has been reported and is based on treatment of an aqueous solution of the Chinese gallotannin with concentrated alkali and sodium bicarbonate, followed by aeration with air or oxygen. Ukrainian No. 23109A.

Ellagic acid

[0043] Ellagic acid has a wide and diverse spectrum of biological activities. In addition to its antioxidant activity, ellagic acid has demonstrated antihypertensive, anticancer, anti viral and anti-inflammatory properties. See e.g., Berkeban et al. (2015) Nutrients 7, 5256; Umesalma et al. (2011) Eur. J. Pharmacol. 660, 249; Han et al. (2006) Anticancer Res. 26, 3601; Cornelio et al. (2013) Mediat. Inflamm. 2013, 164202; Nonaca et al. (1990) Chem. Pharm. Bull. 38, 2151. [0044] In another aspect, the first component is a salt of an ellagitannin and/or a salt of ellagic acid. In some embodiments, the salt is a pharmaceutically acceptable salt. In some embodiments, pharmaceutically acceptable salts include, without limitation, acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, oxalic acid, propionic acid, succinic acid, maleic acid, tartaric acid and the like. These salts may be derived from inorganic or organic acids. Non-limiting examples of pharmaceutically acceptable salts include, without limitation, sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen-phosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-l,4-dioates, hexyne-l,6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, methylsulfonates, propylsulfonates, besylates, xylenesulfonates, naphthalene- 1 -sulfonates, naphthalene-2-sulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, g-hydroxybutyrates, glycolates, tartrates, and mandelates. In some embodiments, pharmaceutically acceptable salts are formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base. Salts derived from pharmaceutically acceptable organic non-toxic bases include, without limitation, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-diethylaminoethanol, tromethamine, trimethamine, dicyclohexylamine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, N- ethylglucamine, N-methylgluc amine, theobromine, purines, piperazine, piperidine, N- ethylpiperidine, polyamine resins, amino acids such as lysine, arginine, histidine, and the like. Examples of pharmaceutically acceptable base addition salts include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. In some

embodiments, the organic non-toxic bases are I, -amino acids, such as L-lysine and L- arginine, tromethamine, N-ethylglucamine and N-methylgluc amine. Acceptable inorganic bases include, without limitation, aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, and the like. Lists of other suitable pharmaceutically acceptable salts are found in Remington's Pharmaceutical Sciences, l7th Edition, Mack Publishing Company, Easton, Pa., 1985.

[0045] In another aspect, the first component comprises a mixture of pomegranate extract, an ellagitannin or a salt thereof, or ellagic acid or a salt thereof. In some

embodiments, the first component comprises one or more ellagitannins and ellagic acid. In some embodiments, the first component comprises one or more ellagitannins. In some embodiments, the first component comprises one or more ellagitannins and pomegranate extract. In some embodiments, the first component comprises one or more ellagitannins and pomegranate extract. In some embodiments, the first component comprises ellagic acid and pomegranate extract. In some embodiments, the first component comprises one or more urolithins. In some embodiments, the first component comprises one or more ellagitannins, ellagic acid, and pomegranate extract. In some embodiments, the first component comprises punicalagin and ellagic acid. In some embodiments, the first component comprises punicalagin and pomegranate extract. In some embodiments, the first component comprises punicalagin, pomegranate extract, and ellagic acid.

[0046] In some embodiments, the first component comprises salts of one or more ellagitannins and ellagic acid. In some embodiments, the first component comprises salts of one or more ellagitannins. In some embodiments, the first component comprises salts of one or more ellagitannins and pomegranate extract. In some embodiments, the first component comprises salts of ellagic acid and pomegranate extract. In some embodiments, the first component comprises salts of one or more ellagitannins, ellagic acid, and pomegranate extract. In some embodiments, the first component comprises salts of punicalagin and ellagic acid. In some embodiments, the first component comprises salts of punicalagin and one or pomegranate extract. In some embodiments, the first component comprises salts of punicalagin, ellagic acid, and pomegranate extract. In some embodiments, pomegranate juice may be used in addition to or as an alternative to pomegranate extract.

[0047] In another aspect, the first component is in the form of a food product or a dietary supplement.

Second Component

[0048] The second component of the combination is one or more probiotic species. Probiotics are live microorganisms that can confer health benefits to humans and animals, when administered in adequate amounts. Probiotics can be found in fermented dairy products, probiotic fortified foods, and in freeze-dried form. Different strains of probiotic bacteria may exert different effects based on specific capabilities and enzymatic activities, even within one species. Mechanisms of action by which probiotic achieve their beneficial actions have not been fully understood, and several known or postulated mechanisms include, without limitation, bioconversion, reduction of inflammation, simulation of innate immune response, competitive exclusion for binding sites, and production of growth substrates.

[0049] Common probiotic microorganisms include, but are not limited to, Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus and Saccharomyces. Lactobacillus is one of the most common probiotics found in the human digestive tract (e.g., gastrointestinal tract) and genitourinary tract. Lactobacillus is also found in food, such as yogurt. Various Lactobacillus species are used for controlled fermentation in food production, such as yogurt, kimchi, cider, beer, and pickles. They are also used for treating diarrhea, vaginal infections and skin disorders. Lactobacillus plantarum is a widespread member of Lactobacillus genus, which has the versatile ability to grow at any pH level of 3.2 or higher and at any temperature between 15 and 45 °C. In addition to food production, Lactobacillus plantarum has also shown efficacy toward treating irritable bowel syndrome and ulcerative colitis. See e.g. , Niedzielin et al. (2001) Eur. J. Gastroenterology & Hepatology 13, 1143; Venturi et al.

(1999) Alimentary Pharmcol. & Ther 13, 1103. Lactobacillus rhamnosus is a gram-positive heterofermentative facultative anaerobic rod that is commonly found in the healthy female genito-urinary tract. Lactobacillus rhamnosus GG strain has been extensively investigated for its health benefits including treating acute gastroenteritis, atopic dermatitis, urogenital tract infection, and anxiety. See e.g., Gruber et al. (2007) Allergy 62, 1270; Sindhu et al. (2014) Clin. Infect. Dis. 58, 1107. Lactobacillus reuteri is a gram-positive bacterium that inhibits the gut of mammals and birds, and can produce reuterin, reutericin 6, and

reutericyclin. Lactobacillus acidophilus occurs naturally in the human body, especially in the digestive tract (e.g., gastrointestinal tract) and mouth. It can ferment sugars into lactic acid and grows in relatively low pH conditions. Some of these strains have probiotic features and are commercially used in dairy products, such as yogurts and milk. The growth of

Lactobacillus acidophilus is complemented by Lactobacillus casei, another commercial probiotic. Beverages containing certain strains of Lactobacillus casei have been shown to improve digestion, increase immunity, and improve cholesterol levels. Lactobacillus salivarius is another species that is commonly found in the human digestive tract (e.g., gastrointestinal tract) and mouth. Thanks to its rapid growth, Lactobacillus salivarius suppresses pathogenic bacteria. Lactobacillus bulgaricus is one of the first probiotic species ever investigated, and it is one of the main bacteria used for yogurt production. It survives gastrointestinal transit of a healthy human consuming yogurt. Mater et al. (2005) FEMS Microbiol. Lett. 250, 185. Lactobacillus paracasei strains can be found in dairy, plants and human and animal digestive tracts (e.g., gastrointestinal tract). Their fermentative properties make them suitable for processing food and dietary supplements. Felten et al. (1999) J.

Clinical Microbiol. 37, 729.

[0050] Bifidobacterium is one of the major bacteria genus that make up the colon microbiota in mammals. Various species can be found in the digestive tract (e.g., gastrointestinal tract), vagina, and mouth of mammals. Bacteria in this genus produce lactic and acetic acids as byproducts of glucose utilization. Bifidobacterium infantis has shown to alleviate symptoms of irritable bowel syndrome and lower inflammation levels. See e.g. , Clarke et al. (2012) Alimentary Pharmcol. & Ther. 35, 403; Osman et al. (2006) BMC Gastroenterology 6, 31. Bifidobacterium breve can be found in feces of human infants and can ferment mannitol and sorbitol. Studies have also shown that Bifidobacterium breve exerts preventive effects on relapse of ulcerative colitis. See e.g. , Ishikawa et al. (2013) J. Amer. Col. Nutri. 22, 56. Bifidobacterium lactis is commonly found in raw milk and can also inhabit human digestive tracts (e.g., gastrointestinal tract). In addition to being used as starter culture for buttermilk and cheese, Bifidobacterium lactis supports healthy cholesterol levels and digestion of sugars and fibers. Lack of Bifidobacterium bifidum has been associated with Candida infection in humans, as it competes with overgrowth of Candida and yeast.

Bifidobacterium bifidum reduces the chance of acute diarrhea and helps maintain vaginal homeostasis. Bifidobacterium longum has a significant presence in an infant’s digestive tract (e.g., gastrointestinal tract), and decreases gradually as the host ages. It has been shown to be useful in treating ulcerative colitis in combination with conventional therapies.

[0051] Streptococcus is a genus of gram-positive bacteria that grow in chains or pairs.

For decades, Streptococcus thermophilus has been used to make yogurts, along with

Lactobacillus bulgaricus. These two species may have synergistic effects during the production process.

[0052] Akkermansia muciniphila is a gram-negative, oval-shaped bacterium. It has been recently discovered and commonly found in the digestive tract (e.g., gastrointestinal tract) of a number of animal species, including humans, and shown to lower inflammation levels in irritable bowel syndrome. Van Passel et al. (2011) PloS ONE 6, el6876. Akkermansia muciniphila requires a protein source and a sugar source, including, without limitation, glucose, fructose, N-acetylglucosamine, galactose, sucrose, maltose, or lactose.

[0053] In one aspect, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus,

Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g. ,

Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g. , Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium

pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0054] In some embodiments, the second component comprises a mixture of

Akkermansia muciniphila, Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc- 37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilu . In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus (e.g., Lactobacillus acidophilus La-l4), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Bifidobacterium bifidum {e.g. , Bifidobacterium bifidum Bb-02,

Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium lactis {e.g. , Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum {e.g. , Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Akkermansia muciniphila, Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La-l4), Lactobacillus plantarum, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus casei. In some embodiments, the second component comprises a mixture of Lactobacillus casei, Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus, and Lactobacillus acidophilus. In some embodiments, the second component comprises a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii {e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus rhamnosus, and Bifidobacterium bifidum. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus La-l4, Bifidobacterium lactis Bl-04, Lactobacillus paracasei Lpc-37,

Lactobacillus rhamnosus Lr-32, Bifidobacterium bifidum/lactis Bb-02, Bifidobacterium pseudocatenulatum INIA P815 and Bifidobacterium longum Bl-05. In some embodiments, the second component comprises one or more of Ellagibacter isourolithinifaciens {e.g., Ellagibacter isourolithinifaciens DSM 104140), Enterorhabdus musicola DSM 19490 {e.g., Enterorhabdus musicola DSM 19490), Enterorhabdus caecimuris {e.g., Enterorhabdus caecimuris DSM 21839), Adlercreutzia equolifaciens {e.g., Adlercreutzia equolifaciens DSM 19450), Asaccharobacter celatus {e.g., Asaccharobacter celatus DSM 18785), Parvibacter caecicola {e.g., Parvibacter caecicola DSM 22242), Gordonibacter urolithinfaciens (CEB AS 1/15P) and Gordonibacter pamelaeae {e.g., Gordonibacter pamelaeae 7-lO-l-b). [0055] In some embodiments, the second component comprises a mixture of

Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the second component comprises Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the second component comprises Akkermansia muciniphila and Bifidobacterium infantis. In some embodiments, the second component comprises Akkermansia muciniphila and Lactobacillus plantarum. In some embodiments, the second component is Akkermansia muciniphila and Lactobacillus rhamnosus. In some embodiments, the second component comprises Akkermansia muciniphila and Lactobacillus reuteri. In some embodiments, the second component comprises Akkermansia muciniphila and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus acidophilus and Bifidobacterium infantis. In some embodiments, the second component comprises Lactobacillus acidophilus and Lactobacillus plantarum. In some embodiments, the second component comprises

Lactobacillus acidophilus and Lactobacillus rhamnosus. In some embodiments, the second component comprises Lactobacillus acidophilus and Lactobacillus reuteri. In some embodiments, the second component comprises Lactobacillus acidophilus and

Bifidobacterium breve. In some embodiments, the second component comprises

Bifidobacterium infantis and Lactobacillus plantarum. In some embodiments, the second component comprises Bifidobacterium infantis and Lactobacillus rhamnosus. In some embodiments, the second component comprises Bifidobacterium infantis and Lactobacillus reuteri. In some embodiments, the second component comprises Bifidobacterium infantis and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus plantarum and Lactobacillus rhamnosus. In some embodiments, the second component comprises Lactobacillus plantarum and Lactobacillus reuteri. In some embodiments, the second component comprises Lactobacillus plantarum and

Bifidobacterium breve. In some embodiments, the second component comprises

Lactobacillus reuteri and Bifidobacterium breve. In some embodiments, the second component is Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the second component comprises Bifidobacterium infantis,

Bifidobacterium pseudocatenulatum, Bifidobacterium breve and Lactobacillus acidophilus. In some embodiments, the second component comprises Akkermansia muciniphila,

Bifidobacterium infantis, Bifidobacterium breve and Lactobacillus acidophilus. In some embodiments, the second component comprises Akkermansia muciniphila, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the second component comprises Bifidobacterium infantis, Lactobacillus plantarum,

Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus plantarum, Lactobacillus rhamnosus,

Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium infantis. In some embodiments, the second component comprises Akkermansia muciniphila,

Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0056] In another aspect, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus casei. In another aspect, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus acidophilus La- 14, Bifidobacterium lactis Bl-04, Lactobacillus paracasei Lpc- 37, Lactobacillus rhamnosus Lr-32, Bifidobacterium bifidum/lactis Bb-02, Bifidobacterium pseudocatenulatum INIA P815 and Bifidobacterium longum Bl-05. In another aspect, the second component comprises one or more probiotic species selected from the group consisting of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus bulgaricus, Lactobacillus rhamnosusi, and Bifidobacterium bifidum. In yet another aspect, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus casei, Lactobacillus bulgaricus, Bifidobacterium longum, Streptococcus thermophilus, Bifidobacterium pseudocatenulatum and Lactobacillus acidophilus.

[0057] In another aspect, the second component is in the form of a food product or dietary supplement. In some embodiments, the second component is in the form of a yogurt.

[0058] In another aspect, the one or more probiotic species of the second component are present at greater than 1 cell, greater than about 1 CFU/gram, greater than about 5 CFU/gram, greater than about 10 CFU/gram, greater than about 50 CFU/gram, greater than about 100 CFU/gram, greater than about 500 CFU/gram, greater than about 1,000 CFU/gram, greater than about 5,000 CFU/gram, greater than about 10,000 CFU/gram, greater than about 50,000 CFU/gram, greater than about 100,000 CFU/gram, greater than about 500,000 CFU/gram, greater than about 1 million CFU/gram, greater than about 50 million CFU/gram, greater than about 100 million CFU/gram, greater than about 150 million CFU/gram, greater than about 200 million CFU/gram, greater than about 250 million CFU/gram, greater than about 300 million CFU/gram, greater than about 350 million CFU/gram, greater than about 400 million CFU/gram, greater than about 450 million CFU/gram, greater than about 500 million CFU/gram, greater than about 550 million CFU/gram, greater than about 600 million CFU/gram, greater than about 650 million CFU/gram, greater than about 700 million CFU/gram, greater than about 750 million CFU/gram, greater than about 800 million CFU/gram, greater than about 850 million CFU/gram, greater than about 900 million CFU/gram, greater than about 950 million CFU/gram, greater than about 1 billion CFU/gram, greater than about 2 billion CFU/gram, greater than about 3 billion CFU/gram, greater than about 4 billion CFU/gram, greater than about 5 billion CFU/gram, greater than about 6 billion CFU/gram, greater than about 7 billion CFU/gram, greater than about 8 billion CFU/gram, greater than about 9 billion CFU/gram, greater than about 10 billion CFU/gram, greater than about 20 billion CFU/gram, greater than about 30 billion CFU/gram, greater than about 40 billion CFU/gram, or greater than about 50 billion CFU/gram at the time of manufacture. In some embodiments, the one or more probiotic species in the second component are present at about 1 CFU/gram to about 100 CFU/gram, about 100 CFU/gram to about 1,000 CFU/gram, about 1,000 CFU/gram to about 10,000 CFU/gram, about 10,000 CFU/gram to about 100,000 CFU/gram, about 100,000 CFU/gram to about 1 million CFU/gram, about 1 million

CFU/gram to about 100 million CFU/gram, about 100 million CFU/gram to about 200 million CFU/gram, about 200 million CFU/gram to about 300 million CFU/gram, about 300 million CFU/gram to about 400 million CFU/gram, about 400 million CFU/gram to about 500 million CFU/gram, about 500 million CFU/gram to about 600 million CFU/gram, about 600 million CFU/gram to about 700 million CFU/gram, about 700 million CFU/gram to about 800 million CFU/gram, about 800 million CFU/gram to about 900 million CFU/gram, about 900 million CFU/gram to about 1 billion CFU/gram, about 1 billion CFU/gram to about 2 billion CFU/gram, about 2 billion CFU/gram to about 3 billion CFU/gram, about 3 billion CFU/gram to about 4 billion CFU/gram, about 4 billion CFU/gram to about 5 billion CFU/gram, about 5 billion CFU/gram to about 6 billion CFU/gram, about 6 billion

CFU/gram to about 7 billion CFU/gram, about 7 billion CFU/gram to about 8 billion

CFU/gram, about 8 billion CFU/gram to about 9 billion CFU/gram, about 9 billion

CFU/gram to about 10 billion CFU/gram, about 10 billion CFU/gram to about 20 billion CFU/gram, about 20 billion CFU/gram to about 30 billion CFU/gram, about 30 billion CFU/gram to about 40 billion CFU/gram, or about 40 billion CFU/gram to about 50 billion CFU/gram.

[0059] In another aspect, the ratio of the weight of the first component to the weight of viable probiotic species in the second component is at about 1: 1 to 5:1, about 5: 1 to 10:1, about 10:1 to 15:1, about 15: 1 to 20:1, about 20:1 to 25:1, about 25:1 to 50:1, or about 50: 1 to 100:1. In some embodiments, the ratio is about 6: 1 to 7:1. In some embodiments, the ratio is about 1:1 to 25:1.

[0060] In some embodiments, the second component is absent from the method and the method comprises combining the first component and one or more additional components as described herein.

Additional Components

[0061] In another aspect, the method comprises adding one or more additional components. In some embodiments, the additional component comprises one or more lipids. Such additional components (e.g., lipids) include, but are not limited to, fatty acids, such as omega-3, alpha-linolenic acid, eicosapentaenoic acid or a salt or ester thereof,

docosahexaenoic acid or a salt or ester thereof, omega-6, arachidonic acid or an ester or a salt thereof, linoleic acid or an ester or a salt thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, algal oil, fish oil, chia seed oil, phospholipids such as lecithin, phytoesterols, vitamins, lutein, lycopene, and zeaxanthin. The one or more additional components (e.g., lipids) can be in the form of oils, meats, poultry, oily fish, chocolate, dairy, nuts, or seeds.

[0062] In some embodiments, the additional component comprises one or more type of milk. In some embodiments, the milk is a nutrient-rich liquid food produced by the mammary glands of mammmals. In some embodiments, the milk is a non-mammalian milk manufactured from a plant extract, wheats, seeds or nuts. The one or more type of milk includes, but is not limited to, human milk, cow milk, goat milk, rice milk, oat milk, hemp milk, soy milk, buckwheat milk, amaranth milk, quinoa milk, chia milk, sorghum milk, tapioca milk, millet milk, teff milk, walnut milk, pistachio milk, pecan milk, hazelnut milk, almond milk, cashew milk, flax milk, and coconut milk. The milk can be whole milk, partly skimmed milk, skim milk, buttermilk, raw or unpasteurized milk, calcium fortified milk, filtered milk, lactose-free milk, milk with DHA (i.e., docosahexaenoic acid), omega-3 milk, organic milk, prebiotic fiber milk, evaporated milk, condensed milk, powdered milk, or UHT milk (i.e., Ultra High-Temperature Preseurization). Non-mammalian milk (e.g., plant-based milk, grain-based milk, nut-based milk) can be obtained commercially or prepared by methods known in the art, using one or more steps such as soaking (e.g., in water), draining, grinding, straining, and reconstituting. In some embodiments, the non -mammalian milk is prepared by combining the corresponding grain or nut with water in a 1:4 ratio by volume, soaking for 24-48 hours, draining completely, placing drained grain or nut into a blender with fresh water in a 1:3 ratio by volume, blending completely, straining, and adding water to desired consistency. In some embodiments, the milk is gluten-free. In some embodiments, the additional component comprises kefir. In some embodiments, the kefir is vegan kefir or organic kefir.

[0063] In another aspect, the additional component comprises formula (e.g. , baby or toddler formula). The formula may include, without limitation, one or more of milk formula, dairy-free formula, soy-free formula, lactose-free formula, and vegan formula. In some embodiments, the additional component comprises inulin or walnut.

[0064] In another aspect, the method further comprises a step of adding a

pharmaceutically acceptable carrier, excipient, binder, or diluent. A pharmaceutically- acceptable excipient is a substance that is non-toxic and otherwise biologically suitable for administration to a subject. Such excipients facilitate administration of the compounds described herein and are compatible with the active ingredient. Examples of

pharmaceutically-acceptable excipients include, without limitation, stabilizers, lubricants, surfactants, diluents, anti-oxidants, binders, coloring agents, bulking agents, emulsifiers, or taste-modifying agents. The pharmaceutically acceptable carrier, excipient, binder, or diluent may be added during or after step (i). The pharmaceutically acceptable carrier, excipient, binder, or diluent may be added during or after step (ii).

[0065] In another aspect, the additional component comprises a sugar. Sugars include, without limitation, monosaccharides (e.g., fructose, galactose, glucose, mannose, tagatose, xylose), disaccharides (e.g. , isomaltose, isomaltulose, lactose, maltose, sucrose, trehalose, trehalulose), and sugar alcohols (e.g., erythritol, glycerol, hydrogenated starch hydrolysates, isomalt, lactitol, maltitol, mannitol, sorbitol, xylitol). In some embodiments, the sugar is selected from the group consisting of glucose, fructose, N-acetylglucosamine, galactose, sucrose, mannose, maltose, and lactose. In some embodiments, the sugar is in the form of a syrup.

[0066] In another aspect, the additional component comprises a yogurt starter. In some embodiments, the yogurt starter comprises L. casei, B. longum, L. bulgaricus, S. termophilus, or L. acidophilus. In some embodiments, the yogurt starter comprises S. thermophilus, L. acidophilus, L. casei, L. delbrueckii subsp. bulgaricus, L. rhamnosus, or Bifidobacterium bifidum. In some embodiments, the yogurt starter comprises L. casei, B. longum, L.

bulgaricus, S. thermophilus, and L. acidophilus. In some embodiments, the yogurt start comprises S. thermophilus, L. acidophilus, L.casei, L. delbrueckii subsp. bulgaricus, L.

rhamnosus, and Bifidobacterium bifidum.

[0067] In another aspect, the additional component comprises a bacteriophage, including, without limitation, Myoviridae (e.g., LH01 - Myoviridae, T4D - Myoviridae, and LL12 - Myoviridae), Siphorviridae {e.g., LL5 - Siphorviridae) or Bacteriophage PBC1.

[0068] In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are

galactoligasaccharide and walnut milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and hazelnut milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and cashew milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L.

helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and teff milk milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and quinoa milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and buckwheat milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and amaranth milk. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and L.casei, and the additional component are probiotic yogurt starter and algae oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and fish oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis,

Lactobacillus plantarum, L. salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and intellimune oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and organic cane sugar. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and baby formula.

[0069] In some embodiments, the second component is absent from the method and the method comprises combining the first component and one or more additional components as described herein. In some embodiments, the one or more additional component comprises a prebiotic fiber milk. In some embodiments, the one or more additional components comprises kefir.

Reaction Conditions

[0070] In one aspect, the various components (e.g., the combined first and second components, optionally including any additional components) can be incubated at greater than about 15 °C, greater than about 20 °C, greater than about 25 °C, greater than about 30 °C, greater than about 35 °C, greater than about 40 °C, greater than about 45 °C, greater than about 50 °C, greater than about 55 °C, or greater than about 60 °C. In another aspect, the various components (e.g. , the combined first and second components, optionally including any additional components) can be incubated at lower than about 15 °C, lower than about 20 °C, lower than about 25 °C, lower than about 30 °C, lower than about 35 °C, lower than about 40 °C, lower than about 45 °C, lower than about 50 °C, lower than about 55 °C, or lower than about 60 °C. In some embodiments, the first and second components can be incubated at about 15-20 °C, about 20-25 °C, about 25-30 °C, about 30-35 °C, about 35-40 °C, about 40-45 °C, about 45-50 °C, about 50-55 °C, about 55-60 °C, about 15-25 °C, about 25-35 °C, about 35-45 °C, or about 45-60 °C.

[0071] In some embodiments, the various components (e.g., the combined first and second components, optionally including any additional components) can be incubated at a first temperature and then incubated at a second temperature. The first temperature may be at greater than about 15 °C, greater than about 20 °C, greater than about 25 °C, greater than about 30 °C, greater than about 35 °C, greater than about 40 °C, greater than about 45 °C, greater than about 50 °C, greater than about 55 °C, or greater than about 60 °C. In another aspect, the first temperature may be at lower than about 15 °C, lower than about 20 °C, lower than about 25 °C, lower than about 30 °C, lower than about 35 °C, lower than about 40 °C, lower than about 45 °C, lower than about 50 °C, lower than about 55 °C, or lower than about 60 °C. In some embodiments, the various components (e.g., the combined first and second components, optionally including any additional components) can be incubated at about 15- 20 °C, about 20-25 °C, about 25-30 °C, about 30-35 °C, about 35-40 °C, about 40-45 °C, about 45-50 °C, about 50-55 °C, about 55-60 °C, about 15-25 °C, about 25-35 °C, about 35- 45 °C, or about 45-55 °C. The second temperature may be at greater than about 15 °C, greater than about 20 °C, greater than about 25 °C, greater than about 30 °C, greater than about 35 °C, greater than about 40 °C, greater than about 45 °C, greater than about 50 °C, greater than about 55 °C, or greater than about 60 °C. In another aspect, the second temperature may be at lower than about 15 °C, lower than about 20 °C, lower than about 25 °C, lower than about 30 °C, lower than about 35 °C, lower than about 40 °C, lower than about 45 °C, lower than about 50 °C, lower than about 55 °C, or lower than about 60 °C. In some embodiments, the first and second components can be incubated at about 15-20 °C, about 20-25 °C, about 25-30 °C, about 30-35 °C, about 35-40 °C, about 40-45 °C, about 45- 50 °C, about 50-55 °C, about 55-60 °C, about 15-25 °C, about 25-35 °C, about 35-45 °C, or about 45-60 °C. In some embodiments, the various components (e.g., the combined first and second components, optionally including any additional components) are incubated at the first temperature for a longer period of time than the incubation at the second temperature. In some embodiments, the various components (e.g., the combined first and second components, optionally including any additional components) care incubated at the second temperature for a longer period of time than the incubation at the first temperature.

[0072] In another aspect, the various components (e.g., the combined first and second components, optionally including any additional components) can be incubated for greater than 1 minute, greater than 2 minutes, greater than 4 minutes, greater than 6 minutes, greater than 8 minutes, greater than 10 minutes, greater than 15 minutes, greater than 20 minutes, greater than 25 minutes, greater than 30 minutes, greater than 40 minutes, greater than 50 minutes, greater than 60 minutes, greater than 70 minutes, greater than 80 minutes, greater than 90 minutes, greater than 100 minutes, greater than 120 minutes, greater than 140 minutes, greater than 160 minutes, greater than 180 minutes, greater than 240 minutes, greater than 300 minutes, greater than 360 minutes, greater than 420 minutes, greater than 480 minutes, greater than 540 minutes, greater than 600 minutes, greater than 660 minutes, greater than 720 minutes, or greater than 780 minutes. In some embodiments, the various components (e.g., the combined first and second components, optionally including any additional components) can be incubated for less than 1 minute, less than 2 minutes, less than 4 minutes, less than 6 minutes, less than 8 minutes, less than 10 minutes, less than 15 minutes, less than 20 minutes, less than 25 minutes, less than 30 minutes, less than 40 minutes, less than 50 minutes, less than 60 minutes, less than 70 minutes, less than 80 minutes, less than 90 minutes, less than 100 minutes, less than 120 minutes, less than 140 minutes, less than 160 minutes, less than 180 minutes, less than 200 minutes, less than 250 minutes, less than 300 minutes, less than 400 minutes, less than 500 minutes, less than 600 minutes, less than 700 minutes, less than 800 minutes, less than 900 minutes, or less than

1000 minutes. In some embodiments, the first and second components can be incubated for about 1-5 minutes, about 5-10 minutes, about 10-15 minutes, about 15-20 minutes, about 20- 25 minutes, about 25-30 minutes, about 30-35 minutes, about 35-40 minutes, about 40-45 minutes, about 45-50 minutes, about 50-60 minutes, about 60-80 minutes, about 80-100 minutes, about 100-200 minutes, about 200-300 minutes, about 300-400 minutes, about 400- 500 minutes, about 500-600 minutes, about 600-700 minutes, about 700-800 minutes, about 800-900 minutes, or about 900-1000 minutes. [0073] In some embodiments, and or all of the incubation steps are carried out in a container is suitable for making yogurt. In some embodiments, the container is a yogurt maker or a component thereof. In some embodiments, the yogurt maker is configured for home use or for industrial use. In some embodiments, the container (e.g., yogurt maker) has at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, or at least 20 pots. In some embodiments, the container (e.g., yogurt maker) is configured to apply pressure of about 10- 100 kPa, about 10-30 kPa, about 30-50 kPa, about 50-60 kPa, about 60-70 kPa, about 70-80 kPa or about 80-100 kPa.

[0074] In another aspect, the method further comprises adding one or more lipids (e.g., any lipid described herein). In some embodiments, the lipid is added before step (ii). In some embodiments, the lipid is added during step (ii). In some embodiments, the lipid is combined with the first component prior to combination with the second component. In some embodiments, the lipid is combined with the second component prior to combination with the first component. In some embodiments, the lipid is added after the first and second components are combined.

[0075] In another aspect, the method further comprises adding one or more sugar (e.g., any sugar described herein). In some embodiments, the sugar is added before step (ii) (i.e., before incubating the resulting combination of step (i) at a temperature of at least 15 °C for at least 1 hour or at a temperature of at least 30 °C for at least 8 hours). In some embodiments, the sugar is added during step (ii). In some embodiments, the sugar is combined with the first component prior to combination with the second component. In some embodiments, the sugar is combined with the second component prior to combination with the first component. In some embodiments, the sugar is added after the first and second components are combined with one another.

[0076] In another aspect, the method further comprises adding one or more type of milk. In some embodiments, the milk is added before step (ii). In some embodiments, the milk is added during step (ii). In some embodiments, the milk is combined with the first component prior to combination with the second component. In some embodiments, the milk is combined with the second component prior to combination with the first component. In some embodiments, the milk is added after the first and second components are combined with one another. In some embodiments, the first and second components are added to the milk. In some embodiments, the milk is incubated before being added to the combination of the first and second components. In some embodiments, the milk is incubated at greater than 30 °C, greater than 40 °C, greater than 50 °C, greater than 60 °C, greater than 70 °C, greater than 80 °C, greater than 90 °C, or greater than 100 °C. In some embodiments, the milk is incubated for at least 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, or 30 minutes. In some embodiments, after incubation, the milk is cooled down before being added to the first and/or second components. In some embodiments, the milk is cooled down to lower than 70 °C, lower than 60 °C, lower than 50 °C, lower than 40 °C, lower than 30 °C, or lower than 20 °C before being added to the first and/or second components.

[0077] In another aspect, the method further comprises adding formula (e.g. , baby formula). In some embodiments, the formula is added before step (ii). In some

embodiments, the formula is added during step (ii). In some embodiments, the formula is combined with the first component prior to combination with the second component. In some embodiments, the formula is combined with the second component prior to

combination with the first component. In some embodiments, the formula is added after the first and second components are combined with one another. In some embodiments, the first and second components are added to the formula. In some embodiments, the formula is incubated before being added to the combination of the first and second components. In some embodiments, the formula is incubated at greater than 30 °C, greater than 40 °C, greater than 50 °C, greater than 60 °C, greater than 70 °C, greater than 80 °C, greater than 90 °C, or greater than 100 °C. In some embodiments, the formula is incubated for at least 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, or 30 minutes. In some embodiments, after incubation, the formula is cooled down before being added to the first and/or second components. In some embodiments, the formula is cooled down to lower than 70 °C, lower than 60 °C, lower than 50 °C, lower than 40 °C, lower than 30 °C, or lower than 20 °C before being added to the first and/or second components.

[0078] In some embodiments, the first, second, and optional additional components are combined in a sterilized container. In some embodiments, the container comprises glass, metal, plastic, or a mixture of any of the foregoing. In some embodiments, the container is sterilized by boiling in water for at least 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, or 30 minutes. In some embodiments, the container is sterilized by steam sterilization, wherein saturated steam is injected into a pressure chamber at a temperature in the range of 100-200 °C for a period of time sufficient to provide sterilization. In some embodiments, the container is sterilized by dry heat. In some embodiments, the container is suitable for making yogurt. In some embodiments, the sterilized container is a yogurt maker or a component thereof. In some embodiments, the yogurt maker is configured for home use or for industrial use. In some embodiments, the container (e.g., yogurt maker) has at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, or at least 20 pots. In some embodiments, the container (e.g., yogurt maker) is configured to apply pressure of about 10-100 kPa, about 10- 30 kPa, about 30-50 kPa, about 50-60 kPa, about 60-70 kPa, about 70-80 kPa or about 80-100 kPa.

[0079] In some embodiments, the container is sterilized in boiling water for about 5-30 minutes, followed by adding milk and incubating the milk until it reaches about 50-70°C. Then the milk is cooled down to lower than 50 °C before mixing in the first and second components. In some embodiments, the container is sterilized in dry heat for about 10-45 minutes, followed by adding milk and incubating the milk until it reaches about 50-70°C. Then the milk is cooled down to lower than 50 °C before mixing in algae oil or fish oil to form a starter culture. Then the first and second components are added to the culture.

[0080] In another aspect, the method described herein produces urolithin A at greater than about 0.005%, or greater than about 0.010%, or greater than about 0.015%, or greater than about 0.020%, or greater than about 0.025%, or greater than about 0.030%, or greater than about 0.035%, or greater than about 0.040%, or greater than about 0.045%, or greater than about 0.050%, or greater than about 0.055%, or greater than about 0.060%, or greater than about 0.065%, or greater than about 0.070%, or greater than about 0.075%, or greater than 0.080%, or greater than 0.090%, or greater than 0.10% by weight of the total product (e.g., of the total yogurt product). In some embodiments, the method described herein produces urolithin A at less than 0.010%, or less than about 0.020%, or less than about 0.030%, or less than about 0.040%, or less than about 0.050%, or less than about 0.060%, or less than about 0.070%, or less than about 0.080%, or less than about 0.090%, or less than about 0.10%, or less than about 0.20%, or less than about 0.30%, or less than about 0.40%, or less than about 0.50%, or less than about 1.0%, or less than 2.0% by weight of the total product (e.g., of the total yogurt product). [0081] In another aspect, the method described herein produces urolithin B at greater than about 0.005%, or greater than about 0.010%, or greater than about 0.015%, or greater than about 0.020%, or greater than about 0.025%, or greater than about 0.030%, or greater than about 0.035%, or greater than about 0.040%, or greater than about 0.045%, or greater than about 0.050%, or greater than about 0.055%, or greater than about 0.060%, or greater than about 0.065%, or greater than about 0.070%, or greater than about 0.075%, or greater than 0.080%, or greater than 0.090%, or greater than 0.10% by weight of the of the total product (e.g., of the total yogurt product). In some embodiments, the method described herein produces urolithin B at less than 0.010%, or less than about 0.020%, or less than about 0.030%, or less than about 0.040%, or less than about 0.050%, or less than about 0.060%, or less than about 0.070%, or less than about 0.080%, or less than about 0.090%, or less than about 0.10%, or less than about 0.20%, or less than about 0.30%, or less than about 0.40%, or less than about 0.50%, or less than about 1.0%, or less than 2.0% by weight of the total product (e.g., of the total yogurt product).

[0082] In another aspect, the method described herein produces a combination of urolithin A and urolithin B at greater than about 0.005%, or greater than about 0.015%, or greater than about 0.025%, or greater than about 0.035%, or greater than about 0.045%, or greater than about 0.055%, or greater than about 0.065%, or greater than about 0.075%, or greater than about 0.085%, or greater than about 0.095%, or greater than about 0.10%, or greater than about 0.15%, or greater than about 0.20%, or greater than about 0.25%, or greater than about 0.30%, or greater than 0.40%, or greater than 0.50% by weight of the total product (e.g., of the total yogurt product). In some embodiments, the method described herein produces a combination of urolithin A and urolithin B at less than 5.0%, or less than about 2.5%, or less than about 1.0%, or less than about 0.9%, or less than about 0.80%, or less than about 0.70%, or less than about 0.60%, or less than about 0.50%, or less than about 0.40%, or less than about 0.30%, or less than about 0.20%, or less than about 0.10%, or less than about 0.080%, or less than about 0.060%, or less than about 0.040%, or less than 0.020%, or less than 0.010% by weight of the total product (e.g., of the total yogurt product).

[0083] In some embodiments, the composition may be subject to downstream purification to produce UA or UB. Downstream purification can be accomplished by any processes known in the art, including but not limited to, filtration, centrifugation, extraction, crystallization, chromatography and distillation. In some embodiments, the composition or the purified compounds are further concentrated. In some embodiments, the concentrated compounds have a concentration at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, lO-fold, 20-fold, 30-fold, 50-fold, 75-fold, or lOO-fold higher than the concentration prior to the concentration step. In some embodiments, the compositions or the purified compounds may be subject to downstream formulation and/or packaging. In some embodiments, the compositions or the purified compounds are formulated in the form of a food product or a dietary supplement.

[0084] In another aspect, the purity of the urolithin A or urolithin B after downstream purification is greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by total weight of the purified product.

[0085] In some embodiments, the additional components are heated to about 40-45 °C, about 50-55 °C, about 60-65 °C, about 70-75 °C, about 80-85 °C, about 90-95 °C, or about 100-110 °C prior to adding to the reaction mixture. In some embodiments, the additional components are cooled down to about 55-60 °C, about 50-55 °C, about 45-50 °C, about 40- 45 °C, about 35-40 °C, about 30-35 °C, about 25-30 °C, or about 20-65 °C prior to adding to the reaction mixture. In some embodiments, the additional components are selected from the group consisting of cow milk, goat milk, cashew milk, oat milk, hemp milk, and coconut milk. In some embodiments, the milk is heated to about 80-85 °C then cooled down to about 40-50 °C prior to adding to the reaction mixture.

[0086] In some embodiments, a compound of formula (I) is present in the resulting mixture of step (ii) (e.g., after incubating the combination of step (i) at a temperature of at least 30 °C for at least 8 hours). In other embodiments, the resulting mixture of step (ii) contains one or more intermediate compounds that are converted to a compound of formula (I) in the digestive tract (e.g. , gastrointestinal tract) following ingestion or other

administration of the mixture to an individual. The conversion of an intermediate resulting from the method provided herein to a compound of formula (I) may be the result of metabolism of the one or more intermediate compounds by microbiota in the digestive tract (e.g., gastrointestinal tract) of the individual. In some embodiments, the microbiota in the digestive tract (e.g., gastrointestinal tract) of the individual include one or more probiotic species described herein.

[0087] In another aspect, the disclosure relates to a method for preparing a compound of formula (I):

wherein Ri, R2, R3, R4, Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof; comprising: (i) combining (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a prebiotic component, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

[0088] In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours. In some embodiments, the prebiotic component comprises prebiotic fiber. In some embodiments, the prebiotic fiber can be obtained from one or more of bananas, onions, garlic, Jerusalem artichoke, apples, chicory root, oatmeal, asparagus, dandelion greens, barley and beans. In some embodiments, the prebiotic component comprises kefir.

[0089] Any first components and any reaction conditions described herein can be used in the method described herein.

[0090] In some embodiments, the first component is ellatic acid and the second component is kefir milk (e.g., kefir plain lowfat milk, probiotic mango coconut milk kefir, pure kefir, or ginger turmeric kefir).

Compositions [0091] In some aspects, provided herein is a composition comprising:

(a) a first component selected from the group consisting of pomegranate extract, pomegranate juice, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a second component comprising one or more probiotic species.

[0092] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g. ,

Lactobacillus acidophilus La- 14 and Lactobacillus acidophilus LA85), Lactobacillus plantarum {e.g., Lactobacillus plantarum Lp90), Lactobacillus rhamnosus {e.g. ,

Lactobacillus rhamnosus Lr-32 and Lactobacillus rhamnosus LRa05), Lactobacillus reuteri {e.g., Lactobacillus reuteri LR08), Lactobacillus casei {e.g., Lactobacillus casei LC89), Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius {e.g. ^

Lactobacillus salivarius LS97), Lactobacillus fermentum {e.g., Lactobacillus fermentum LF15), Lactobacillus crispatus {e.g. , Lactobacillus crispatus LCr86), Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis {e.g.,

Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g. , Bifidobacterium longum Bl-05, B. longum BL21 and B. longum infantis BI45), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815), Ellagibacter isourolithinifaciens {e.g., Ellagibacter isourolithinifaciens DSM 104140), Enterorhabdus musicola DSM 19490 {e.g., Enterorhabdus musicola DSM 19490), Enterorhabdus caecimuris {e.g., Enterorhabdus caecimuris DSM 21839), Adlercreutzia equolifaciens {e.g., Adlercreutzia equolifaciens DSM 19450), Asaccharobacter celatus {e.g., Asaccharobacter celatus DSM 18785), Parvibacter caecicola {e.g. , Parvibacter caecicola DSM 22242), Gordonibacter urolithinfaciens (CEB AS 1/15P), Gordonibacter pamelaeae {e.g., Gordonibacter pamelaeae 7-lO-l-b) and

Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0093] In some embodiments, the second component comprises a mixture of

Akkermansia muciniphila, Lactobacillus acidophilus (e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc- 37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus . In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02,

Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Akkermansia muciniphila, Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus delbrueckii {e.g., Lactobacillus delbrueckii subsp. bulgaricus), Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus casei. In some embodiments, the second component comprises a mixture of Lactobacillus casei, Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus, and Lactobacillus acidophilus. In some embodiments, the second component comprises a mixture of Streptococcus

thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus rhamnosus, Bifidobacterium pseudocatenulatum and Bifidobacterium bifidum. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus La- 14, Bifidobacterium lactis Bl-04, Lactobacillus paracasei Lpc-37, Lactobacillus rhamnosus Lr-32, Bifidobacterium bifidum/lactis Bb-02, Bifidobacterium pseudocatenulatum INIA P815 and Bifidobacterium longum Bl-05. In some embodiments, the second component comprises one or more of Ellagibacter isourolithinifaciens {e.g., Ellagibacter isourolithinifaciens DSM 104140), Enterorhabdus musicola DSM 19490 {e.g. , Enterorhabdus musicola DSM 19490),

Enterorhabdus caecimuris {e.g., Enterorhabdus caecimuris DSM 21839), Adlercreutzia equolifaciens {e.g., Adlercreutzia equolifaciens DSM 19450), Asaccharobacter celatus {e.g., Asaccharobacter celatus DSM 18785), Parvibacter caecicola {e.g., Parvibacter caecicola DSM 22242), Gordonibacter urolithinfaciens (CEB AS 1/15P) and Gordonibacter pamelaeae {e.g., Gordonibacter pamelaeae 7-lO-l-b).

[0094] In one aspect, the composition comprises the first component at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by total weight of the composition. In another aspect, the composition comprises the first component at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by total weight of the composition.

[0095] In another aspect, the first component is present at about 1-1000 mg, 1000-2000 mg, 2000-3000 mg, 3000-4000 mg, 4000-5000 mg, 5000-6000 mg, 6000-7000 mg, 7000- 8000 mg, 8000-9000 mg, 9000-10000 mg, 1-200 mg, 200-400 mg, 400-600 mg, 600-800 mg, 800-1000 mg, 1000-1200 mg, 1200-1400 mg, 1400-1600 mg, 1600-1800 mg, 1800-2000 mg, 2000-2200 mg, 2200-2400 mg, 2400-2600 mg, 2600-2800 mg, 2800-3000 mg, 3200-3400 mg, 3400-3600 mg, 3600-3800 mg, 3800-4000 mg, 4000-4200 mg, 4200-4400 mg, 4400- 4600 mg, 4600-4800 mg, 4800-5000 mg, 5000-5200 mg, 5200-5400 mg, 5400-5600 mg, 5600-5800 mg, 5800-6000 mg, 6000-6200 mg, 6200-6400 mg, 6400-6600 mg, 6600-6800 mg, 6800-7000 mg, 7000-7200 mg, 7200-7400 mg, 7400-7600 mg, 7600-7800 mg, 7800- 8000 mg, 8000-8200 mg, 8200-8400 mg, 8400-8600 mg, 8600-8800 mg, 8800-9000 mg, 9000-9200 mg, 9200-9400 mg, 9400-9600 mg, 9600-9800 mg, or 9800-10000 mg. In some embodiments, first component is present at about 5-10 g, 10-20 g, 20-30 g, 30-40 g, 40-50 g, 50-75 g or 75-100 g.

[0096] In another aspect, the composition comprises the second component at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by total weight of the composition. In another aspect, the composition comprises the second component at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by total weight of the composition.

[0097] In another aspect, the second component is at about 1 CFU to about 100 CFU, about 100 CFU to about 1,000 CFU, about 1,000 CFU to about 10,000 CFU, about 10,000 CFU to about 100,000 CFU, about 100,000 CFU to about 1 million CFU, about 1 million CFU to about 10 million CFU, about 10 million CFU to about 100 million CFU, about 100 million CFU to about 200 million CFU, about 200 million to about 400 million CFU, about 400 million to about 600 million CFU, about 600 million to about 800 million CFU, about 800 million to about 1000 million CFU, about 1000 million to about 2000 million CFU, about 2000 million to about 3000 million CFU, about 3000 million to about 4000 million CFU, about 4000 million to about 5000 million CFU, about 5000 million to about 6000 million CFU, about 6000 million to about 7000 million CFU, about 7000 million to about 8000 million CFU, about 8000 million to about 9000 million CFU, about 9000 million to about 1 billion CFU, about 1 billion to about 10 billion CFU, about 10 billion to about 50 billion CFU, about 50 billion to about 100 billion CFU, about 100 billion to about 200 billion CFU, about 200 billion to about 300 billion CFU, about 300 billion to about 400 billion CFU, about 400 billion to about 500 billion CFU, about 500 billion to about 600 billion CFU, about 600 billion to about 700 billion CFU, about 700 billion to about 800 billion CFU, about 800 billion to about 900 billion CFU, about 900 billion to about 1000 billion CFU, about 1000 billion to about 1500 billion CFU, about 1500 billion to about 2000 billion CFU, about 2000 billion to about 2500 billion CFU, about 2500 billion to about 3000 billion CFU, about 3000 billion to about 3500 billion CFU, about 3500 billion to about 4000 billion CFU, about 4000 billion to about 4500 billion CFU, or about 4500 billion to about 5000 billion CFU.

[0098] In another aspect, the composition comprises a combined amount of first and second components at about 1-1000 mg, 1000-2000 mg, 2000-3000 mg, 3000-4000 mg, 4000-5000 mg, 5000-6000 mg, 6000-7000 mg, 7000-8000 mg, 8000-9000 mg, 9000-10000 mg, 1-200 mg, 200-400 mg, 400-600 mg, 600-800 mg, 800-1000 mg, 1000-1200 mg, 1200- 1400 mg, 1400-1600 mg, 1600-1800 mg, 1800-2000 mg, 2000-2200 mg, 2200-2400 mg, 2400-2600 mg, 2600-2800 mg, 2800-3000 mg, 3000-3200 mg, 3200-3400 mg, 3400-3600 mg, 3600-3800 mg, 3800-4000 mg, 4000-4200 mg, 4200-4400 mg, 4400-4600 mg, 4600- 4800 mg, 4800-5000 mg, 5000-5200 mg, 5200-5400 mg, 5400-5600 mg, 5600-5800 mg, 5800-6000 mg, 6000-6200 mg, 6200-6400 mg, 6400-6600 mg, 6600-6800 mg, 6800-7000 mg, 7000-7200 mg, 7200-7400 mg, 7400-7600 mg, 7600-7800 mg, 7800-8000 mg, 8000- 8200 mg, 8200-8400 mg, 8400-8600 mg, 8600-8800 mg, 8800-9000 mg, 9000-9200 mg, 9200-9400 mg, 9400-9600 mg, 9600-9800 mg, 9800-10000 mg, 1-5 g, 5-10 g, 10-20 g, 20-30 g, 30-40 g, 40-50 g, 50-70 g, 70-100 g, 100-245 g, 245-300 g, 300-400 g, 400-500 g, 500-600 g, 600-700 g, 700-800 g, 800-900 g, or 900-1000 g. .

[0099] In some embodiments, the composition comprises a combined amount of first and second components at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by total weight of the composition. In some embodiments, the composition comprises a combined amount of first and second components at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by total weight of the composition.

[0100] In another aspect, the first component comprises a mixture of pomegranate extract, an ellagitannin or a salt thereof, or ellagic acid or a salt thereof. In some

embodiments, the first component comprises one or more ellagitannins and ellagic acid. In some embodiments, the first component comprises one or more ellagitannins. In some embodiments, the first component comprises one or more ellagitannins and pomegranate extract. In some embodiments, the first component comprises one or more ellagitannins and pomegranate extract. In some embodiments, the first component comprises ellagic acid and pomegranate extract. In some embodiments, the first component comprises one or more urolithins. In some embodiments, the first component comprises one or more ellagitannins, ellagic acid, and pomegranate extract. In some embodiments, the first component comprises punicalagin and ellagic acid. In some embodiments, the first component comprises punicalagin and pomegranate extract. In some embodiments, the first component comprises punicalagin, pomegranate extract, and ellagic acid.

[0101] In some embodiments, the first component comprises salts of one or more ellagitannins and ellagic acid. In some embodiments, the first component comprises salts of one or more ellagitannins. In some embodiments, the first component comprises salts of one or more ellagitannins and pomegranate extract. In some embodiments, the first component comprises salts of ellagic acid and pomegranate extract. In some embodiments, the first component comprises salts of one or more ellagitannins, ellagic acid, and pomegranate extract. In some embodiments, the first component comprises salts of punicalagin and ellagic acid. In some embodiments, the first component comprises salts of punicalagin and one or pomegranate extract. In some embodiments, the first component comprises salts of punicalagin, ellagic acid, and pomegranate extract. In some embodiments, pomegranate juice may be used in addition to or as an alternative to pomegranate extract.

[0102] In one aspect, the second component comprises a mixture of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the second component comprises Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the second component comprises Akkermansia muciniphila and Bifidobacterium infantis. In some embodiments, the second component comprises Akkermansia muciniphila and Lactobacillus plantarum. In some embodiments, the second component is Akkermansia muciniphila and Lactobacillus rhamnosus. In some embodiments, the second component comprises Akkermansia muciniphila and Lactobacillus reuteri. In some embodiments, the second component comprises Akkermansia muciniphila and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus acidophilus and Bifidobacterium infantis. In some embodiments, the second component comprises Lactobacillus acidophilus and Lactobacillus plantarum. In some embodiments, the second component comprises Lactobacillus acidophilus and Lactobacillus rhamnosus. In some embodiments, the second component comprises Lactobacillus acidophilus and Lactobacillus reuteri. In some embodiments, the second component comprises Lactobacillus acidophilus and Bifidobacterium breve. In some embodiments, the second component comprises Bifidobacterium infantis and Lactobacillus plantarum. In some embodiments, the second component comprises Bifidobacterium infantis and Lactobacillus rhamnosus. In some embodiments, the second component comprises Bifidobacterium infantis and Lactobacillus reuteri. In some embodiments, the second component comprises Bifidobacterium infantis and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus plantarum and Lactobacillus rhamnosus. In some embodiments, the second component comprises Lactobacillus plantarum and Lactobacillus reuteri. In some embodiments, the second component comprises Lactobacillus plantarum and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus reuteri and Bifidobacterium breve. In some embodiments, the second component is Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium pseudocatenulatum and Lactobacillus reuteri. In some embodiments, the second component comprises Bifidobacterium infantis, Bifidobacterium breve and Lactobacillus acidophilus. In some embodiments, the second component comprises Akkermansia muciniphila,

Bifidobacterium infantis, Bifidobacterium breve and Lactobacillus acidophilus. In some embodiments, the second component comprises Akkermansia muciniphila, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the second component comprises Bifidobacterium infantis, Lactobacillus plantarum,

Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve. In some embodiments, the second component comprises Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium infantis. In some embodiments, the second component comprises Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0103] In another aspect, the one or more probiotic species in the second component are present at greater than about 1 CFU/gram, greater than about 5 CFU/gram, greater than about 10 CFU/gram, greater than about 50 CFU/gram, greater than about 100 CFU/gram, greater than about 500 CFU/gram, greater than about 1,000 CFU/gram, greater than about 5,000 CFU/gram, greater than about 10,000 CFU/gram, greater than about 50,000 CFU/gram, greater than about 100,000 CFU/gram, greater than about 500,000 CFU/gram, greater than about 1 million CFU/gram, greater than about 50 million CFU/gram, greater than about 100 million CFU/gram, greater than about 150 million CFU/gram, greater than about 200 million CFU/gram, greater than about 250 million CFU/gram, greater than about 300 million

CFU/gram, greater than about 350 million CFU/gram, greater than about 400 million

CFU/gram, greater than about 450 million CFU/gram, greater than about 500 million

CFU/gram, greater than about 550 million CFU/gram, greater than about 600 million

CFU/gram, greater than about 650 million CFU/gram, greater than about 700 million

CFU/gram, greater than about 750 million CFU/gram, greater than about 800 million

CFU/gram, greater than about 850 million CFU/gram, greater than about 900 million

CFU/gram, greater than about 950 million CFU/gram, greater than about 1 billion CFU/gram, greater than about 2 billion CFU/gram, greater than about 3 billion CFU/gram, greater than about 4 billion CFU/gram, greater than about 5 billion CFU/gram, greater than about 6 billion CFU/gram, greater than about 7 billion CFU/gram, greater than about 8 billion CFU/gram, greater than about 9 billion CFU/gram, greater than about 10 billion CFU/gram, greater than about 20 billion CFU/gram, greater than about 30 billion CFU/gram, greater than about 40 billion CFU/gram, or greater than about 50 billion CFU/gram at the time of manufacture. In some embodiments, the one or more probiotic species in the second component are present at about 1 CFU/gram to about 100 CFU/gram, about 100 CFU/gram to about 1,000 CFU/gram, about 1,000 CFU/gram to about 10,000 CFU/gram, about 10,000 CFU/gram to about 100,000 CFU/gram, about 100,000 CFU/gram to about 1 million CFU/gram, about 1 million

CFU/gram to about 10 million CFU/gram, about 10 million CFU/gram to about 20 million CFU/gram, about 20 million CFU/gram to about 30 million CFU/gram, about 30 million CFU/gram to about 40 million CFU/gram, about 40 million CFU/gram to about 50 million CFU/gram, about 50 million CFU/gram to about 60 million CFU/gram, about 60 million CFU/gram to about 70 million CFU/gram, about 70 million CFU/gram to about 80 million CFU/gram, about 80 million CFU/gram to about 90 million CFU/gram, about 90 million CFU/gram to about 100 million CFU/gram, about 100 million CFU/gram to about 200 million CFU/gram, about 200 million CFU/gram to about 300 million CFU/gram, about 300 million CFU/gram to about 400 million CFU/gram, about 400 million CFU/gram to about 500 million CFU/gram, about 500 million CFU/gram to about 600 million CFU/gram, about 600 million CFU/gram to about 700 million CFU/gram, about 700 million CFU/gram to about 800 million CFU/gram, about 800 million CFU/gram to about 900 million CFU/gram, about 900 million CFU/gram to about 1 billion CFU/gram, about 1 billion CFU/gram to about 2 billion CFU/gram, about 2 billion CFU/gram to about 3 billion CFU/gram, about 3 billion CFU/gram to about 4 billion CFU/gram, about 4 billion CFU/gram to about 5 billion CFU/gram, about 5 billion CFU/gram to about 6 billion CFU/gram, about 6 billion

CFU/gram to about 7 billion CFU/gram, about 7 billion CFU/gram to about 8 billion CFU/gram, about 8 billion CFU/gram to about 9 billion CFU/gram, about 9 billion

CFU/gram to about 10 billion CFU/gram, about 10 billion CFU/gram to about 20 billion CFU/gram, about 20 billion CFU/gram to about 30 billion CFU/gram, about 30 billion CFU/gram to about 40 billion CFU/gram, or about 40 billion CFU/gram to about 50 billion CFU/gram.

[0104] In another aspect, the ratio of the weight of the first component to the weight of viable probiotic species in the second component is at about 1: 1 to 5:1, about 5: 1 to 10:1, about 10:1 to 15:1, about 15: 1 to 20:1, about 20:1 to 25:1, about 25:1 to 50:1, or about 50: 1 to 100:1. In some embodiments, the ratio is about 6: 1 to 7:1. In some embodiments, the ratio is about 1:1 to 25:1.

[0105] In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are

galactoligasaccharide and walnut milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and hazelnut milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and cashew milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L.

helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and teff milk milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and quinoa milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and buckwheat milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and amaranth milk. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and L.casei, and the additional component are probiotic yogurt starter and algae oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and fish oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis,

Lactobacillus plantarum, L. salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and intellimune oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and organic cane sugar. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and baby formula. [0106] In some embodiments, the second component is absent from the composition and the composition comprises the first component and one or more additional components as described herein.

[0107] In another aspect, the composition may further comprise one or more additional components such as lipids. The additional components (e.g., lipids) include, but are not limited to, fatty acids, such as omega-3, alpha-linolenic acid, eicosapentaenoic acid or a salt or ester thereof, docosahexaenoic acid or a salt or ester thereof, omega-6, arachidonic acid or an ester or a salt thereof, linoleic acid or an ester or a salt thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, algal oil, fish oil, chia seed oil, phospholipids, such as lecithin, phytoesterols, vitamins, lutein, lycopene, and zeaxanthin.

The one or more additional components (e.g., lipids) can be in the form of oils, meats, poultry, oily fish, chocolate, dairy, nuts, or seeds. In some embodiments, the composition further comprises fish oil, algal oil, chia seed oil, eicosapentaenoic acid, docosahexaenoic acid, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, or a mixture thereof. In some embodiments, the composition further comprises fish oil and algal oil. In some

embodiments, the composition further comprises chia seed oil and ethyl eicosapentaenoic acid. In some embodiments, the composition further comprises fish oil and omega-3 acid ethyl ester. In some embodiments, the composition further comprises algal oil and eicosapentaenoic acid. In some embodiments, the composition further comprises algal oil and docosahexaenoic acid. In some embodiments, the composition further comprises algal oil and ethyl eicosapentaenoic acid. In some embodiments, the composition further comprises algal oil and omega-3 acid ethyl ester. In some embodiments, the composition further comprises eicosapentaenoic acid and docosahexaenoic acid. In some embodiments, the composition further comprises eicosapentaenoic acid and ethyl eicosapentaenoic acid. In some embodiments, the composition further comprises eicosapentaenoic acid and omega-3 acid ethyl ester. In some embodiments, the composition further comprises docosahexaenoic acid and ethyl eicosapentaenoic acid. In some embodiments, the composition further comprises docosahexaenoic acid and omega-3 acid ethyl ester. In some embodiments, the composition further comprises ethyl eicosapentaenoic acid and omega-3 acid ethyl ester. In some embodiments, the composition further comprises fish oil, algal oil, and ethyl eicosapentaenoic acid. In some embodiments, the composition further comprises fish oil, algal oil, and omega-3 acid ethyl ester. In some embodiments, the composition further comprises eicosapentaenoic acid, docosahexaenoic acid, and ethyl eicosapentaenoic acid. In some embodiments, the composition further comprises docosahexaenoic acid, ethyl eicosapentaenoic acid, and omega-3 acid ethyl ester. In some embodiments, the composition further comprises fish oil, eicosapentaenoic acid, and docosahexaenoic acid. In some embodiments, the composition further comprises chia seed oil, algal oil, eicosapentaenoic acid, docosahexaenoic acid, ethyl eicosapentaenoic acid, and omega-3 acid ethyl ester.

[0108] In some embodiments, the composition further comprises salts of fish oil, eicosapentaenoic acid, or docosahexaenoic acid. In some embodiments, the salt is a pharmaceutically acceptable salt. In some embodiments, pharmaceutically acceptable salts include, without limitation, acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, oxalic acid, propionic acid, succinic acid, maleic acid, tartaric acid and the like. These salts may be derived from inorganic or organic acids. Non-limiting examples of pharmaceutically acceptable salts include, without limitation, sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen- phosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-l,4-dioates, hexyne-l,6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, methylsulfonates, propylsulfonates, besylates, xylenesulfonates, naphthalene- 1- sulfonates, naphthalene-2-sulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, g-hydroxybutyrates, glycolates, tartrates, and mandelates. In some embodiments, pharmaceutically acceptable salts are formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base. Salts derived from pharmaceutically acceptable organic non-toxic bases include, without limitation, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2- diethylaminoethanol, tromethamine, trimethamine, dicyclohexylamine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, N- ethylglucamine, N- methylglucamine, theobromine, purines, piperazine, piperidine, N- ethylpiperidine, polyamine resins, amino acids such as lysine, arginine, histidine, and the like. Examples of pharmaceutically acceptable base addition salts include, without limitation, those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. In some embodiments, the organic non-toxic bases are I, -amino acids, such as L-lysine and L- arginine, tromethamine, N-ethylglucamine and N-methylgluc amine. Acceptable inorganic bases include, without limitation, aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, and the like. Lists of other suitable pharmaceutically acceptable salts are found in Remington's Pharmaceutical Sciences, l7th Edition, Mack Publishing Company, Easton, Pa., 1985. In some embodiments, the composition further comprises salts of fish oil. In some embodiments, the composition further comprises salts of eicosapentaenoic acid. In some embodiments, the composition further comprises salts of docosahexaenoic acid.

[0109] In some embodiments, the additional component comprises one or more type of milk. In some embodiments, the milk is a nutrient-rich liquid food produced by the mammary glands of mammmals. In some embodiments, the milk is a non-mammalian milk manufactured from a plant extract, wheats, seeds or nuts. The one or more type of milk includes, but is not limited to, human milk, cow milk, goat milk, rice milk, oat milk, hemp milk, soy milk, buckwheat milk, amaranth milk, quinoa milk, chia milk, sorghum milk, tapioca milk, millet milk, teff milk, walnut milk, pistachio milk, pecan milk, hazelnut milk, almond milk, cashew milk, flax milk, and coconut milk. The milk can be whole milk, partly skimmed milk, skim milk, buttermilk, raw or unpasteurized milk, calcium fortified milk, filtered milk, lactose-free milk, milk with DHA (/. <? ., docosahexaenoic acid), omega-3 milk, organic milk, prebiotic fiber milk, evaporated milk, condensed milk, powdered milk, or UHT milk (/. <? ., Ultra High-Temperature Preseurization). In some embodiments, the milk is gluten- free. In some embodiments, the additional component comprises kefir. In some

embodiments, the kefir is vegan kefir or organic kefir.

[0110] In another aspect, the composition further comprises formula (e.g., baby or toddler formula). The formula includes, without limitation, milk formula, dairy-free formula, soy- free formula, lactose-free formula, and vegan formula. In some embodiments, the additional component comprises inulin or walnut.

[0111] In another aspect, the composition further comprises a yogurt starter. In some embodiments, the yogurt starter comprises L. casei, B. longum, L. bulgaricus, S.

thermophilus, or L. acidophilus. In some embodiments, the yogurt start comprises S. thermophilus, L acidophilus, L casei, L delbrueckii subsp. bulgaricus, L rhamnosus, or Bifidobacterium bifidum. In some embodiments, the yogurt starter comprises L casei, B. longum, L. bulgaricus, S. thermophilus, and L. acidophilus. In some embodiments, the yogurt start comprises S. thermophilus, L. acidophilus, Lcasei, L. delbrueckii subsp.

bulgaricus, L. rhamnosus, and Bifidobacterium bifidum.

[0112] In another aspect, the composition further comprises a sugar. In some embodiments, the sugar is selected from the group consisting of glucose, fructose, N- acetylglucos amine, galactose, sucrose, mannose, maltose, and lactose. In some embodiments, the sugar is in the form of a syrup.

[0113] In some embodiments, the composition further comprises a bacteriophage, including, without limitation, Myoviridae (e.g., LH01 - Myoviridae, T4D - Myoviridae , and LL12 - Myoviridae), Siphorviridae (e.g., LL5 - Siphorviridae) or Bacteriophage PBC1.

[0114] In another aspect, the composition further comprises urolithin A (UA) and/or urolithin B (UB).

Urolithin A Urolithin B

[0115] In some embodiments, the second component is absent from the composition and the composition comprises the first component and the one or more additional components as described herein. In some embodiments, the one or more additional components comprise a prebiotic fiber milk. In some embodiments, the one or more additional components comprises kefir.

[0116] In some embodiments, the composition comprises pomegranate extract and Akkermansia muciniphila. In some embodiments, the composition comprises pomegranate extract and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract and Bifidobacterium infantis. In some embodiments, the composition comprises pomegranate extract and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract and Bifidobacterium pseudocatenulatum. In some embodiments, the composition comprises pomegranate extract and Lactobacillus rhamnosus. In some embodiments, the composition comprises pomegranate extract and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract,

Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0117] In some embodiments, the composition comprises one or more ellagitannins and Akkermansia muciniphila. In some embodiments, the composition comprises one or more ellagitannins and Lactobacillus acidophilus. In some embodiments, the composition comprises one or more ellagitannins and Bifidobacterium pseudocatenulatum. In some embodiments, the composition comprises one or more ellagitannins and Bifidobacterium infantis. In some embodiments, the composition comprises one or more ellagitannins and Lactobacillus plantarum. In some embodiments, the composition comprises one or more ellagitannins and Lactobacillus rhamnosus. In some embodiments, the composition comprises one or more ellagitannins and Lactobacillus reuteri. In some embodiments, the composition comprises one or more ellagitannins and Bifidobacterium breve. In some embodiments, the composition comprises one or more ellagitannins, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises one or more ellagitannins, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises one or more ellagitannins, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises one or more ellagitannins, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises one or more ellagi tannins, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises one or more ellagitannins, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises one or more ellagitannins, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises one or more ellagitannins, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0118] In some embodiments, the composition comprises ellagic acid and Akkermansia muciniphila. In some embodiments, the composition comprises ellagic acid and

Lactobacillus acidophilus. In some embodiments, the composition comprises ellagic acid and Bifidobacterium infantis. In some embodiments, the composition comprises ellagic acid and Lactobacillus plantarum. In some embodiments, the composition comprises ellagic acid and Lactobacillus rhamnosus. In some embodiments, the composition comprises ellagic acid and Lactobacillus reuteri. In some embodiments, the composition comprises ellagic acid and Bifidobacterium breve. In some embodiments, the composition comprises ellagic acid and Bifidobacterium pseudocatenulatum. In some embodiments, the composition comprises ellagic acid, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises ellagic acid, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises ellagic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises ellagic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises ellagic acid, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises ellagic acid, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises ellagic acid, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises ellagic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. [0119] In some embodiments, the composition comprises one or more ellagitannins, ellagic acid and Akkermansia muciniphila. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid and Lactobacillus acidophilus. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid and Bifidobacterium infantis. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid and Bifidobacterium pseudocatenulatum. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid and Lactobacillus plantarum. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid and

Lactobacillus rhamnosus. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid and Lactobacillus reuteri. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid and Bifidobacterium breve. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid,

Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid,

Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid,

Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid,

Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid,

Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises one or more ellagitannins, ellagic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0120] In some embodiments, the composition comprises pomegranate extract, ellagic acid and Akkermansia muciniphila. In some embodiments, the composition comprises pomegranate extract, ellagic acid and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract, ellagic acid and Bifidobacterium infantis. In some embodiments, the composition comprises pomegranate extract, ellagic acid and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract, ellagic acid and Bifidobacterium pseudocatenulatum. In some embodiments, the composition comprises pomegranate extract, ellagic acid and Lactobacillus rhamnosus. In some embodiments, the composition comprises pomegranate extract, ellagic acid and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, ellagic acid and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, ellagic acid, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract, ellagic acid, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract, ellagic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, ellagic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, ellagic acid, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, ellagic acid, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, ellagic acid, Bifidobacterium

pseudocatenulatum, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, ellagic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0121] In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, Lactobacillus plantarum, Lactobacillus rhamnosus, and

Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, Bifidobacterium inf antis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, Akkermansia muciniphila, Lactobacillus acidophilus,

Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0122] In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, UA, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, UB, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0123] In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Lactobacillus rhamnosus, Lactobacillus reuteri,

Bifidobacterium pseudocatenulatum and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0124] In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, chia seed oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0125] In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve.

[0126] In some embodiments, the composition comprises salts of one or more ellagitannins, ellagic acid, fish oil, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the composition comprises salts of one or more ellagitannins, ellagic acid, fish oil, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the composition comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the composition comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the composition comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the composition comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0127] In some aspects, also provided herein is a composition comprising:

(a) a first component selected from the group consisting of pomegranate extract, pomegranate juice, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a prebiotic component.

[0128] In some embodiments, the prebiotic component comprises prebiotic fiber. In some embodiments, the prebiotic fiber can be obtained from one or more of bananas, onions, garlic, Jerusalem artichoke, apples, chicory root, oatmeal, asparagus, dandelion greens, barley and beans. In some embodiments, the prebiotic component comprises kefir. In some embodiments, the first component is ellatic acid and the second component is kefir milk (e.g., kefir plain lowfat milk, probiotic mango coconut milk kefir, pure kefir, or ginger turmeric kefir).

[0129] In one aspect, provided herein is a urolithin (e.g., UA or UB) produced by any of the methods described herein. In some embodiments, the urolithin is part of a yogurt composition.

[0130] The typical concentration of urolithins circulating in the plasma is in the range of about 0.2-20 mM. Espin et al. (2013) Evid. based Complement Alternat. Med. 2013, 270418. In another aspect, the composition provided herein comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject. In some embodiments, the composition comprises an amount of the first component and an amount of the second component effective to treat or prevent a disease or condition that can benefit from elevated urolithin above natural levels within the subject. In some embodiments, the composition comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to treat or prevent a mitochondrial disease or condition. In some embodiments, the mitochondrial disease or condition is selected from the group consisting of aging, diabetes, obesity and neurodegenerative disease. In some embodiments, the composition comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to enhance or maintain muscle growth or performance. In some embodiments, the composition comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to extend lifespan. In some embodiments, the elevated urolithin level is at least about 2-fold, about 3-fold, about 4- fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about lO-fold, about l5-fold, about 20-fold, about 30-fold, about 40-fold, about 50-fold, about 75-fold, or about lOO-fold higher than the natural levels. In some embodiments, the increase in urolithin levels in an individual subject may be evaluated by comparison to the subject’s urolithin levels as determined (e.g., measured) prior to administration of the composition to the subject. In other embodiments, the increase in urolithin levels in an individual subject may be evaluated by comparison with the normal (e.g., average) urolithin levels of a comparable population of subjects.

Pharmaceutical Compositions

[0131] The present disclosure also relates to pharmaceutical compositions comprising the composition and a pharmaceutically acceptable carrier, excipient, binder, or diluent.

[0132] The pharmaceutical compositions may comprise any of the compositions described herein. In some embodiments, the pharmaceutical composition comprises the compound produced by the method described herein. In some embodiments, the

pharmaceutical composition comprises any combination of the first and the second components described herein.

[0133] In some embodiments, the pharmaceutical compositions comprise one or more pharmaceutically acceptable excipients. A pharmaceutically-acceptable excipient is a substance that is non- toxic and otherwise biologically suitable for administration to a subject. Such excipients facilitate administration of the compounds described herein and are compatible with the active ingredient. Examples of pharmaceutically-acceptable excipients include, without limitation, stabilizers, lubricants, surfactants, diluents, anti-oxidants, binders, coloring agents, bulking agents, emulsifiers, or taste-modifying agents. In some

embodiments, pharmaceutical compositions according to the embodiments are sterile compositions. Pharmaceutical compositions may be prepared using compounding techniques known or that become available to those skilled in the art. Sterile compositions are also contemplated by the embodiments, including compositions that are in accord with national and local regulations governing such compositions.

[0134] The pharmaceutical compositions and compounds described herein may be formulated as solutions, emulsions, suspensions, dispersions, or inclusion complexes such as cyclodextrins in suitable pharmaceutical solvents or carriers, or as pills, tablets, bars, lozenges, suppositories, sachets, dragees, granules, powders, powders for reconstitution, or capsules along with solid carriers according to conventional methods known in the art for preparation of various dosage forms. Pharmaceutical compositions provided herein may be administered by a suitable route of delivery, such as oral and parenteral. In some embodiments, the compositions are formulated for intravenous or oral administration·

[0135] For oral administration, the pharmaceutical composition may be provided in a solid form, such as a tablet or capsule, or as a solution, emulsion, or suspension. To prepare the oral compositions, the pharmaceutical composition may be formulated to yield a dosage of a combined first and second components, e.g., from about 1 to about 100 mg/kg daily, or from about 100 mg to about 1 g/kg daily, or from about 1 g to about 20 g/kg daily. In some embodiments, the dosage of the first component is from about 1 to about 50 mg/kg daily, from 50 mg to about 1 g/kg daily, or from about 1 g to about 10 g/kg daily. In some embodiments, the dosage of the second component is from about 1 to about 50 mg/kg daily, from 50 mg to about 1 g/kg daily, or from about 1 g to about 10 g/kg daily. Oral tablets may include the active ingredient(s) mixed with compatible pharmaceutically acceptable excipients such as diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservative agents. Suitable inert fillers include sodium and calcium carbonate, sodium and calcium phosphate, lactose, starch, sugar, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol, and the like.

Exemplary liquid oral excipients include ethanol, glycerol, water, and the like. Starch, polyvinyl-pyrrolidone (PVP), sodium starch glycolate, microcrystalline cellulose, and alginic acid are exemplary disintegrating agents. Binding agents may include starch and gelatin.

The lubricating agent, if present, may be magnesium stearate, stearic acid, or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate to delay absorption in the digestive tract (e.g., gastrointestinal tract), or may be coated with an enteric coating.

[0136] Capsules for oral administration include hard and soft gelatin capsules. To prepare hard gelatin capsules, active ingredient(s) may be mixed with a solid, semi-solid, or liquid diluent. Soft gelatin capsules may be prepared by mixing the active ingredient with water, an oil such as peanut oil or olive oil, liquid paraffin, a mixture of mono and di glycerides of short chain fatty acids, polyethylene glycol 400, or propylene glycol.

[0137] Liquids for oral administration may be in the form of suspensions, solutions, emulsions, or syrups, or may be lyophilized or presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid compositions may optionally contain: pharmaceutically-acceptable excipients such as suspending agents (for example, sorbitol, methyl cellulose, sodium alginate, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel and the like); non-aqueous vehicles, e.g., oil (for example, almond oil or fractionated coconut oil), propylene glycol, ethyl alcohol, or water; preservatives (for example, methyl or propyl p-hydroxybenzoate or sorbic acid); wetting agents such as lecithin; and, if desired, flavoring or coloring agents.

[0138] The first and second components may be formulated together or individually. In some embodiments, the first component is formulated as a food product or dietary supplement. In some embodiments, the second component is formulated as a food product.

In some embodiments, the second component is formulated as a yogurt.

Food Product and Dietary Supplement

[0139] The present disclosure also relates to compositions in the form of a food product or a dietary supplement.

[0140] A food product comprises a substance that can be used or prepared for use as food. A food product may be in a solid or a liquid (e.g., beverage) form. A food product may contain fruits, plants, vegetables, nuts, or seeds, or juice, extracts, jam, concentrate, wheat, or alcohol of any of the foregoing. A food product may also contain milk, yogurt, meat, fish, or processed products thereof. A food product may comprise flowers, leaves or bark of a plant. A food product may be a product prepared from a natural food. A food product may be a medical food, a functional food, a food additive or a nutritional food. A medical food comprises foods that are specially formulated and intended for dietary management of a disease or condition that has distinctive nutritional needs that cannot be met by normal diet alone. Medical foods can be for oral ingestion or tube feeding. A functional food comprises foods that have a potentially positive effect on health beyond basic nutrition. A food additive comprises any substance added to food, where its intended use results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food. The addition of food additives may occur during production, processing, treatment, packaging, transportation or storage of food. A nutritional food comprises foods that provide a high amount of nutrients. In some embodiments, the nutritional foods also comprise few calories.

[0141] A dietary supplement comprises a manufactured product intended to supplement the diet. A dietary supplement can be synthetic or natural. A dietary supplement can comprise one component or more than one component in combination. In some

embodiments, the dietary supplement is an addition to the human or animal diet, which is not a natural or conventional food. A dietary supplement may comprise vitamins, amino acids, probiotics, minerals, fiber, fatty acids, pigments, polyphenols, lipids, or proteins. In some embodiments, the dietary supplement may be formulated as a pharmaceutical composition as discussed herein. In some embodiments, the dietary supplement is intended to be taken by mouth as a pill, capsule, tablet, or liquid. In some embodiments, the dietary supplement comprises a label as being a dietary supplement. In some embodiments, the dietary supplement comprises non-dietary ingredients such as fillers, artificial colors, sweeteners, flavors, or binders.

[0142] In some embodiments, the food product or dietary supplement comprises an effective amount of the composition for the treatment or prevention of a condition that can benefit from administration of urolithin compounds. In some embodiments, the condition is a mitochondrial disease, such as aging, diabetes, obesity, or a neurodegenerative disease. In some embodiments, the condition is muscle performance deficiency, muscle growth deficiency, or metabolic deficiency.

[0143] The typical concentration of urolithins circulating in the plasma is in the range of about 0.2-20 mM. Espin et al. (2013) Evid. based Complement Alternat. Med. 2013, 270418. In some embodiments, the food product or dietary supplement provided herein comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject. In some embodiments, the food product or dietary supplement comprises an amount of the first component and an amount of the second component effective to treat or prevent a disease or condition that can benefit from elevated urolithin above natural levels within the subject. In some embodiments, the food product or dietary supplement comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to treat or prevent a mitochondrial disease or condition. In some embodiments, the mitochondrial disease or condition is selected from the group consisting of aging, diabetes, obesity and neurodegenerative disease. In some embodiments, the food product or dietary supplement comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to enhance or maintain muscle growth or performance. In some embodiments, the food product or dietary supplement comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to extend lifespan. In some embodiments, the elevated urolithin level is at least about 2-fold, about 3 -fold, about 4-fold, about 5 -fold, about 6-fold, about 7-fold, about 8-fold, about 9- fold, about 10-fold, about 15 -fold, about 20-fold, about 30-fold, about 40-fold, about 50-fold, about 75-fold, or about lOO-fold higher than the natural level.

Kits

[0144] Provided herein are kits comprising:

(a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a second component comprising one or more probiotic species.

[0145] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g.,

Lactobacillus acidophilus La- 14 and Lactobacillus acidophilus LA85), Lactobacillus plantarum {e.g., Lactobacillus plantarum Lp90), Lactobacillus rhamnosus {e.g.,

Lactobacillus rhamnosus Lr-32 and Lactobacillus rhamnosus LRa05), Lactobacillus reuteri {e.g., Lactobacillus reuteri LR08), Lactobacillus casei {e.g., Lactobacillus casei LC89), Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius {e.g. ^

Lactobacillus salivarius LS97), Lactobacillus fermentum {e.g., Lactobacillus fermentum LF15), Lactobacillus crispatus {e.g. , Lactobacillus crispatus LCr86), Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis {e.g.,

Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g. , Bifidobacterium longum Bl-05, B. longum BL21 and B. longum infantis BI45), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815), Ellagibacter isourolithinifaciens {e.g., Ellagibacter isourolithinifaciens DSM 104140), Enterorhabdus musicola DSM 19490 ( e.g ., Enterorhabdus musicola DSM 19490), Enterorhabdus caecimuris (e.g., Enterorhabdus caecimuris DSM 21839), Adlercreutzia equolifaciens (e.g., Adlercreutzia equolifaciens DSM 19450), Asaccharobacter celatus (e.g., Asaccharobacter celatus DSM 18785), Parvibacter caecicola (e.g. , Parvibacter caecicola DSM 22242), Gordonibacter urolithinfaciens (CEB AS 1/15P), Gordonibacter pamelaeae (e.g., Gordonibacter pamelaeae 7-lO-l-b) and

Streptococcus thermophilus . In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0146] In one aspect, the kits may contain instructions for use in the treatment or prevention of a condition in a subject in need thereof. In some embodiments, the condition that can benefit from administration of urolithin compounds. In some embodiments, the condition is mitochondrial disease, such as aging, diabetes, obesity, and neurodegenerative diseases. In some embodiments, the condition is muscle performance deficiency, muscle growth deficiency, or metabolic deficiency. A kit may additionally contain any materials or equipment that may be used in the administration of the compound or composition, such as vials, syringes, or IV bags. A kit may also contain sterile packaging.

[0147] In another aspect, the kit may contain any composition described herein. In another aspect, the kit may contain any pharmaceutical composition described herein.

[0148] In some embodiments, the kit comprises urolithin A (UA) and/or urolithin B (UB) (e.g., prepared by any method described herein). In some embodiments, the kit comprises ellagic acid and one or more ellagitannins. In some embodiments, the kit comprises ellagic acid and one or more urolithins. In some embodiments, the kit comprises pomegranate extract and one or more urolithins. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, and one or more urolithins. In some embodiments, the kit comprises pomegranate extract, ellagic acid, and one or more urolithins. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, and one or more urolithins. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, and UA. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, and UB. [0149] In some embodiments, the kit comprises a mixture of Akkermansia muciniphila, Lactobacillus acidophilus (e.g. , Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp.

bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), and Streptococcus thermophilus . In some embodiments, the kit comprises a mixture of Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La-l4), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium lactis {e.g. , Bifidobacterium lactis Bl-04),

Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium

pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the kit comprises a mixture of Akkermansia muciniphila, Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La-l4), Lactobacillus plantarum, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the kit comprises a mixture of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus casei. In some embodiments, the kit comprises a mixture of Lactobacillus casei, Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus, Bifidobacterium pseudocatenulatum and Lactobacillus acidophilus. In some embodiments, the kit comprises a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp.

bulgaricus), Lactobacillus rhamnosus, and Bifidobacterium bifidum. In some embodiments, the kit comprises a mixture of Lactobacillus acidophilus La- 14, Bifidobacterium lactis Bl-04, Lactobacillus paracasei Lpc-37, Lactobacillus rhamnosus Lr-32, Bifidobacterium bifidum/lactis Bb-02, Bifidobacterium pseudocatenulatum INIA P815 and Bifidobacterium longum Bl-05. In some embodiments, the second component comprises one or more of Ellagibacter isourolithinifaciens ( e.g ., Ellagibacter isourolithinifaciens DSM 104140), Enterorhabdus musicola DSM 19490 {e.g., Enterorhabdus musicola DSM 19490),

Enterorhabdus caecimuris {e.g., Enterorhabdus caecimuris DSM 21839), Adlercreutzia equolifaciens {e.g., Adlercreutzia equolifaciens DSM 19450), Asaccharobacter celatus {e.g., Asaccharobacter celatus DSM 18785), Parvibacter caecicola {e.g., Parvibacter caecicola DSM 22242), Gordonibacter urolithinfaciens (CEB AS 1/15P) and Gordonibacter pamelaeae {e.g., Gordonibacter pamelaeae 7-lO-l-b).

[0150] In some embodiments, the kit comprises Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises

Bifidobacterium infantis, Bifidobacterium breve and Lactobacillus acidophilus. In some embodiments, the kit comprises Akkermansia muciniphila, Bifidobacterium infantis, Bifidobacterium breve and Lactobacillus acidophilus. In some embodiments, the kit comprises Akkermansia muciniphila, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve. In some embodiments, the kit comprises Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium infantis. In some embodiments, the kit comprises Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0151] In some embodiments, the kit comprises pomegranate extract and Akkermansia muciniphila. In some embodiments, the kit comprises pomegranate extract and Lactobacillus acidophilus. In some embodiments, the kit comprises pomegranate extract and

Bifidobacterium infantis. In some embodiments, the kit comprises pomegranate extract and Lactobacillus plantarum. In some embodiments, the kit comprises pomegranate extract and Lactobacillus rhamnosus. In some embodiments, the kit comprises pomegranate extract and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract and Bifidobacterium pseudocatenulatum. In some embodiments, the kit comprises pomegranate extract, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the kit comprises pomegranate extract, Bifidobacterium infantis, and Lactobacillus plantarum.

In some embodiments, the kit comprises pomegranate extract, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, Lactobacillus acidophilus,

Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve.

[0152] In some embodiments, the kit comprises one or more ellagitannins and

Akkermansia muciniphila. In some embodiments, the kit comprises one or more ellagitannins and Lactobacillus acidophilus. In some embodiments, the kit comprises one or more ellagitannins and Bifidobacterium infantis. In some embodiments, the kit comprises one or more ellagitannins and Lactobacillus plantarum. In some embodiments, the kit comprises one or more ellagitannins and Lactobacillus rhamnosus. In some embodiments, the kit comprises one or more ellagitannins and Lactobacillus reuteri. In some embodiments, the kit comprises one or more ellagitannins and Bifidobacterium breve. In some embodiments, the kit comprises one or more ellagitannins and Bifidobacterium pseudocatenulatum. In some embodiments, the kit comprises one or more ellagitannins, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the kit comprises one or more

ellagitannins, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises one or more ellagitannins, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises one or more ellagitannins, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises one or more ellagitannins, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises one or more ellagitannins, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises one or more ellagitannins, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises one or more ellagitannins, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, pomegranate juice may be used in addition to or as an alternative to pomegranate extract.

[0153] In some embodiments, the kit comprises ellagic acid and Akkermansia muciniphila. In some embodiments, the kit comprises ellagic acid and Lactobacillus acidophilus. In some embodiments, the kit comprises ellagic acid and Bifidobacterium infantis. In some embodiments, the kit comprises ellagic acid and Lactobacillus plantarum.

In some embodiments, the kit comprises ellagic acid and Lactobacillus rhamnosus. In some embodiments, the kit comprises ellagic acid and Lactobacillus reuteri. In some

embodiments, the kit comprises ellagic acid and Bifidobacterium pseudocatenulatum. In some embodiments, the kit comprises ellagic acid and Bifidobacterium breve. In some embodiments, the kit comprises ellagic acid, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the kit comprises ellagic acid, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises ellagic acid,

Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises ellagic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises ellagic acid, Lactobacillus acidophilus,

Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises ellagic acid, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises ellagic acid, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve. In some embodiments, the kit comprises ellagic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0154] In some embodiments, the kit comprises one or more ellagitannins, ellagic acid and Akkermansia muciniphila. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid and Lactobacillus acidophilus. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid and Bifidobacterium pseudocatenulatum. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid and

Bifidobacterium infantis. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid and Lactobacillus plantarum. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid and Lactobacillus rhamnosus. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid and Lactobacillus reuteri. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid and Bifidobacterium breve. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid,

Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises one or more ellagitannins, ellagic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve.

[0155] In some embodiments, the kit comprises pomegranate extract, ellagic acid and Akkermansia muciniphila. In some embodiments, the kit comprises pomegranate extract, ellagic acid and Lactobacillus acidophilus. In some embodiments, the kit comprises pomegranate extract, ellagic acid and Bifidobacterium infantis. In some embodiments, the kit comprises pomegranate extract, ellagic acid and Bifidobacterium pseudocatenulatum. In some embodiments, the kit comprises pomegranate extract, ellagic acid and Lactobacillus plantarum. In some embodiments, the kit comprises pomegranate extract, ellagic acid and Lactobacillus rhamnosus. In some embodiments, the kit comprises pomegranate extract, ellagic acid and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, ellagic acid and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, ellagic acid, Akkermansia muciniphila and Lactobacillus acidophilus.

In some embodiments, the kit comprises pomegranate extract, ellagic acid, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises pomegranate extract, ellagic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, ellagic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, ellagic acid, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, ellagic acid, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, ellagic acid, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, ellagic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve.

[0156] In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve.

[0157] The kit described herein may further comprise urolithin A (UA) or/and urolithin B (UB) (e.g., prepared by any method described herein). In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Lactobacillus plantarum,

Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins,

Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, one or more urolithins, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, UA, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus,

Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, UB, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0158] In another aspect, the kit may further comprise fish oil or a salt thereof, algal oil, eicosapentaenoic acid or a salt or ester thereof, docosahexaenoic acid or a salt or ester thereof, ethyl eicosapentaenoic or an ester acid, omega-3 acid ethyl ester, or a mixture thereof. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Akkermansia muciniphila and Lactobacillus acidophilus.

In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, chia seed oil, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil,

Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri.

In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0159] In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Akkermansia muciniphila and Lactobacillus acidophilus. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Lactobacillus rhamnosus, Lactobacillus reuteri, and

Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Bifidobacterium infantis, Lactobacillus plantarum,

Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0160] In another aspect, the kit may further comprise one or more milk. In some embodiments, the milk is a nutrient-rich liquid food produced by the mammary glands of mammmals. In some embodiments, the milk is a non-mammalian milk manufactured from a plant extract, wheats, seeds or nuts. The one or more type of milk includes, but is not limited to, human milk, cow milk, goat milk, rice milk, oat milk, hemp milk, soy milk, buckwheat milk, amaranth milk, quinoa milk, chia milk, sorghum milk, tapioca milk, millet milk, teff milk, walnut milk, pistachio milk, pecan milk, hazelnut milk, almond milk, cashew milk, flax milk, and coconut milk. The milk can be whole milk, partly skimmed milk, skim milk, buttermilk, raw or unpasteurized milk, calcium fortified milk, filtered milk, lactose-free milk, milk with DHA (/. <? ., docosahexaenoic acid), omega-3 milk, organic milk, prebiotic fiber milk, evaporated milk, condensed milk, powdered milk, or UHT milk (/. <? ., Ultra High- Temperature Preseurization). In some embodiments, the milk is gluten-free. In some embodiments, the additional component comprises kefir. In some embodiments, the kefir is vegan kefir or organic kefir.

[0161] In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Akkermansia muciniphila and Lactobacillus acidophilus. In some

embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, chia seed oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises pomegranate extract, one or more ellagitannins, ellagic acid, fish oil, ethyl eicosapentaenoic acid, omega-3 acid ethyl ester, one or more milk, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve.

[0162] In some embodiments, the kit comprises salts of one or more ellagitannins, ellagic acid, fish oil, Akkermansia muciniphila and Lactobacillus acidophilus. In some

embodiments, the kit comprises salts of one or more ellagitannins, ellagic acid, fish oil, Bifidobacterium infantis, and Lactobacillus plantarum. In some embodiments, the kit comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid,

docosahexaenoic acid, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises salts of one or more ellagitannins, ellagic acid,

eicosapentaenoic acid, docosahexaenoic acid, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Lactobacillus acidophilus, Bifidobacterium infantis, and Bifidobacterium breve. In some embodiments, the kit comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri. In some embodiments, the kit comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. In some embodiments, the kit comprises salts of one or more ellagitannins, ellagic acid, eicosapentaenoic acid, docosahexaenoic acid, Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium breve. [0163] In another aspect, the kit further comprises formula (e.g., baby or toddler formula). The formula may include, without limitation, milk formula, dairy-free formula, soy-free formula, lactose- free formula, and vegan formula.

[0164] In another aspect, the kit further comprises a sugar. In some embodiments, the sugar is selected from the group consisting of glucose, fructose, N-acetylglucosamine, galactose, sucrose, mannose, maltose, and lactose. In some embodiments, the sugar is in the form of a syrup.

[0165] In some embodiments, the kit further comprises a bacteriophage, including, without limitation, Myoviridae (e.g., LH01 - Myoviridae, T4D - Myoviridae, and LL12 - Myoviridae ), Siphorviridae (e.g., LL5 - Siphorviridae) or Bacteriophage PBC1.

[0166] In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are

galactoligasaccharide and walnut milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and hazelnut milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and cashew milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L.

helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and teff milk milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and quinoa milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and buckwheat milk. In some embodiments, the first component is ellagic acid, the second component is 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus and L. rhamnosus, and the additional components are galactoligasaccharide and amaranth milk. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and L.casei, and the additional component are probiotic yogurt starter and algae oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and fish oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis,

Lactobacillus plantarum, L. salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and intellimune oil. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and organic cane sugar. In some embodiments, the first component is ellagic acid, the second component is Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L salivarius, B. bifidum, B. longum, L. rhamnosus, and Lcasei, and the additional components are probiotic yogurt starter and baby formula.

[0167] In another aspect, the kit comprises the first component at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by weight of the combined first and second components in the kit. In another aspect, the kit comprises the first component at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by weight of the combined first and second components in the kit.

[0168] In another aspect, the first component is present in the kit at about 1-1000 mg, 1000-2000 mg, 2000-3000 mg, 3000-4000 mg, 4000-5000 mg, 5000-6000 mg, 6000-7000 mg, 7000-8000 mg, 8000-9000 mg, 9000-10000 mg, 1-200 mg, 200-400 mg, 400-600 mg, 600-800 mg, 800-1000 mg, 1000-1200 mg, 1200-1400 mg, 1400-1600 mg, 1600-1800 mg, 1800-2000 mg, 2000-2200 mg, 2200-2400 mg, 2400-2600 mg, 2600-2800 mg, 2800-3000 mg, 3200-3400 mg, 3400-3600 mg, 3600-3800 mg, 3800-4000 mg, 4000-4200 mg, 4200- 4400 mg, 4400-4600 mg, 4600-4800 mg, 4800-5000 mg, 5000-5200 mg, 5200-5400 mg, 5400-5600 mg, 5600-5800 mg, 5800-6000 mg, 6000-6200 mg, 6200-6400 mg, 6400-6600 mg, 6600-6800 mg, 6800-7000 mg, 7000-7200 mg, 7200-7400 mg, 7400-7600 mg, 7600- 7800 mg, 7800-8000 mg, 8000-8200 mg, 8200-8400 mg, 8400-8600 mg, 8600-8800 mg, 8800-9000 mg, 9000-9200 mg, 9200-9400 mg, 9400-9600 mg, 9600-9800 mg, 9800-10000 mg, 10-20 g,. 20-30 g, 30-40 g, 40-50 g, 50-75 g, 75-100 g, 100-150 g, or 150-200 g.

[0169] In another aspect, the kit comprises the second component at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by weight of the combined first and second components in the kit. In another aspect, the kit comprises the second component at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by weight of the combined first and second components in the kit.

[0170] In another aspect, the second component is present in the kit at 1 CFU to about 100 CFU, about 100 CFU to about 1,000 CFU, about 1,000 CFU to about 10,000 CFU, about 10,000 CFU to about 100,000 CFU, about 100,000 CFU to about 1 million CFU, about 1 million CFU to about 10 million CFU, about 10 million CFU to about 100 million CFU, about 100 million CFU to about 200 million CFU, about 200 million to about 400 million CFU, about 400 million to about 600 million CFU, about 600 million to about 800 million CFU, about 800 million to about 1000 million CFU, about 1000 million to about 2000 million CFU, about 2000 million to about 3000 million CFU, about 3000 million to about 4000 million CFU, about 4000 million to about 5000 million CFU, about 5000 million to about 6000 million CFU, about 6000 million to about 7000 million CFU, about 7000 million to about 8000 million CFU, about 8000 million to about 9000 million CFU, about 9000 million to about 1 billion CFU, about 1 billion to about 10 billion CFU, about 10 billion to about 50 billion CFU, about 50 billion to about 100 billion CFU, about 100 billion to about 200 billion CFU, about 200 billion to about 300 billion CFU, about 300 billion to about 400 billion CFU, about 400 billion to about 500 billion CFU, about 500 billion to about 600 billion CFU, about 600 billion to about 700 billion CFU, about 700 billion to about 800 billion CFU, about 800 billion to about 900 billion CFU, about 900 billion to about 1000 billion CFU, about 1000 billion to about 1500 billion CFU, about 1500 billion to about 2000 billion CFU, about 2000 billion to about 2500 billion CFU, about 2500 billion to about 3000 billion CFU, about 3000 billion to about 3500 billion CFU, about 3500 billion to about 4000 billion CFU, about 4000 billion to about 4500 billion CFU, or about 4500 billion to about 5000 billion CFU.

[0171] In another aspect, the kit comprises a combined amount of first and second components at about 1-1000 mg, 1000-2000 mg, 2000-3000 mg, 3000-4000 mg, 4000-5000 mg, 5000-6000 mg, 6000-7000 mg, 7000-8000 mg, 8000-9000 mg, 9000-10000 mg, 1-200 mg, 200-400 mg, 400-600 mg, 600-800 mg, 800-1000 mg, 1000-1200 mg, 1200-1400 mg, 1400-1600 mg, 1600-1800 mg, 1800-2000 mg, 2000-2200 mg, 2200-2400 mg, 2400-2600 mg, 2600-2800 mg, 2800-3000 mg, 3000-3200 mg, 3200-3400 mg, 3400-3600 mg, 3600- 3800 mg, 3800-4000 mg, 4000-4200 mg, 4200-4400 mg, 4400-4600 mg, 4600-4800 mg, 4800-5000 mg, 5000-5200 mg, 5200-5400 mg, 5400-5600 mg, 5600-5800 mg, 5800-6000 mg, 6000-6200 mg, 6200-6400 mg, 6400-6600 mg, 6600-6800 mg, 6800-7000 mg, 7000- 7200 mg, 7200-7400 mg, 7400-7600 mg, 7600-7800 mg, 7800-8000 mg, 8000-8200 mg, 8200-8400 mg, 8400-8600 mg, 8600-8800 mg, 8800-9000 mg, 9000-9200 mg, 9200-9400 mg, 9400-9600 mg, 9600-9800 mg, 9800-10000 mg, 10-20 g,. 20-30 g, 30-40 g, 40-50 g, 50- 75 g, 75-100 g, 100-150 g, or 150-200 g.

[0172] In some embodiments, the kit comprises a combined amount of first and second components at greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by weight of combined first, second, and additional components in the kit. In some embodiments, the kit comprises a combined amount of first and second components at less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by weight of combined first, second, and additional components in the kit.

[0173] In another aspect, the ratio of the weight of the first component to the weight of viable probiotic species in the second component is at about 1: 1 to 5:1, about 5: 1 to 10:1, about 10:1 to 15:1, about 15: 1 to 20:1, about 20:1 to 25:1, about 25:1 to 50:1, or about 50: 1 to 100:1. In some embodiments, the ratio is about 6: 1 to 7:1. In some embodiments, the ratio is about 1:1 to 25:1.

[0174] In another aspect, the kit comprises a pharmaceutical composition comprising the first component and a pharmaceutically acceptable carrier, excipient, binder or diluent. In another aspect, the kit comprises a pharmaceutical composition comprising the second component and a pharmaceutically acceptable carrier, excipient, binder or diluent.

[0175] The first or second component described herein may be formulated as solutions, emulsions, suspensions, dispersions, or inclusion complexes such as cyclodextrins in suitable pharmaceutical solvents or carriers, or as pills, tablets, lozenges, suppositories, sachets, dragees, granules, powders, powders for reconstitution, or capsules along with solid carriers according to conventional methods known in the art for preparation of various dosage forms. The components provided herein may be administered by a suitable route of delivery, such as oral or parenteral. In some embodiments, the components are formulated for oral

administration.

[0176] The first and second components can be formulated separately in two

formulations or together in one formulation. In some embodiments, the first and second components are formulated together as solutions, emulsions, suspensions, dispersions, or inclusion complexes such as cyclodextrins in suitable pharmaceutical solvents or carriers, or as pills, tablets, bars, lozenges, suppositories, sachets, dragees, granules, powders, powders for reconstitution, or capsules along with solid carriers according to conventional methods known in the art for preparation of various dosage forms. In some embodiments, the first and second components are formulated separately. In some embodiments, the first and second components are formulated in different forms. In some embodiments, the first component is formulated as a liquid, and the second component is formulated as a solid. In some embodiments, the first component is formulated as a solid, and the second component is formulated as a liquid. In some embodiments, the first component is formulated as a solution or suspension, and the second component is formulated as a pill or tablet. In some embodiments, the first component is formulated as a pill or tablet, and the second component is formulated as a solution or suspension. The first and second components of the kit can be formulated, together or separately, in any manner and with any excipients or other ingredients described herein.

[0177] In some embodiments, the first and second components are formulated for simultaneous administration. In some embodiments, the first and second components are formulated for sequential administration· In some embodiments, the first and second components are formulated for administration via different routes. In some embodiments, the first and second components are administered in the same route. In some embodiments, the administration of the first component and the administration of the second component are 1- 30 mins, 30-60 mins, 60-120 mins, 120-180 mins, 180-240 mins, 240-300 mins, or 300-600 mins apart. In some embodiments, the first component is administered before (e.g., 30 minutes , 1, 2, 3, 4, 5, 6, 12, or 24 hours, or 1, 2, or 3 days before) the second component. In some embodiments, the second component is administered before (e.g., 30 minutes , 1, 2, 3,

4, 5, 6, 12, or 24 hours, or 1, 2, or 3 days before) the first component.

[0178] In another aspect, the first or second component may be in the form of a food product or a dietary supplement. In some embodiments, the first or second component is administered in the form of natural food, including fruits, vegetables, plants, meat, milk, nuts, or seeds. In some embodiments, the first or second component is administered in the form of a processed food product, including juice, extract, concentrate, jam, or alcohol. In some embodiments, the first component is administered as pomegranate juice, concentrate, or fruit.

[0179] In other aspects, the kits may be used for any of the methods described herein, including, for example, to treat or prevent a mitochondrial disease, to enhance metabolic rate or to extend lifespan.

[0180] The typical concentration of urolithins circulating in the plasma is in the range of about 0.2-20 mM. Espin et al. (2013) Evid. based Complement Alternat. Med. 2013, 270418. In some embodiments, the kit provided herein comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject. In some embodiments, the kit comprises an amount of the first component and an amount of the second component effective to treat or prevent a disease or condition that can benefit from elevated urolithin above natural levels within the subject. In some embodiments, the kit comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to treat or prevent a mitochondrial disease or condition. In some embodiments, the

mitochondrial disease or condition is selected from the group consisting of aging, diabetes, obesity and neurodegenerative disease. In some embodiments, the kit comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to enhance or maintain muscle growth or performance. In some embodiments, the kit comprises an amount of the first component and an amount of the second component effective to elevate the urolithin above natural levels within the subject to extend lifespan. In some embodiments, the elevated urolithin level is at least about 2-fold, about 3 -fold, about 4-fold, about 5 -fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about lO-fold, about l5-fold, about 20-fold, about 30-fold, about 40-fold, about 50-fold, about 75-fold, or about lOO-fold higher than the natural level.

[0181] In another aspect, kits for treating a subject who suffers from or is susceptible to the conditions described herein are provided, comprising a first container comprising a dosage amount of a composition as disclosed herein, and instructions for use. The container may be any of those known in the art and appropriate for storage and delivery of the formulation. In certain embodiments, the kit further comprises a second container comprising a pharmaceutically acceptable carrier, diluent, adjuvant, etc. for preparation of the formulation to be administered to the subject.

[0182] The kits may optionally include appropriate instructions for preparation and administration of the formulation, side effects of the formulation, and any other relevant information. The instructions may be in any suitable format, including, but not limited to, printed matter, videotape, computer readable disk, optical disc or directions to internet-based instructions.

[0183] The kits may contain sufficient dosages of the compositions described herein (including pharmaceutical compositions thereof) to provide effective treatment for a subject for an extended period, such as 1-3 days, 1-5 days, a week, 2 weeks, 3, weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months or more.

[0184] The kits may also include multiple doses of the composition and instructions for use and may be packaged in quantities sufficient for storage and use in pharmacies, for example, hospital pharmacies and compounding pharmacies. In certain embodiments the kits may include a dosage amount of at least one composition as disclosed herein.

[0185] The kits may include the composition as described herein packaged in either a unit dosage form or in a multi-use form. The kits may also include multiple units of the unit dose form.

[0186] The kits may also comprise a means for the delivery of the composition thereof.

[0187] In some embodiments, the second component is absent from the kit, and the kit comprises the first component and one or more additional components as described herein.

In some embodiments, the one or more additional component comprises a prebiotic fiber milk. In some embodiments, the one or more additional component comprises kefir.

[0188] Also provided herein are kits comprising:

(a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a prebiotic component.

[0189] In some embodiments, the prebiotic component comprises prebiotic fiber. In some embodiments, the prebiotic fiber can be obtained from one or more of bananas, onions, garlic, Jerusalem artichoke, apples, chicory root, oatmeal, asparagus, dandelion greens, barley and beans. In some embodiments, the prebiotic component comprises kefir. In some embodiments, the first component is ellatic acid and the second component is kefir milk (e.g., kefir plain lowfat milk, probiotic mango coconut milk kefir, pure kefir, or ginger turmeric kefir).

Urolithin Compounds [0190] The present disclosure also relates to a composition comprising a compound of formula (I):

wherein Ri, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof, prepared by a method comprising:

(i) combining (a) a first component selected from the group consisting of pomegranate extract, pomegranate juice, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a second component comprising one or more probiotic species, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours.

[0191] In some embodiments, the compound of formula (I) is prepared in a yogurt maker.

[0192] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g.,

Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g. , Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis { e.g ., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium

pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0193] In some embodiments, the second component comprises a mixture of

Akkermansia muciniphila, Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc- 37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02,

Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Akkermansia muciniphila, Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus delbrueckii {e.g., Lactobacillus delbrueckii subsp. bulgaricus), Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus casei. In some embodiments, the second component comprises a mixture of Lactobacillus casei, Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus, and Lactobacillus acidophilus. In some embodiments, the second component comprises a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus rhamnosus, Bifidobacterium pseudocatenulatum and Bifidobacterium bifidum. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus La- 14, Bifidobacterium lactis Bl-04, Lactobacillus paracasei Lpc-37, Lactobacillus rhamnosus Lr-32, Bifidobacterium bifidum/lactis Bb-02,

Bifidobacterium pseudocatenulatum INIA P815 and Bifidobacterium longum Bl-05.

[0194] In one aspect, the composition may comprise urolithin A at greater than about 0.01%, or greater than about 0.025%, or greater than about 1.0%, or greater than about 5.0%, or greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by total weight of the compounds of Formula (I). In some embodiments, the composition produced by the method described herein comprises urolithin A at less than 0.5%, or less than 1.0%, or less than 5.0%, or less than 10%, or less than about 20%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by total weight of the compounds of Formula

(I)·

[0195] In another aspect, the composition may comprise urolithin B at greater than about 0.01%, or greater than about 0.025%, or greater than about 1.0%, or greater than about 5.0%, or greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by total weight of the compounds of Formula (I). In some embodiments, the composition produced by the method described herein comprises urolithin B at less than 0.5%, or less than 1.0%, or less than 5.0%, or less than 10%, or less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by total weight of the compounds of Formula (I).

[0196] In another aspect, the composition may comprise a combination of urolithin A and urolithin B at greater than about 0.5%, or greater than about 2.0%, or greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 40%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by total weight of the compounds of Formula (I). In some embodiments, the composition produced by the method described herein comprises a combination of urolithin A and urolithin B at less than 0.5%, or less than 1.0%, or less than 5.0%, or less than 10%, or less than 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%, or less than about 55%, or less than about 60%, or less than about 65%, or less than about 70%, or less than about 75%, or less than about 80%, or less than about 85%, or less than about 90%, or less than 95% by total weight of the compounds of Formula (I).

[0197] In some embodiments, the second component is absent from the method and the method comprises combining the first component and one or more additional components as described herein. In some embodiments, the one or more additional components comprises a prebiotic fiber milk. In some embodiments, the one or more additional components comprises kefir.

[0198] Also provided herein is a composition comprising a compound of formula (I):

wherein Ri, R2, R3, R4, Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof, prepared by a method comprising:

(i) combining (a) a first component selected from the group consisting of pomegranate extract, pomegranate juice, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a prebiotic component, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

[0199] In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours. In some embodiments, the prebiotic component comprises prebiotic fiber. In some embodiments, the prebiotic fiber can be obtained from one or more of bananas, onions, garlic, Jerusalem artichoke, apples, chicory root, oatmeal, asparagus, dandelion greens, barley and beans. In some embodiments, the prebiotic component comprises kefir. In some embodiments, the first component is ellatic acid and the second component is kefir milk (e.g., kefir plain lowfat milk, probiotic mango coconut milk kefir, pure kefir, or ginger turmeric kefir).

[0200] In some embodiments, the composition may be subject to downstream purification to produce UA or UB, and/or packaging. Downstream purification can be accomplished by any processes known in the art, including but not limited to, filtration, centrifugation, extraction, crystallization, chromatography and distillation. In some embodiments, the composition or the purified compounds are further concentrated. In some embodiments, the concentrated compounds have a concentration at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7- fold, 8-fold, 9-fold, lO-fold, 20-fold, 30-fold, 50-fold, 75-fold, or lOO-fold higher than the concentration prior to the concentration step. In some embodiments, the compositions or the purified compounds may be subject to downstream formulation. In some embodiments, the compositions or the purified compounds are formulated in the form of a food product or a dietary supplement.

[0201] In another aspect, the purity of the urolithin A or urolithin B after purification in the composition is greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than about 40%, or greater than about 45%, or greater than about 50%, or greater than about 55%, or greater than about 60%, or greater than about 65%, or greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85%, or greater than about 90%, or greater than 95% by total weight of the compounds of Formula (I).

[0202] The composition described herein may be used for treatment or prevention of a mitochondrial disease or condition or for maintenance or enhancement of metabolic rates.

Treatment

[0203] The present disclosure also relates to a method for treatment or prevention of a mitochondrial disease or condition or maintenance or enhancement of metabolic rates. The method comprises administering to a subject in need thereof a composition comprising:

(a) a first component selected from the group consisting of pomegranate extract, pomegranate juice, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a second component comprising one or more probiotic species.

[0204] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g.,

Lactobacillus acidophilus La- 14 and Lactobacillus acidophilus LA85), Lactobacillus plantarum {e.g., Lactobacillus plantarum Lp90), Lactobacillus rhamnosus {e.g.,

Lactobacillus rhamnosus Lr-32 and Lactobacillus rhamnosus LRa05), Lactobacillus reuteri {e.g., Lactobacillus reuteri LR08), Lactobacillus casei {e.g., Lactobacillus casei LC89), Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius {e.g. ^

Lactobacillus salivarius LS97), Lactobacillus fermentum {e.g., Lactobacillus fermentum LF15), Lactobacillus crispatus {e.g. , Lactobacillus crispatus LCr86), Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis {e.g.,

Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g. , Bifidobacterium longum Bl-05, B. longum BL21 and B. longum infantis BI45), Bifidobacterium pseudocatenulatum (e.g. , Bifidobacterium pseudocatenulatum INIA P815), Ellagibacter isourolithinifaciens (e.g., Ellagibacter isourolithinifaciens DSM 104140), Enterorhabdus musicola DSM 19490 (e.g., Enterorhabdus musicola DSM 19490), Enterorhabdus caecimuris (e.g., Enterorhabdus caecimuris DSM 21839), Adlercreutzia equolifaciens (e.g., Adlercreutzia equolifaciens DSM 19450), Asaccharobacter celatus (e.g., Asaccharobacter celatus DSM 18785), Parvibacter caecicola (e.g. , Parvibacter caecicola DSM 22242), Gordonibacter urolithinfaciens (CEB AS 1/15P), Gordonibacter pamelaeae (e.g., Gordonibacter pamelaeae 7-lO-l-b) and

Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0205] In some embodiments, the second component comprises a mixture of

Akkermansia muciniphila, Lactobacillus acidophilus (e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus (e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei (e.g., Lactobacillus paracasei Lpc- 37), Lactobacillus salivarius, Bifidobacterium bifidum (e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis (e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum (e.g., Bifidobacterium longum Bl-05), and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus (e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus (e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei (e.g., Lactobacillus paracasei Lpc-37), Bifidobacterium bifidum (e.g., Bifidobacterium bifidum Bb-02,

Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium lactis (e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum (e.g., Bifidobacterium longum Bl-05), and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Akkermansia muciniphila, Lactobacillus acidophilus (e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Bifidobacterium infantis, Bifidobacterium lactis (e.g., Bifidobacterium lactis Bl-04), Bifidobacterium pseudocatenulatum ( e.g ., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus casei. In some embodiments, the second component comprises a mixture of Lactobacillus casei, Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus, Bifidobacterium pseudocatenulatum and Lactobacillus acidophilus. In some embodiments, the second component comprises a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus rhamnosus, and Bifidobacterium bifidum. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus La-l4, Bifidobacterium lactis Bl-04, Lactobacillus paracasei Lpc-37,

Lactobacillus rhamnosus Lr-32, Bifidobacterium bifidum/lactis Bb-02, Bifidobacterium pseudocatenulatum INIA P815 and Bifidobacterium longum Bl-05. In some embodiments, the second component comprises one or more of Ellagibacter isourolithinifaciens (e.g., Ellagibacter isourolithinifaciens DSM 104140), Enterorhabdus musicola DSM 19490 (e.g., Enterorhabdus musicola DSM 19490), Enterorhabdus caecimuris (e.g. , Enterorhabdus caecimuris DSM 21839), Adlercreutzia equolifaciens (e.g., Adlercreutzia equolifaciens DSM 19450), Asaccharobacter celatus (e.g., Asaccharobacter celatus DSM 18785), Parvibacter caecicola (e.g., Parvibacter caecicola DSM 22242), Gordonibacter urolithinfaciens (CEB AS 1/15P) and Gordonibacter pamelaeae (e.g., Gordonibacter pamelaeae 7-lO-l-b).

[0206] In one aspect, the first and second components are formulated and administered as one composition. In some embodiments, the composition further comprises a

pharmaceutically acceptable salt. In some embodiments, the composition is in the form of a food product or a dietary supplement. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier, excipient, binder or diluent. The compositions provided herein may be administered by a suitable route of delivery, such as oral or parenteral. For oral administration, the compositions may be provided in a solid form, such as a tablet or capsule, or as a solution, emulsion, or suspension.

[0207] In another aspect, the first and second components are formulated individually and administered simultaneously. In some embodiments, the method comprises a pharmaceutical composition comprising the first component and a pharmaceutically acceptable carrier, excipient, binder or diluent. In some embodiments, the method comprises a pharmaceutical composition comprising the second component and a pharmaceutically acceptable carrier, excipient, binder or diluent.

[0208] In another aspect, the composition further comprises an additional component such as a lipid. The additional component (e.g., lipid) includes, but is not limited to, fish oil or a salt thereof, algal oil, eicosapentaenoic acid or a salt or ester thereof, docosahexaenoic acid or a salt or ester thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, or a mixture thereof. In some embodiments, the lipid is formulated with the first component. In some embodiments, the lipid is formulated with the second component.

[0209] In some embodiments, the additional component comprises one or more type of milk. In some embodiments, the milk is a nutrient-rich liquid food produced by the mammary glands of mammmals. In some embodiments, the milk is a non-mammalian milk manufactured from a plant extract, wheats, seeds or nuts. The one or more type of milk includes, but is not limited to, human milk, cow milk, goat milk, rice milk, oat milk, hemp milk, soy milk, buckwheat milk, amaranth milk, quinoa milk, chia milk, sorghum milk, tapioca milk, millet milk, teff milk, walnut milk, pistachio milk, pecan milk, hazelnut milk, almond milk, cashew milk, flax milk, and coconut milk. The milk can be whole milk, partly skimmed milk, skim milk, buttermilk, raw or unpasteurized milk, calcium fortified milk, filtered milk, lactose-free milk, milk with DHA (/. <? ., docosahexaenoic acid), omega-3 milk, organic milk, prebiotic fiber milk, evaporated milk, condensed milk, powdered milk, or UHT milk (/. <? ., Ultra High-Temperature Preseurization). In some embodiments, the milk is gluten- free. In some embodiments, the additional component comprises kefir. In some

embodiments, the kefir is vegan kefir or organic kefir.

[0210] In another aspect, the composition further comprises formula (e.g., baby or toddler formula). The formula may include, without limitation, milk formula, dairy-free formula, soy-free formula, lactose-free formula, or vegan formula. In some embodiments, the additional component comprises inulin or walnut.

[0211] In another aspect, the composition further comprises a sugar. In some

embodiments, the sugar is selected from the group consisting of glucose, fructose, N- acetylglucos amine, galactose, sucrose, mannose, maltose, and lactose. In some

embodiments, the sugar is in the form of a syrup. [0212] In other aspect, the composition further comprises a bacteriophage, including, without limitation, Myoviridae (e.g., LH01 - Myoviridae, T4D - Myoviridae, and LL12 - Myoviridae ), Siphorviridae (e.g., LL5 - Siphorviridae) or Bacteriophage PBC1.

[0213] In other aspect, the first and second components are formulated individually and administered sequentially. In some embodiments, the first and second components are administered via different routes. In some embodiments, the first and second components are administered via the same route. In some embodiments, the administration of the first component and the administration of the second component are from 1-30 mins, 30-60 mins, 60-120 mins, 120-180 mins, 180-240 mins, 240-300 mins, or 300-600 mins apart. In some embodiments, the first component is administered before the second component. In some embodiments, the second component is administered before the first component. In some embodiments, the first component is formulated as a pill, tablet, or capsule, while the second component is formulated as a solution or suspension. In some embodiments, the first component is formulated as a solution or suspension, while the second component is formulated as a pill, tablet, or capsule. In some embodiments, the first component is formulated as a food product, while the second component is formulated as a food additive.

In some embodiments, the first component is formulated as a food additive, while the second component is formulated as a food product. In some embodiments, the first component is formulated as a dietary supplement, while the second component is formulated as a food product. In some embodiments, the first component is formulated as a dietary supplement, while the second component is formulated as a dietary supplement.

[0214] In another aspect, the first or second component can be formulated as any pharmaceutical composition described herein. In another aspect the first and/or second component can be formulated as a yogurt.

[0215] In some embodiments, the first and second components are provided as a kit.

[0216] In another aspect, the dosage regimen of the first component is about 1-1000 mg/day, 1000-2000 mg/day, 2000-3000 mg/day, 3000-4000 mg/day, 4000-5000 mg/day, 1- 100 mg/day, 100-200 mg/day, 200-300 mg/day, 300-400 mg/day, 400-500 mg/day, 500-600 mg/day, 600-700 mg/day, 700-800 mg/day, 800-900 mg/day, 900-1000 mg/day, 1000-1100 mg/day, 1100-1200 mg/day, 1200-1300 mg/day, 1300-1400 mg/day, 1400-1500 mg/day, 1500-1600 mg/day, 1600-1700 mg/day, 1700-1800 mg/day, 1800-1900 mg/day, 1900-2000 mg/day, 2000-2100 mg/day, 2100-2200 mg/day, 2200-2300 mg/day, 2300-2400 mg/day, 2400-2500 mg/day, 2500-2600 mg/day, 2600-2700 mg/day, 2700-2800 mg/day, 2800-2900 mg/day, 2900-3000 mg/day, 3000-3100 mg/day, 3100-3200 mg/day, 3200-3300 mg/day, 3300-3400 mg/day, 3400-3500 mg/day, 3500-3600 mg/day, 3600-3700 mg/day, 3700-3800 mg/day, 3800-3900 mg/day, 3900-4000 mg/day, 4000-4100 mg/day, 4100-4200 mg/day, 4200-4300 mg/day, 4300-4400 mg/day, 4400-4500 mg/day, 4500-4600 mg/day, 4600-4700 mg/day, 4700-4800 mg/day, 4800-4900 mg/day, 4900-5000 mg/day, 1-50 mg/day, 50-100 mg/day, 100-150 mg/day, 150-200 mg/day, 200-250 mg/day, 250-300 mg/day, 300-350 mg/day, 350-400 mg/day, 400-450 mg/day, 450-500 mg/day, 500-550 mg/day, 550-600 mg/day, 600-650 mg/day, 650-700 mg/day, 700-750 mg/day, 750-800 mg/day, 800-850 mg/day, 850-900 mg/day, 900-950 mg/day, 950-1000 mg/day, 1000-1050 mg/day, 1050-

1100 mg/day, 1100-1150 mg/day, 1150-1200 mg/day, 1200-1250 mg/day, 1250-1300 mg/day, 1350-1400 mg/day, 1400-1450 mg/day, 1450-1500 mg/day, 1500-2500 mg/day, or 2500-5000 mg/day for 1-7 days, 1-14 days, 1-60 days 1-120 days, 21-240 days, or 120-364 days. In some embodiments, the dosage regimen of the first component is about 5-10 g/day, 10-20 g/day, 20-30 g/day, 30-40 g/day, 40-50 g/day, 50-75 g/day or 75-100 g/day.

[0217] In some embodiments, the dosage regimen of the second component is at about 1- 1000 million CFU/day, 1000-2000 million CFU /day, 2000-3000 million CFU /day, 3000- 4000 million CFU /day, 4000-5000 million CFU /day, 1-100 million CFU /day, 100-200 million CFU /day, 200-300 million CFU /day, 300-400 million CFU /day, 400-500 million CFU /day, 500-600 million CFU /day, 600-700 million CFU /day, 700-800 million CFU /day, 800-900 million CFU /day, 900-1000 million CFU /day, 1000-1100 million CFU /day, 1100- 1200 million CFU /day, 1200-1300 million CFU /day, 1300-1400 million CFU /day, 1400- 1500 million CFU /day, 1500-1600 million CFU /day, 1600-1700 million CFU /day, 1700- 1800 million CFU /day, 1800-1900 million CFU /day, 1900-2000 million CFU /day, 2000- 2100 million CFU /day, 2100-2200 million CFU /day, 2200-2300 million CFU /day, 2300- 2400 million CFU /day, 2400-2500 million CFU /day, 2500-2600 million CFU /day, 2600- 2700 million CFU /day, 2700-2800 million CFU /day, 2800-2900 million CFU /day, 2900- 3000 million CFU /day, 3000-3100 million CFU /day, 3100-3200 million CFU /day, 3200- 3300 million CFU /day, 3300-3400 million CFU /day, 3400-3500 million CFU /day, 3500- 3600 million CFU /day, 3600-3700 million CFU /day, 3700-3800 million CFU /day, 3800- 3900 million CFU /day, 3900-4000 million CFU /day, 4000-4100 million CFU /day, 4100- 4200 million CFU /day, 4200-4300 million CFU /day, 4300-4400 million CFU /day, 4400- 4500 million CFU / day, 4500-4600 million CFU /day, 4600-4700 million CFU /day, 4700- 4800 million CFU /day, 4800-4900 million CFU /day, 4900-5000 million CFU /day, 5000- 6000 million CFU / day, 6000-8000 million CFU / day, 8000-10000 million CFU / day, 1-10 billion CFU/day, 10-50 billion CFU/day, 50-100 billion CFU /day, 100-150 billion CFU /day, 150-200 billion CFU /day, 200-250 billion CFU /day, 250-300 billion CFU /day, 300- 350 billion CFU /day, 350-400 billion CFU /day, 400-450 billion CFU /day, 450-500 billion CFU /day, 500-550 billion CFU /day, 550-600 billion CFU /day, 600-650 billion CFU /day, 650-700 billion CFU /day, 700-750 billion CFU /day, 750-800 billion CFU /day, 800-850 billion CFU /day, 850-900 billion CFU /day, 900-950 billion CFU /day, 950-1000 billion CFU /day, 1000-2000 billion CFU /day, 2000-3000 billion CFU /day, 3000-4000 billion CFU /day, or 4000-5000 billion CFU /day for 1-7 days, 1-14 days, 1-60 days 1-120 days, 21-240 days, or 120-364 days.

[0218] In another aspect, the ratio of the weight of the first component to the weight of viable probiotic species in the second component is at about 1: 1 to 5:1, about 5: 1 to 10:1, about 10:1 to 15:1, about 15: 1 to 20:1, about 20:1 to 25:1, about 25:1 to 50:1, or about 50: 1 to 100:1. In some embodiments, the ratio is about 6: 1 to 7:1. In some embodiments, the ratio is about 1:1 to 25:1.

[0219] In some embodiments, the second component is absent from the method and the method comprises administering to the subject the first component and one or more additional components as described herein. In some embodiments, the one or more additional component comprises a prebiotic fiber milk. In some embodiments, the one or more additional components comprises kefir.

[0220] The present disclosure also relates to a method for treatment or prevention of a mitochondrial disease or condition or maintenance or enhancement of metabolic rates. The method comprises administering to a subject in need thereof a composition comprising:

(a) a first component selected from the group consisting of pomegranate extract, pomegranate juice, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and

(b) a prebiotic component. [0221] In some embodiments, the prebiotic component comprises prebiotic fiber. In some embodiments, the prebiotic fiber can be obtained from one or more of bananas, onions, garlic, Jerusalem artichoke, apples, chicory root, oatmeal, asparagus, dandelion greens, barley and beans. In some embodiments, the prebiotic component comprises kefir. In some embodiments, the first component is ellatic acid and the second component is kefir milk (e.g., kefir plain lowfat milk, probiotic mango coconut milk kefir, pure kefir, or ginger turmeric kefir).

[0222] The present disclosure also relates to a method of for treatment or prevention of a mitochondrial disease or condition or maintenance or enhancement of metabolic rates, the method comprising administering to a subject in need thereof a composition comprising a compound of formula (I):

[0223] wherein Ri, R 2 , R3, R4, R5, R 6 , R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof, wherein the compound of formula (I) is prepared by a method comprising:

(i) combining (a) a first component selected from the group consisting of

pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a second component comprising one or more probiotic species, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours.

[0224] In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Akkermansia, and Saccharomyces. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Lactobacillus, Bifidobacterium, Akkermansia, and Streptococcus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus (e.g. ,

Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g. , Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium inf antis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium

pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises one or more probiotic species selected from the group consisting of Akkermansia muciniphila, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium pseudocatenulatum and Bifidobacterium breve.

[0225] In some embodiments, the second component comprises a mixture of

Akkermansia muciniphila, Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc- 37), Lactobacillus salivarius, Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum {e.g., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La- 14), Lactobacillus plantarum, Lactobacillus rhamnosus {e.g., Lactobacillus rhamnosus Lr-32), Lactobacillus reuteri, Lactobacillus casei, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus paracasei {e.g., Lactobacillus paracasei Lpc-37), Bifidobacterium bifidum {e.g., Bifidobacterium bifidum Bb-02,

Bifidobacterium bifidum/lactis Bb-02), Bifidobacterium breve, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), Bifidobacterium longum {e.g., Bifidobacterium longum Bl-05), Bifidobacterium pseudocatenulatum { e.g ., Bifidobacterium pseudocatenulatum INIA P815) and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Akkermansia muciniphila, Lactobacillus acidophilus {e.g., Lactobacillus acidophilus La-l4), Lactobacillus plantarum, Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Bifidobacterium infantis, Bifidobacterium lactis {e.g., Bifidobacterium lactis Bl-04), and Streptococcus thermophilus. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus casei. In some embodiments, the second component comprises a mixture of Lactobacillus casei, Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus, Bifidobacterium pseudocatenulatum and Lactobacillus acidophilus. In some embodiments, the second component comprises a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus rhamnosus, and Bifidobacterium bifidum. In some embodiments, the second component comprises a mixture of Lactobacillus acidophilus La-l4, Bifidobacterium lactis Bl-04, Lactobacillus paracasei Lpc-37,

Lactobacillus rhamnosus Lr-32, Bifidobacterium bifidum/lactis Bb-02, and Bifidobacterium longum Bl-05.

[0226] The method may further comprise a step of adding a pharmaceutically acceptable carrier, excipient, binder, or diluent following step (ii). A pharmaceutically-acceptable excipient is a substance that is non-toxic and otherwise biologically suitable for

administration to a subject. Such excipients facilitate administration of the compounds described herein and are compatible with the active ingredient. Examples of

pharmaceutically-acceptable excipients include stabilizers, lubricants, surfactants, diluents, anti-oxidants, binders, coloring agents, bulking agents, emulsifiers, or taste-modifying agents.

[0227] The method may further comprise a step of formulating the compound of formula (I) as solutions, emulsions, suspensions, dispersions, or inclusion complexes such as cyclodextrins in suitable pharmaceutical solvents or carriers, or as pills, tablets, lozenges, suppositories, sachets, dragees, granules, powders, powders for reconstitution, or capsules along with solid carriers according to conventional methods known in the art for preparation of various dosage forms. Pharmaceutical compositions provided herein may be administered by a suitable route of delivery, such as oral and parenteral. In some embodiments, the compositions are formulated for intravenous or oral administration.

[0228] For oral administration, the method may comprise formulating the compound in a solid form, such as a tablet or capsule, or as a solution, emulsion, or suspension. To prepare the oral compositions, the compound may be formulated to yield a dosage e.g., from about 1 to about 5 mg/kg daily, or from about 5 to about 10 mg/kg daily, or from about 10 to about 50 mg/kg daily. In some embodiments, one serving of the oral composition comprises the compound at about 100 mg. Oral tablets may include the active ingredient(s) mixed with compatible pharmaceutically acceptable excipients such as diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservative agents. Suitable inert fillers include sodium and calcium carbonate, sodium and calcium phosphate, lactose, starch, sugar, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol, and the like. Exemplary liquid oral excipients include ethanol, glycerol, water, and the like. Starch, polyvinyl-pyrrolidone (PVP), sodium starch glycolate, microcrystalline cellulose, and alginic acid are exemplary disintegrating agents. Binding agents may include starch and gelatin. The lubricating agent, if present, may be magnesium stearate, stearic acid, or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate to delay absorption in the digestive tract (e.g., gastrointestinal tract), or may be coated with an enteric coating.

[0229] Capsules for oral administration include hard and soft gelatin capsules. To prepare hard gelatin capsules, active ingredient(s) may be mixed with a solid, semi-solid, or liquid diluent. Soft gelatin capsules may be prepared by mixing the active ingredient with water, an oil such as peanut oil or olive oil, liquid paraffin, a mixture of mono and di glycerides of short chain fatty acids, polyethylene glycol 400, or propylene glycol.

[0230] Liquids for oral administration may be in the form of suspensions, solutions, emulsions, or syrups, or may be lyophilized or presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid compositions may optionally contain: pharmaceutically-acceptable excipients such as suspending agents (for example, sorbitol, methyl cellulose, sodium alginate, gelatin, hydroxyethylcellulose,

carboxymethylcellulose, aluminum stearate gel and the like); non-aqueous vehicles, e.g., oil (for example, almond oil or fractionated coconut oil), propylene glycol, ethyl alcohol, or water; preservatives (for example, methyl or propyl p-hydroxybenzoate or sorbic acid);

wetting agents such as lecithin; and, if desired, flavoring or coloring agents.

[0231] In another aspect, the composition further comprises a lipid. The lipid includes, but is not limited to, fish oil or a salt thereof, algal oil, chia seed oil, black cumin oil, red grape seed oil, red raspberry seed oil, cranberry seed oil, pumpkin seed oil, eicosapentaenoic acid or a salt or ester thereof, docosahexaenoic acid or a salt or ester thereof, ethyl eicosapentaenoic acid or a salt or ester thereof, omega-3 acid ethyl ester, or a mixture thereof.

[0232] In another aspect, the composition further comprises a sugar. In some

embodiments, the sugar is selected from the group consisting of glucose, fructose, N- acetylglucos amine, galactose, sucrose, mannose, maltose, and lactose. In some

embodiments, the sugar is in the form of a syrup.

[0233] The composition may further comprise one or more milk. In some embodiments, the milk is a nutrient-rich liquid food produced by the mammary glands of mammmals. In some embodiments, the milk is a non-mammalian milk manufactured from a plant extract, wheats, seeds or nuts. The one or more type of milk includes, but is not limited to, human milk, cow milk, goat milk, rice milk, oat milk, hemp milk, soy milk, buckwheat milk, amaranth milk, quinoa milk, chia milk, sorghum milk, tapioca milk, millet milk, teff milk, walnut milk, pistachio milk, pecan milk, hazelnut milk, almond milk, cashew milk, flax milk, and coconut milk. The milk can be whole milk, partly skimmed milk, skim milk, buttermilk, raw or unpasteurized milk, calcium fortified milk, filtered milk, lactose-free milk, milk with DHA (/. <? ., docosahexaenoic acid), omega-3 milk, organic milk, prebiotic fiber milk, evaporated milk, condensed milk, powdered milk, or UHT milk (/. <? ., Ultra High-Temperature Preseurization). In some embodiments, the milk is gluten-free. In some embodiments, the additional component comprises kefir. In some embodiments, the kefir is vegan kefir or organic kefir.

[0234] In another aspect, the composition further comprises a bacteriophage, including, without limitation, Myoviridae (e.g., LH01 - Myoviridae, T4D - Myoviridae, and LL12 - Myoviridae ), Siphorviridae (e.g., LL5 - Siphorviridae) or Bacteriophage PBC1.

[0235] In some embodiments, the second component is absent from the composition and the composition comprises the first component and one or more additional components as described herein. In some embodiments, the one or more additional components comprises a prebiotic fiber milk. In some embodiments, the one or more additional components comprises kefir.

[0236] The present disclosure also relates to a method of for treatment or prevention of a mitochondrial disease or condition or maintenance or enhancement of metabolic rates, the method comprising administering to a subject in need thereof a composition comprising a compound of formula (I):

wherein Ri, R2, R3, R4, Rs, R6, R7, and Rs are each independently selected from the group consisting of H and -OH, or a salt thereof, wherein the compound of formula (I) is prepared by a method comprising:

(j) combining (a) a first component selected from the group consisting of pomegranate extract, an ellagitannin or a salt thereof, ellagic acid or a salt thereof, and mixtures thereof, and (b) a prebiotic component, and

(ii) incubating the resulting combination of step (i) a temperature of at least 15 °C for at least 1 hour.

[0237] In some embodiments, step (ii) comprises incubating the resulting combination of step (i) a temperature of at least 30 °C for at least 8 hours. In some embodiments, the prebiotic component comprises prebiotic fiber. In some embodiments, the prebiotic fiber can be obtained from one or more of bananas, onions, garlic, Jerusalem artichoke, apples, chicory root, oatmeal, asparagus, dandelion greens, barley and beans. In some embodiments, the prebiotic component comprises kefir. In some embodiments, the first component is ellatic acid and the second component is kefir milk (e.g., kefir plain lowfat milk, probiotic mango coconut milk kefir, pure kefir, or ginger turmeric kefir).

[0238] In some embodiments, the composition may be subject to downstream purification to produce UA or UB. Downstream purification can be accomplished by any processes known in the art, including but not limited to, filtration, centrifugation, extraction, crystallization, chromatography and distillation. In some embodiments, the composition or the purified compounds are further concentrated. In some embodiments, the concentrated compounds have a concentration at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, lO-fold, 20-fold, 30-fold, 50-fold, 75-fold, or lOO-fold higher than the concentration prior to the concentration step. In some embodiments, the compositions or the purified compounds may be subject to downstream formulation and/or packaging.

[0239] In some embodiments, the compositions or the purified compounds are formulated in the form of a food product or a dietary supplement. In some embodiments, the composition is administered as a yogurt. In some embodiments, the yogurt is administered in the amount of about 50 g, about 75 g, about 100 g, about 150 g, about 200 g, about 250 g, about 300 mg, about 400 g, about 500 g, about 600 g, about 700 g, about 800 g, about 900 g, or about 1000 g per day. In some embodiments, the yogurt is administered in the amount of about 50-1000 g, about 50-100 g, about 100-250 g, about 250-500 g, about 500-750 g, or about 750-1000 g per day.

[0240] In some embodiments, the composition or the purified compound is administered as an oral tablet or capsule. In some embodiments, the purified compound is UA. In some embodiments, UA is administered in the amount of about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, or about 1000 mg per day. In some embodiments, UA is administered in the amount of about 25-1000 mg, about 25-100 mg, about 100-250 mg, about 250-500 mg, about 500-750 mg, or about 750- 1000 mg per day. In some embodiments, the purified compound is UB. In some

embodiments, UB is administered in the amount of about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, or about 1000 mg per day. In some embodiments, UB is administered in the amount of about 25-1000 mg, about 25-100 mg, about 100-250 mg, about 250-500 mg, about 500-750 mg, or about 750- 1000 mg per day.

[0241] In another aspect, a subject may be a mammalian patient (such as an animal or a human), a nematode, a fungus, a eukaryotic cell or a bacterium. In some embodiments, the subject is c. elegans or yeast. [0242] In another aspect, the disease or condition includes deficiency in muscle growth or muscle performance and mitochondrial diseases, including, but not limited to, aging, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis;

neurodegenerative disorders, such as Huntington’s disease, AIDS dementia complex, adrenoleukodystrophy, Alexander disease, Alper’s disease, Batten disease, Bovine spongiform encephalopathy, ataxia telangiectasia, Canavan disease, corticobasal

degeneration, Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, Lyme disease, and multiple sclerosis; metabolic disorders, such as diabetes, obesity, insulin resistance, and a metabolic syndrome, or any combination thereof.

[0243] In some embodiments, the mitochondrial disease or disorder is aging, diabetes, obesity and neurodegenerative disease. Neurodegenerative diseases include, but are not limited to, Alzheimer's disease, Amyotrophic lateral sclerosis, Friedreich's ataxia,

Huntington's disease, Lewy body disease, Parkinson's disease, Spinal muscular atrophy.

[0244] In some embodiments, the mitochondrial disease or disorder is a neuromuscular disorder, a disorder of neuronal instability, a neurodegenerative disorder, or a mitochondrial myopathy. In yet further embodiments, the mitochondrial disease or disorder is Friedrich’s Ataxia, muscular dystrophy, multiple sclerosis, seizure disorders, migraine, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, ischemia, renal tubular acidosis, age-related neurodegeneration and cognitive decline, chemotherapy fatigue, age-related or chemotherapy-induced menopause or irregularities of menstrual cycling or ovulation, mitochondrial myopathies, mitochondrial damage (e.g., calcium accumulation, excitotoxicity, nitric oxide exposure, drug induced toxic damage or hypoxia), mitochondrial deregulation, Creutzfeldt- Jakob disease, dementia with Lewy bodies, fatal familial insomnia, multiple system atrophy, Huntington’s disease, Kennedy’s disease, frontotemporal lobar degeneration, Machado-Joseph disease, Krabbe disease, neuroacanthocytosis, Pick’s disease, Niemann-Pick disease, progressive supranuclear palsy, primary lateral sclerosis, Sandhoff disease, diffuse myelinoclastic sclerosis, Refsum disease, spinocerebellar ataxia, tabes dorsalis, subacute combined degeneration of spinal cord, Tay-Sachs disease, transmissible spongiform encephalopathy, wobbly hedgehog syndrome, toxic encephalopathy, Barth syndrome, beta- oxidation defects, camitine-acyl-camitine deficiency, carnitine deficiency, creatine deficiency syndrome, co-enzyme Q10 deficiency, complex I deficiency, complex II deficiency, complex III deficiency, complex IV deficiency, complex V deficiency, chronic progressive external ophthalmoplegia syndrome, CPT I deficiency, CPT II deficiency, Kearns-Sayre syndrome, lactic acidosis, leukodystrohpy, Leigh disease, Luft disease, mitochondrial

encephalomyopathy lactic acidosis and stroke-like episodes (MELAS), progeria, Cockayne syndrome, myoclonic epilepsy and ragged-red fiber disease (MERRF), mitochondrial recessive ataxia syndrome, mitochondrial cytopathy, mitochondrial DNA depletion, mitochondrial encephalopathy, myoneurogastointestinal disorder and encephalopathy, neuropathy, ataxia, and retinitis pigmentosa, Pearson syndrome, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency, POLG2 mutations, encephalopathy and possibly liver disease or cardiomyopathy, acyl-CoA dehydrongenase deficiency or any combination thereof.

[0245] In some embodiments, the disease is a disease associated with dementia. In certain embodiments, the disease associated with dementia is selected from the group consisting of Alzheimer’s disease, vascular dementia, dementia with Lewy bodies (DLB), Parkinson’s disease, frontotemporal dementia, Creutzfeldt- Jakob disease, Normal pressure hydrocephalus, Huntington’s disease and Wernicke-Korsakoff syndrome, and any combination thereof.

[0246] In some embodiments, the disease is a disease associated with deficient cognitive performance. In some embodiments, the disease is anxiety, depression, memory loss, or PTSD.

[0247] In some embodiments, the present disclosure provides methods for maintaining or enhancing muscle performance or muscle growth in a subject. Muscle performance may include, without limitation, the capacity of a muscle or a group of muscles to generate forces to produce, maintain, sustain and modify postures and movements that are prerequisite to functional activity. In some embodiments, the method maintains or enhances muscle strength, muscle endurance, speed, muscle power, maximum muscle length, or oxygen level in muscle. In some embodiments, the method maintains muscle performance after or during physical labor or exercise. In some embodiments, the method reduces muscle fatigue, muscle sourness, or muscle tension after physical labor or exercise. In some embodiments, the method reduces the muscle reaction time after stimulation. In some embodiments, the method increases muscle mass or mitochondrial mass in muscle. In some embodiments, the method maintains or increases the number of myofibrils and rate of protein synthesis. In some embodiments, the method reduces inflammatory response or oxidative stress in muscle. In some embodiments, the subject has a deficiency in muscle performance or muscle growth. In some embodiments, the subject does not have a deficiency in muscle performance or muscle growth.

[0248] The present disclosure is also directed to a method of extending lifespan. In certain embodiments, the method maintains or enhances the heath factors in a subject with respect to body-mass index, physical performance, cardiac health, sexual performance, mental health, diet, or substance uses. Physical performance may include athletic performance and general fitness. Physical performance may refer to the capacity to complete daily activities with enough energy left for recreation and relaxation. Cardiac health may include health of the heart and blood vessels. Mental health may include emotional, psychological, and social well-being.

[0249] The present disclosure is also directed to a method of maintaining or enhancing metabolic rate. The metabolic rate may refer to the rate of metabolism, measured by the amount of energy used or generated by an animal per unit of time. Metabolic rate may include, without limitation, basal metabolic rate, the amount of energy used daily by animals at rest. Metabolic rate is influenced by a subject’s size, weight, activity level, and body surface.

[0250] As used herein, the terms“treat” or“treatment”refer to an approach for obtaining a beneficial or desired result, including clinical results. For purposes of this disclosure, beneficial or desired results include, but are not limited to: reducing the severity of or suppressing the worsening of an existing disease, symptom, or condition, alleviating a symptom and/or diminishing the extent of a symptom and/or preventing a worsening of a symptom associated with a condition, arresting the development of a disease, symptom, or condition, relieving the disease, symptom, or condition, causing regression of the disease, disorder, or symptom (in terms of severity or frequency of negative symptoms), or stopping the symptoms of the disease or condition. Beneficial or desired results can also be slowing, halting, or reversing the progressive course of a disease or condition.

[0251] As used herein, a subject may be a mammalian patient (such as a human or an animal (e.g., cat, dog, cow, rat, mouse, horse, or other domesticated mammal)), a nematode, a fungus, a eukaryotic cell or a bacterium. In some embodiments, the subject is C. elegans or yeast. [0252] In another aspect, the methods provided herein may induce an increase of the number of mitochondria present in the subject (e.g., c. elegans or yeast). In some

embodiments, the increase is greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 40%, or greater than about 50%, or greater than about 60%, or greater than about 70%, or greater than about 80%, or greater than about 90%, or greater than about 100%, or greater than about 250%, or greater than about 500%, or greater than about 750%, or greater than about 1000%, or greater than 2000%. In some

embodiments, the increase is about l0%-25%, about 25%-50%, about 50%-l00%, about l00%-250%, about 250%-500%, about 500%-750%, about 750%-l000%, about 1000%- 1500%, about l500%-2000%, about 10%-100%, about l00%-500%, about 500%-2000%, or about l0%-2000%.

[0253] In another aspect, the methods provided herein may induce growth of the subject (e.g., c. elegans, yeast, or mammal). In some embodiments, the growth is in size of the subject. In some embodiments, the growth is in weight of the subject. In some embodiments, the growth is greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 40%, or greater than about 50%, or greater than about 60%, or greater than about 70%, or greater than about 80%, or greater than about 90%, or greater than about 100%, or greater than about 250%, or greater than about 500%, or greater than about 750%, or greater than about 1000%, or greater than 2000%. In some embodiments, the growth is about l0%-25%, about 25%-50%, about 50%-l00%, about l00%-250%, about 250%-500%, about 500%-750%, about 750%-l000%, about 1000%-1500%, about l500%-2000%, about 10%-100%, about l00%-500%, about 500%-2000%, or about l0%-2000%.

[0254] In another aspect, the methods provided herein may induce an increase of the urolithin levels in the subject (e.g., c. elegans, yeast, or mammal). In some embodiments, the increase is greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 40%, or greater than about 50%, or greater than about 60%, or greater than about 70%, or greater than about 80%, or greater than about 90%, or greater than about 100%, or greater than about 250%, or greater than about 500%, or greater than about 750%, or greater than about 1000%, or greater than 2000%. In some embodiments, the increase is about l0%-25%, about 25%-50%, about 50%-l00%, about l00%-250%, about 250%-500%, about 500%-750%, about 750%-l000%, about 1000%-1500%, about l500%-2000%, about 10%-100%, about l00%-500%, about 500%-2000%, or about l0%-2000%. [0255] In another aspect, the methods provided herein may induce a decrease of the reactive oxygen species (ROS) or a decrease of oxidative stress in the subject (e.g., c.

elegans, yeast, or mammal). Examples of ROS include, without limitation, peroxides, superoxide, singlet oxygen, hydroxyl radicals, and alpha-oxygen. In some embodiments, the ROS is from exogenous sources. In some embodiments, the ROS is from endogenous sources. In some embodiments, the decrease of ROS is greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 40%, or greater than about 50%, or greater than about 60%, or greater than about 70%, or greater than about 80%, or greater than about 90%, or greater than about 100%, or greater than about 250%, or greater than about 500%, or greater than about 750%, or greater than about 1000%, or greater than 2000%. In some embodiments, the decrease of ROS is about l0%-25%, about 25%-50%, about 50%-l00%, about l00%-250%, about 250%-500%, about 500%-750%, about 750%- 1000%, about 1000%- 1500%, about l500%-2000%, about 10%-100%, about l00%-500%, about 500%-2000%, or about l0%-2000%.

[0256] In some embodiments, oxidative stress can be measured by levels of any oxidative stress biomarkers known in the art. Examples of oxidative stress biomarkers include, without limitation, lipid peroxidation (e.g., thiobarbituric acid-reactive substances or oxidized low- density lipoprotein (LDL)), protein oxidation (e.g., protein carbonyls or protein nitration), DNA oxidation (e.g., 8-oxo-7,8-dihydro-2’-deoxyguansine), superoxide dismutase, and glutathione system (e.g., glutathione peroxidase or reduced glutathione). In some embodiments, the level of one or more oxidative stress biomarkers is decreased by greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 40%, or greater than about 50%, or greater than about 60%, or greater than about 70%, or greater than about 80%, or greater than about 90%, or greater than about 100%, or greater than about 250%, or greater than about 500%, or greater than about 750%, or greater than about 1000%, or greater than 2000%. In some embodiments, the level of one or more oxidative stress biomarkers is decreased by about l0%-25%, about 25%-50%, about 50%- 100%, about l00%-250%, about 250%-500%, about 500%-750%, about 750%-l000%, about 1000%-1500%, about l500%-2000%, about 10%-100%, about l00%-500%, about 500%- 2000%, or about l0%-2000%.

[0257] In another aspect, the methods provided herein may induce an increase of muscle mass in the subject (e.g., mammal). In some embodiments, increase is greater than about 10%, or greater than about 20%, or greater than about 30%, or greater than about 40%, or greater than about 50%, or greater than about 60%, or greater than about 70%, or greater than about 80%, or greater than about 90%, or greater than about 100%, or greater than about 250%, or greater than about 500%, or greater than about 750%, or greater than about 1000%, or greater than 2000%. In some embodiments, the increase is about l0%-25%, about 25%- 50%, about 50%-l00%, about l00%-250%, about 250%-500%, about 500%-750%, about 750%-l000%, about 1000%-1500%, about l500%-2000%, about 10%-100%, about 100%- 500%, about 500%-2000%, or about l0%-2000%. In some embodiments, the subject is human.

EXAMPLES

[0258] The following examples are offered to illustrate but not to limit the invention. One of skill in the art will recognize that the following procedures may be modified using methods known to one of ordinary skill in the art.

Example 1: Biosynthetic preparation of urolithins with cow milk, goat milk, hemp milk, cashew milk, and coconut milk

[0259] Materials: Ellagic acid 90% Pomegranate Extract was obtained from PureBulk. Whole, raw, and organic milk was obtained from Organic Pastures, and was unpasteurized and non-homogenized. Organic, lactose-free, whole milk was obtained from Horizon and pasteurized with added vitamin D. Probiotic Blend (PB) containing Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, L. salivarius, B. bifidum, B. longum, L.

rhamnosus, and Lxasei, was obtained from Nutrition Now PB8. Probiotic yogurt starter, containing L. casei, B. longum, L. bulgaricus, S. thermophilus, and L. acidophilus, was obtained from Yogourmet. Vegan yogurt starter, containing S. thermophilus, L. acidophilus, L. casei, L. delbrueckii subsp. bulgaricus, L. rhamnosus, and Bifidobacterium bifidum, was obtained from Cultures for Health. Prebiotic Life Extension (LE) contained Lactobacillus acidophilus La- 14, Bifidobacterium lactis Bl-04, L. paracasei Lpc-37, L. rhamnosus Lr-32, B. bifidum/lactis Bb-02, B. longum Bl-05, LH01 - Myoviridae, T4D - Myoviridae, LL5 - Siphorviridae, and LL12 - Myoviridae was from LifeExtension Florassist and in the form of a liquid capsule of 15 billion CFU/cap. Algae Oil (Nordic Naturals) contained EPA (97.5 mg/softcap), DHA (195

mg/softcap), and other Omega-3 (65 mg/softcap). Fish oil contained EPA (734 mg/softcap) and DHA (267 mg/softcap), and was obtained from GNC High Potency Fish Oil Triple Str.

Intellimune oil containing 2 g of Omega 6 fatty acids/tsp and 1 g of Omega 9 fatty acid/tsp was obtained from Intellimune Nutrients. Coconut creme and coconut milk were obtained from Let’s Do Organic Heavy Coconut Cream (13.5 oz) and Thai Kitchen Organic Coconut Milk (13.66 oz) respectively. Goat milk was obtained from Summerhill Dairy. Hemp milk was obtained by combining 1/4 cup of organic shelled hemp seeds from Manitoba Harvest and 1 teaspoon of organic sugar in 2 cups of filtered water, followed by blending for 2 mins and straining through a sieve. Cashew milk was obtained by soaking raw unsalted cashews for 1-2 hours, followed by draining and rinse; then, the 3/4 cups of soaked cashews were mixed in 3 cups of filtered water and 1.5 tsp of agave nectar. Soy free organic baby formula was obtained from Neocate Infant. Good Belly Pomegranate Blackberry Probiotic Shot, Chobani Pomegranate Yogurt, and Stoneyfield Organic Strawberry Yogurt were used as controls. Organic cane sugar was obtained from Kirkland.

[0260] Methods: The container (ajar) was heated in boiling water for 15 minutes to sterilize. Then milk was heated to about 82 °C then cooled down to about 46 °C. Yogurt starter culture (5g/qt) was added to ½ cup of milk and into batches, followed by pouring into the jar. Ellagic acid, probiotic species, and other components were added and mixed in the jar. The jar was incubated at approximately 21 °C (room temperature) for 14 hours.

[0261] Results:

Table 1. Biosynthetic preparation of UA with cow milk, goat milk, cashew milk, hemp milk, and coconut milk

Example 2: Biosynthetic preparation of urolithins with oat milk

[0262] Materials: in addition to materials indicated in Example 1, steel cut oats were used.

[0263] Methods: Oats were soaked in water for 15 minutes and then drained to dry. Soaked oats were rinsed in water and then optionally combined with 2 medjool dates, 1 tsp of vanilla, and a small pinch of salt. The mixture was kept in water and mixed until smooth. The mixture was then strained through a sieve or nut milk bag for 2-3 times and stored in fridge for 3-4 days at about 2-4 °C. The procedure described in Example 1 was then followed.

[0264] Results:

Table 2. Biosynthetic preparation of UA with oat milk

Example 3. Biosynthetic preparation of urolithins with formula

[0265] Materials: in addition to materials indicated in Example 1, soy based toddler formula was obtained from Baby’s Only Soy Organic Toddler Formula.

[0266] Methods: A procedure analogous to that described in Example 1 was followed. [0267] Results:

Table 3. Biosynthetic preparation of UA with formula

Example 4. Assessment of Safety, Pharmacokinetics, and Pharmacodynamics of

Composition Produced by the Biosynthetic Preparation Method

[0268] Primary Endpoints:

1. Safety profile of the composition produced by the biosynthetic preparation method

2. Pharmacokinetics and pharmacodynamics.

[0269] Study Design

[0270] In this study, safety, pharmacokinetics and pharmacodynamics of the composition produced by the biosynthetic preparation method are investigated. Before receiving the first oral dose of the composition formulated as a dietary supplement or a pharmaceutical composition, but after screening and informed consent, eligible subjects undergo blood and urine samplings on Day 1 to establish baseline levels of urolithin, muscle mass and oxidative stress biomarkers. The composition is prepared using the same method described in Example 1 or Example 2 ( e.g ., Sample #4 in Example 1 or Sample #2 in Example 2). Subsequently, each subject receives one of the following dosages:

1. daily doses of half a serving for 7 days;

2. daily doses of one serving for 7 days;

3. daily doses of two servings for 7 days; 4. daily doses of three servings for 7 days;

5. daily doses of half a serving for 4 weeks;

6. daily doses of one serving for 4 weeks;

7. daily doses of two servings for 4 weeks;

8. daily doses of three servings for 4 weeks.

[0271] Each subject underwent serial blood and urine sampling during daily dosing of the composition. If applicable, each subject goes through a two-week washing period in which no compositions are given before the subject is eligible for testing a different dosage.

[0272] Inclusion/Exclusion Criteria

• Inclusion Criteria:

1. Healthy male or female, age > 18 years.

2. Signed, informed consent.

3. Female of childbearing potential must have negative urine pregnancy test result and must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) during the study and one month thereafter.

4. Healthy as determined by laboratory results and medical history.

5. Agrees to maintain current level of physical activity throughout the study.

6. Agrees to avoid study compounds for 30 days prior to enrollment and during the

study 7.

7. Agrees to avoid nutritional yeast, whey proteins, energy drinks, pomegranate,

pomegranate juice, grapefruit, grapefruit juice and alcohol 7 days prior to enrollment and during study 8. Willingness and ability to comply with scheduled visits, cell phone calls, treatment plans, laboratory tests, and completion of other study procedures as specified in the protocol.

• Exclusion Criteria:

1. Women who were pregnant, breastfeeding, or planning to became pregnant during the course of the trial.

2. Subjects who were smokers

3. Unstable medical conditions as determined by the Investigator

4. Immunocompromised individuals such as subjects that had undergone organ

transplantation or subjects diagnosed with human immunodeficiency virus (HIV)

5. Clinically significant abnormal lab results at screening ( e.g ., AST, ALT or ALP > 2 x ULN, and/or bilirubin > 1 x ULN)

6. Subjects who had planned surgery during the course of the trial

7. History of or current diagnosis of any cancer (except for successfully treated basal cell carcinoma) diagnosed less than 5 years prior to screening. Subjects with cancer in full remission more than 5 years after diagnosis were acceptable

8. History of blood/bleeding disorders

9. Blood donation in the past 2 months

10. Alcohol abuse (>2 standard alcoholic drinks per day) or drug abuse within the past 6 months

11. Participation in a clinical research trial within 30 days prior to randomization

12. Allergy or sensitivity to study supplement ingredients provided during the study 13. Individuals who were cognitively impaired and/or who were unable to give informed consent.

14. Any other condition which in the Investigator's opinion may adversely affect the subject's ability to complete the study or its measures or which may pose significant risk to the subject

[0273] Clinical Data and Sample Collections

• Height, weight, temperature, BP, heart rate, demographics

• Urolithin levels ( e.g ., UA and UB), muscle mass, and oxidative stress biomarkers including lipid peroxidation levels (e.g., thiobarbituric acid-reactive substances or oxidized low-density lipoprotein (LDL)), protein oxidation levels (e.g., protein carbonyls or protein nitration), DNA oxidation levels (e.g., 8-oxo-7,8-dihydro-2’- deoxyguansine), superoxide dismutase levels , and glutathione system (e.g., glutathione peroxidase or reduced glutathione).

• Adverse events

Example 5. Biosynthetic preparation of urolithins with various types of milk and other ingredients

[0274] Materials: Quinoa milk, amaranth milk and buckwheat milk were produced by methods described above. Briefly, they were prepared by combining the corresponding grain or nut with water in a 1:4 ratio by volume, soaking for 24-48 hours, draining completely, placing drained grain or nut into a bloender with fresh water in a 1:3 ratio (for quinoa milk) or 1:4 ratio (for amaranth milk and buckwheat milk) by volume, blending completely, straining, and adding water to desired consistency. Ellagic acid was prepared using pomegranate extract from the hulls. The Probiotic blend contained: 30 billion CFU. B. infantis, B. longum, B. lactis, L. brevis, L. plantarum, L. acidophilus, B. animalis, L. helveticus, L. rhamnosus and Galactoligasaccharide (GOS) 231 mg and was obtained from Lifted Naturals. Inulin was obtained from Blue Weber Agave. [0275] Methods: Jars were sanitized and rinsed. 1 capsule of probiotic blend was added to 500 mL of milk and was mixed. 160 mL of each mixture was poured into a jar and mixed with ellagic acid and inulin. The jar was incubated at 25 °C for 24 hours.

Table 4. Biosynthetic preparation of UA with various types of milk and other ingredients

Example 6. Biosynthetic preparation of urolithins with various types of milk and other ingredients [0276] Methods: A procedure analogous to that described in Example 5 was followed except the incubation was at 37 °C for 48 hours. Hazelnut milk, walnut milk and cashew milk were obtained from Elmhurst (unsweetened).

Table 5. Biosynthetic preparation of UA with various types of milk and other ingredients