MITMESSER SUSAN HAZELS (US)
WO2012055820A1 | 2012-05-03 | |||
WO2017190681A1 | 2017-11-09 | |||
WO2009042230A1 | 2009-04-02 | |||
WO2019046646A1 | 2019-03-07 |
CN109329952A | 2019-02-15 | |||
CA2281355A1 | 2001-02-20 | |||
US20200054690A1 | 2020-02-20 | |||
CN108142767A | 2018-06-12 | |||
CN108741061A | 2018-11-06 | |||
CN109418804A | 2019-03-05 | |||
CN105287671A | 2016-02-03 | |||
CN102823860A | 2012-12-19 |
ANONYMOUS: "Whole Food Fiber Whole Food Fiber Combines Dietary Fiber from Nutrient-Rich Whole Foods", 1 January 2008 (2008-01-01), XP055862865, Retrieved from the Internet
PADERIN NIKITA M ET AL: "The effect of dietary pectins on object recognition memory, depression-like behaviour, and il-6 in mouse hippocampi", JOURNAL OF FUNCTIONAL FOODS, ELSEVIER BV, NL, vol. 43, 16 February 2018 (2018-02-16), pages 131 - 138, XP085368584, ISSN: 1756-4646, DOI: 10.1016/J.JFF.2018.02.015
SHERRY C L ET AL: "Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization", BRAIN, BEHAVIOR AND IMMUNITY, ACADEMIC PRESS, SAN DIEGO, CA, US, vol. 24, no. 4, 1 May 2010 (2010-05-01), pages 631 - 640, XP027000812, ISSN: 0889-1591, [retrieved on 20100206]
CHILDS CAROLINE E. ET AL: "Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study", BRITISH JOURNAL OF NUTRITION, vol. 111, no. 11, 14 June 2014 (2014-06-14), pages 1945 - 1956, XP055863987, ISSN: 0007-1145, DOI: 10.1017/S0007114513004261
CHANDRASEKHAR K. ET AL: "A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults", INDIAN JOURNAL OF PSYCHOLOGICAL MEDICINE, vol. 34, no. 3, 1 July 2012 (2012-07-01), pages 255 - 262, XP055862341, ISSN: 0253-7176, Retrieved from the Internet
ZAHIRUDDIN SULTAN ET AL: "Ashwagandha in brain disorders: A review of recent developments", JOURNAL OF ETHNOPHARMACOLOGY, ELSEVIER IRELAND LTD, IE, vol. 257, 16 April 2020 (2020-04-16), XP086170651, ISSN: 0378-8741, [retrieved on 20200416], DOI: 10.1016/J.JEP.2020.112876
DEY AMITABHA ET AL: "Triethylene glycol-like effects of Ashwagandha (Withania somnifera (L.) Dunal) root extract devoid of withanolides in stressed mice", AYU (MUMBAI), vol. 39, no. 4, 1 January 2018 (2018-01-01), IN, pages 230, XP055864688, ISSN: 0974-8520, DOI: 10.4103/ayu.AYU_219_16
ANSARI FERESHTEH ET AL: "The Effects of Probiotics and Prebiotics on Mental Disorders: A Review on Depression, Anxiety, Alzheimer, and Autism Spectrum Disorders", CURRENT PHARMACEUTICAL BIOTECHNOLOGY, vol. 21, no. 7, 16 June 2020 (2020-06-16), NL, pages 555 - 565, XP055862334, ISSN: 1389-2010, DOI: 10.2174/1389201021666200107113812
BEAR TRACEY L K ET AL: "The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety", ADVANCES IN NUTRITION, vol. 11, no. 4, 1 July 2020 (2020-07-01), United States, pages 890 - 907, XP055862333, ISSN: 2161-8313, Retrieved from the Internet
DALILE BOUSHRA ET AL: "The role of short-chain fatty acids in microbiota-gut-brain communication", NATURE REVIEWS GASTROENTEROLOGY, NATURE PUBLISHING GROUP UK, LONDON, vol. 16, no. 8, 23 May 2019 (2019-05-23), pages 461 - 478, XP036844618, ISSN: 1759-5045, [retrieved on 20190523], DOI: 10.1038/S41575-019-0157-3
XIAO SUWEI ET AL: "Modulation of microbially derived short-chain fatty acids on intestinal homeostasis, metabolism, and neuropsychiatric disorder", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, SPRINGER BERLIN HEIDELBERG, BERLIN/HEIDELBERG, vol. 104, no. 2, 21 December 2019 (2019-12-21), pages 589 - 601, XP036979816, ISSN: 0175-7598, [retrieved on 20191221], DOI: 10.1007/S00253-019-10312-4
LOMBARDI VINCENT C ET AL: "Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease", THE JOURNAL OF NUTRITIONAL BIOCHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 61, 19 April 2018 (2018-04-19), pages 1 - 16, XP085530499, ISSN: 0955-2863, DOI: 10.1016/J.JNUTBIO.2018.04.004
VAGHEF-MEHRABANY ELNAZ ET AL: "Can psychobiotics "mood" ify gut? An update systematic review of randomized controlled trials in healthy and clinical subjects, on anti-depressant effects of probiotics, prebiotics, and synbiotics", CLINICAL NUTRITION, CHURCHILL LIVINGSTONE, LONDON, GB, vol. 39, no. 5, 12 June 2019 (2019-06-12), pages 1395 - 1410, XP086152959, ISSN: 0261-5614, [retrieved on 20190612], DOI: 10.1016/J.CLNU.2019.06.004
TABRIZI AYDIN ET AL: "Psychobiotics, as Promising Functional Food to Patients with Psychological Disorders: A Review on Mood Disorders, Sleep, and Cognition", NEUROQUANTOLOGY, vol. 17, no. 6, 1 January 2019 (2019-01-01), XP055862336, Retrieved from the Internet
PAIVA IGOR HENRIQUE R ET AL: "The role of prebiotics in cognition, anxiety, and depression", EUROPEAN NEUROPSYCHOPHARMACOLOGY, ELSEVIER SIENCE PUBLISHERS BV , AMSTERDAM, NL, vol. 34, 30 March 2020 (2020-03-30), pages 1 - 18, XP086143513, ISSN: 0924-977X, [retrieved on 20200330], DOI: 10.1016/J.EURONEURO.2020.03.006
MARSLAND ET AL., BRAIN, BEHAVIOR, AND IMMUNITY, vol. 64, 2017, pages 208 - 219
MUKHERJI ET AL., CELL, vol. 153, 2013, pages 812 - 827
What is Claimed is: 1. A dietary supplement composition comprising at least two prebiotics selected from a source of pectin, a source of beta-glucan, a source of xylooligosaccharide and Ashwagandha in an amount to increase production of (A) tryptophan or (B) tryptophan and/or at least one of (i) indole, (ii) an indole derivative, (iii) 2,3-pyridinecarboxylic acid (iv) 3-(4-hydroxyphenyl) propionic acid and (v) a short chain fatty acid and/or (C) any other metabolite to brain health in a subject. . The dietary supplement^composition of claim 1, wherein the source of pectin comprises apple pectin. 3. The dietary supplement^composition of claim 1, wherein the source of beta-glucan comprises beta-glucan derived from oats. 4. The dietary supplement^composition of claim 1, wherein the at least two prebiotics comprise the source of pectin, the source of beta-glucan and the source of xylooligosaccharide. 5. The dietary supplement composition of claim 1, wherein the at least two prebiotics comprise the source of pectin, the source of beta-glucan and the Ashwagandha. 6. The dietary supplement composition of claim 1, wherein the at least two prebiotics comprise the source of pectin and the source of beta-glucan. 7. The dietary supplement composition of claim 1, wherein the at least two prebiotics comprise the source of pectin and the source of xylooligosaccharide. 8. The dietary supplement composition of claim 1, wherein the at least two prebiotics comprise the source of beta-glucan and the source of xylooligosaccharide. 9. The dietary supplement composition of claim 1, wherein the at least two prebiotics comprise the source of pectin and the Ashwagandha. 10. The dietary supplement composition of claim 1, wherein the at least two prebiotics comprise the source of beta-glucan and the Ashwagandha. 11. The dietary supplement composition of claim 1, wherein the amount of each prebiotic, if present, in a daily amount, is at least 6 grams of the source of pectin, at least 3 grams of the source of beta-glucan, at least 3 grams of the source of xylooligosaccharide and at least 150 milligrams of the Ashwagandha. 12. A method for improving mood comprising: administering to a subject a daily dose amount of a composition comprising at least one prebiotic selected from a source of pectin, a source of beta-glucan, a source of xylooligosaccharide and Ashwagandha in an amount to increase production of (A) tryptophan or (B) tryptophan and/or at least one of (i) indole, (ii) an indole derivative, (iii) 2,3- pyridinecarboxylic acid (iv) 3-(4-hydroxyphenyl) propionic acid and (v) a short chain fatty and/or (C) any other metabolite relevant to brain health. 13. The method of claim 12, wherein the source of pectin comprises apple pectin. 14. The method of claim 12, wherein the source of beta-glucan comprises beta-glucan derived from oats. 15. The method of claim 12, wherein the wherein the at least one prebiotic includes at least two prebiotics. 16. The method of claim 15, wherein the at least two prebiotics comprise the source of pectin, the source of beta-glucan and the Ashwagandha or the source of pectin, the source of beta glucan and the source of xylooligosaccharides. 17. The method of claim 15, wherein the at least two prebiotics comprise the source of pectin and the source of beta-glucan. 18. The method of claim15, wherein the at least two prebiotics comprise the source of pectin and the source of xylooligosaccharide. 19. The method of claim 15, wherein the at least two prebiotics comprise the source of beta-glucan and the source of xylooligosaccharide. 20. The method of claim 15, wherein the at least two prebiotics comprise the source of pectin and the Ashwagandha. 21. The method of claim 15, wherein the at least two prebiotics comprise the source of beta-glucan and the Ashwagandha. 22. The method of claim 12, wherein the daily dosage amount of each prebiotic, if present, is at least 6 grams of the source of pectin, at least 3 grams of the source of beta- glucan, at least 3 grams of the source of xylooligosaccharide and at least 150 milligrams of the Ashwagandha. |
[0039] Figure 1 shows the effect on gut microbial tryptophan production when human gut microbiota was individually cultured with oats beta-glucan, XOS and apple pectin. Figure 1 shows that an increase in tryptophan production was observed with the addition of oats beta-glucan, XOS and apple pectin. [0040] Figure 2 shows the effect on gut microbial indole production when human gut microbiota was cultured with apple pectin. Figure 3 shows the effect on the production of gut microbial indole derivatives and other microbial metabolites such as 2,3- pyridinecarboxylic acid and 3-(4-hydroxyphenyl) propionic acid when human gut microbiota was cultured with beta-glucan. Figures 2 and 3 show that there was a statistically significant increase in indole production with apple pectin and elevation in the levels of other indole derivatives with beta-glucan addition. [0041] Figure 4 shows the effect on gut microbial short chain fatty acid production when human gut microbiota was cultured individually with apple pectin, beta-glucan, xylooligosaccharides and Ashwagandha. Figure 4 shows there was an increase in the production of most SCFA evaluated (acetate, propionate and butyrate) with addition of each probiotic. Example 2. [0042] It is believed that the gut microbiota acts through direct production of neuroendocrine metabolites (hormone-like metabolites such as short chain fatty acids, neurotransmitters, gastrointestinal hormones, precursors to neuroactive compounds such as tryptophan) and/or, indirectly, as the modulator of inflammatory responses, immune responses and hormonal secretion. [0043] Hypothalamic-Pituitary-Axis (HPA): The anatomical structures that mediate the stress response are found in both the central nervous system and peripheral tissues. The principal effectors of the stress response are localized in the paraventricular nucleus (PVN) of the hypothalamus, the anterior lobe of the pituitary gland, and the adrenal gland. This collection of structures is commonly referred to as the hypothalamic-pituitary-adrenal (HPA) axis. HPA is one of the main neuroendocrine systems in mammals. Activation of the HPA axis is a tightly controlled process that involves a wide array of neuronal and endocrine systems. It is subject to feedback inhibition from circulating glucocorticoids. The HPA axis mounts a defensive response when it perceives a threat which ultimately induces the release of behavior-altering hormones such as glucocorticoids, mineral corticoids and catecholamines. HPA dysfunction is also associated with depression. [0044] Corticosterone: Glucocorticoids, cortisol in humans and corticosterone in rodents, are endogenous steroid hormones secreted by the adrenal glands under the regulation of the HPA and have pleiotropic functions involved in the stress response, energy metabolism, reproductive function, and inflammatory and immune responses. [0045] Cortisol or corticosterone are important mediators of the stress system. The corticosteroid hormones operate in concert with catecholamines and other transmitters. Insufficient corticosteroid control leads to aggravated stress reactions. Alternatively, if adaptation to stress fails, circulating corticosteroid levels remain elevated for a prolonged period of time. Both, too low and too high cortisol/corticosterone concentrations are detrimental for brain processes. [0046] Stress leads to elevation of corticosterone, which then binds to and activates both mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). Since MRs have a higher affinity, these receptors tend to remain occupied even at low, basal levels of corticosterone. In contrast, GRs have a lower affinity for corticosterone; therefore, levels of GR activation tend to correlate with changing levels of free corticosterone. The expression pattern of MRs and GRs differ substantially throughout the brain. MRs are expressed in limbic brain circuits and as well as in the pituitary whereas GRs are more widely expressed throughout the brain. However, GR expression is particularly high in the hypothalamus, hippocampus and the pituitary, suggesting that this receptor plays an important role in regulating the function of the brain cells in these regions. [0047] Stress and Inflammation: A meta-analysis showed statistically significant stress- related increases in circulating interleukins IL-1β, IL-6, IL-10, and tumor necrosis factor (TNF^) but not IL-1ra, IL-2, interferon-c, or C-reactive protein (Marsland et al. Brain, Behavior, and Immunity, 642017, 208–219). Stress responses of inflammatory markers have been found to be higher in individuals with different forms of depression. Laboratory studies showed that acute stress was associated with significant increases in IL-1β, and TNF^ with IL-b, IL-6, and TNF^ demonstrating the most robust increases. Higher cytokine levels were reported to be associated with increases in negative mood and anxiety in some studies. [0048] Gut microbiota also mediates the production of immune mediators such as TNF^, IL-1^ and IL-6 that, in turn, reach the brain and stimulate the HPA axis. Moreover, the gut microbiota is able to directly influence the production of glucocorticoid hormones. Research has shown that the interaction between bacterial products and Toll-like receptors (TLR) expressed on the intestinal epithelium is crucial for maintaining homeostatic levels of corticosterone, in fact microbiota - depleted mice have exaggerated and sustained synthesis of corticosterone throughout the day (Mukherji et al., 2013, Cell 153, 812–827). [0049] Behavior assays in rodents: Several behavioral assays have been developed to study stress, anxiety, and depression in rodents. The forced swim test (FST) measures the presence of or reduction in positive coping skills in rats and mice. When the animals are treated with anti-depressant prior to the test, they show reduced immobility and more climbing, suggesting that the animals do not give up, while untreated animals show increased immobility and will float more in the water. Therefore, reduced immobility and more climbing are thought to be an anti-depressive, positive coping phenotype in the FST. Many tests are based on the fact that normal rodents prefer “unexposed” areas. In the elevated plus maze (EPM) test, the frequency and duration that rodents explore in an exposed environment is measured. Anxiety is analyzed by the average time spent in open arms, closed arms, and the center zone of the maze and reduced time spent on open arms indicates that the animal experienced more anxiety. EXPERIMENTAL DESIGN [0050] This study was designed to evaluate the effect of prebiotic(s) on stress induced anxiety and/or depression. Both behavior and quantitative assessments were done to evaluate physiologically relevant effects. As noted, stress leads to increase in corticosterone and inflammatory cytokines. Resistance to such an increase may lead to positive coping skills and could be seen in behavior tests such as EPM (for anxiety) and FST (for depression). [0051] 13 males and 13 female C57BL/6J mice were recruited to each diet group (Table 2). The animals were given immediate ad libitum access to water and standard rodent chow (control diet) and were acclimated to the facility for 7 days. On study day 0, the animals were weighed, blood and fecal samples (1-2 pellets/animal) were collected, and the animals were randomized by weight into their specific diet and treatment groups that included chow only (control group), chow supplemented with maltodextrin or chow supplemented with one or more prebiotics (Table 2). Blood and fecal collections were done at 0, 4 and 8 weeks. On study day 50, animals assigned to the acute stress groups were acutely restrained for 2 hours while unstressed animals were housed singly for 140 minutes in fresh cages. Following the 2-hour stress period, stressed animals were released into their cage (without bedding) and had a 20-minute grooming break. Similarly, on study days 51 and 52, all animals were stressed as above (or not) and then tested on the respective days in the EPM and FST. A retro-orbital blood sample was collected within 15 to 30 minutes after the FST, and fecal pellets were collected at the end of the experiment. Necropsy was performed on study day 56. Blood and tissues were collected for biochemical analysis. Table 2. Diets used in the Example 2 P = Apple pectin, G = Oats beta glucan, X = Xylooligosaccharides, A = Ashwagandha RESULTS [0052] Endocrine response: Alterations in the hypothalamic–pituitary–adrenal (HPA) axis and stress response has been linked to the development of mood disorders. Serum corticosterone levels were measured after acutely stressed mice underwent FST. After FST, the serum corticosterone levels were increased in stressed female mice and were not reduced by maltodextrin (non-prebiotic) supplementation. However, serum corticosterone levels in female mice were statistically reduced (F(3, 48) >7.1, p <0.0005) in most prebiotic treatment groups (except diets apple pectin/oats beta glucan/xylooligosaccharides (PGX) and apple pectin/oats beta glucan/Ashwagandha (PGA)) as compared to the stressed control and as compared to maltodextrin controls except the diet of apple pectin/oats beta glucan (PG) (Figure 5). Moreover, the levels were reduced to that of the unstressed mice. This suggests that diets of one of apple pectin (P), oats beta glucan (G), xylooligosaccharides (X), Ashwagandha (A), Apple pectin/xylooligosaccharides (PX), oats beta glucan/ xylooligosaccharides (GX), apple pectin/Ashwagandha (PA), oats beta glucan/Ashwagandha (GA) or apple pectin/oats beta glucan (PG) lead to better adaptation to stress response. There was also a greater reduction in oats beta glucan/ xylooligosaccharides (GX) and oats beta glucan/Ashwagandha (GA) as compared to oats beta glucan (G) alone. Male mice did not show the same reduction in corticosterone levels in stressed mice as female mice with prebiotic treatment (data not shown). [0053] Inflammatory cytokine levels: A panel of 16 serum cytokines was analyzed using blood collected after 8 weeks of dietary supplementation at the termination of the experiment. A combined group of male and female mice on the control diet which were stressed acutely during the experiments had higher inflammatory cytokine levels as compared to unstressed control mice. Addition of prebiotic(s) to the diet showed significantly reduced levels for most cytokines as compared to stressed mice indicating potential for reduced systemic inflammation as shown in Table 3 (top panel). Averages of cytokine levels from 26 mice are shown in gray scale with the darkest gray being high levels, white or no-shading being lowest level, and varying shades of gray in between being intermediate levels (the darker the gray, the higher the level of cytokines) and the graphs in Figure 6a, Figure 6b, Figure 6c and Figure 6d. The gray-scale coding in the tables is showing the trends and the graphs have statistical significance compared to controls for each cytokine. Combinations of two or more prebiotics were more effective in reducing the cytokine levels than individual dietary prebiotic treatment as shown in Table 3 (bottom panel) representing averages for cytokines for individual prebiotics, double combinations and triple combinations, which helps visualize the trend. [0054] Surprisingly, treatment with a maltodextrin (DE-13) supplemented diet that was used as non-prebiotic control also showed reduction in inflammatory cytokines, which could be due to a distinct mechanism. Maltodextrin is a polysaccharide derived from starch consisting of D-glucose units linked primarily by ^-1-4 bonds and that has a dextrose equivalent (DE) of less than 20. Commonly, maltodextrin sold in the market has a DE between 3 and 20. The higher the DE value, the shorter the glucose chains. DE > 20 is called glucose syrup. DE13-17 contains more low-molecular glucose units and less high- molecular glucose units. These glucose units may be acted upon by a-amylase, converted to maltose and are rapidly absorbed in the small intestines unlike prebiotics, which remain undigested in upper gastrointestinal tract and are fermented in the colon by gut bacteria.
^ [0055] Anxiety like behavior. In the EPM, female mice on diets supplemented with oats beta glucan (G), oats beta glucan/xylooligosaccharides (GX) and apple pectin/Ashwagandha (PA) demonstrated significantly increased open arm times (F(3, 48) >4.5, p <0.0070) and significantly reduced closed-arm times as compared to the unstressed control group with open arm times for mice on diets oats beta glucan (G) or glucan/xylooligosaccharides (GX) also being significant versus the maltodextrin (non-prebiotic) control group of stressed mice (Figure 7). In the EPM, time spent on open and closed arms for male mice on test diets did not differ statistically from the diet control groups (data not shown). [0056] Depressive like behavior: In the FST, immobility over time did not differ statistically across combined female/male control groups. After acute stress, immobility over time was significantly reduced in combined female/male groups treated with diets supplemented with oats beta glucan (G), oats beta glucan/Ashwagandha (GA), or apple pectin/oats beta glucan (PG) as compared to the unstressed control group (Table 4, Figure 8a, Figure 8b) and was significantly increased in mice on diet X as compared to the stressed control group (Figure 8a). Table 4 shows averages of immobility over time within the groups in gray scale with darkest gray color shading being high immobility, white or no- shading color being lowest level of immobility, and gray shading between darkest and no- shading being intermediate levels with the darker the gray the higher the immobility. Comparison of individual versus combined treatments showed that mice on diets including oats beta glucan (G) or apple pectin (PG) had significantly reduced immobility over time as compared to mice on diets including xylooligosaccharides (X), oats beta glucan/xylooligosaccharides (GX), apple pectin/Ashwagandha (PA), apple pectin/oats beta glucan/xylooligosaccharides (PGX) or apple pectin/oats beta glucan/Ashwagandha (PGA). Immobility was also significantly reduced in mice on diets including Ashwagandha (A) or oats beta glucan/Ashwagandha (GA) as compared to mice on diet including apple pectin/oats beta glucan/Ashwagandha (PGA). Although data was not statistically significant as compared to stressed maltodextrin controls, the trend towards reduced immobility (Table 4) was seen indicating potential for positive coping skills. Table 4. Forced Swim Test (averages)
[0057] The experiment presented in Example 2 shows that [1] all diets supplemented with the noted prebiotics showed statistically significant reduction in corticosterone (the stress hormone) in the female mice except triple combinations of PGA and PGX where the reduction was not statistically significant. [2] All prebiotic supplemented diets individually or in combinations reduced stress induced inflammation in both male and female mice. The results also indicate that there was more reduction in diets supplemented with prebiotic combinations than individual prebiotics. [3] The results of behavior outcomes suggest that prebiotic diets supplemented with oats beta glucan (G) or oats beta glucan/xylooligosaccharides (GX) increased time spent on open arms in the EPM when compared to stressed non-prebiotic maltodextrin controls indicating an increase in exploratory behavior and a reduced anxiety phenotype. This is consistent with reduction in corticosterone levels. [4] The results of behavior outcomes also suggest that reduction in immobility in the FST was observed (diets oats beta glucan (G), oats beta glucan/Ashwagandha (GA), and apple pectin/oats beta glucan (PG) when compared to unrestrained control animals. Although the data was not statistically significant as compared to stressed maltodextrin controls, the trends in reduced immobility were seen indicating potential for positive coping skills. [5] Finally, the results indicate that the effect of prebiotic supplementation was more pronounced in females than males. [0058] The mouse equivalent dose presented in Example 2 for each prebiotic provided to the animals individually or in combination with one or more other prebiotic was calculated based on a target human dose of at least: apple pectin (P) 6 grams/day of an apple pectin source of 90 percent apple pectin by weight; oats beta glucan (G) 3 grams/day of an oats beta glucan source of 85 percent by weight oats beta glucan; xylooligosaccharides (X) 3 grams/day of a xylooligosaccharides source of 90 percent by weight xylooligosaccharides; and Ashwagandha (A) 150 milligrams/day. ASPECTS [0059] Aspect 1. A dietary supplement composition comprising, consisting essentially of or consisting of at least one prebiotic or at least two prebiotics selected from a source of pectin, a source of beta-glucan, a source of xylooligosaccharide and Ashwagandha in an amount to increase production of (A) tryptophan or (B) tryptophan and/or at least one of (i) indole, (ii) an indole derivative, (iii) 2,3-pyridinecarboxylic acid (iv) 3-(4-hydroxyphenyl) propionic acid and (v) a short chain fatty acid. and/or (C) any other metabolite relevant to (e.g., benefitting) brain health (e.g., dopamine, serotonin, GABA) such as improving mood by reducing stress/anxiety/ depression in a subject. [0060] Aspect 2. The dietary supplement composition of Aspect 1, wherein the source of pectin comprises apple pectin. [0061] Aspect 3. The dietary supplement composition of Aspect 1 or Aspect 2, wherein the source of beta-glucan comprises beta-glucan derived from oats. [0062] Aspect 4. The dietary supplement composition of any of Aspects 1-3, wherein when the dietary supplement comprises at least two prebiotics, the at least two prebiotics comprise, consist essentially of or consist of the source of pectin, the source of beta-glucan and the source of xylooligosaccharide. [0063] Aspect 5. The dietary supplement composition of any of Aspects 1-3, wherein when the dietary supplement comprises at least two prebiotics, the at least two prebiotics comprise, consist essentially of or consist of the source of pectin, the source of beta-glucan and the Ashwagandha. [0064] Aspect 6. The dietary supplement composition of any of Aspects 1-3, wherein when the dietary supplement comprises at least two prebiotics, the at least two prebiotics comprise, consist essentially of or consist of the source of pectin and the source of beta- glucan. [0065] Aspect 7. The dietary supplement composition of any of Aspects 1-3, wherein when the dietary supplement comprises at least two prebiotics, the at least two prebiotics comprise pectin and the source of xylooligosaccharide. [0066] Aspect 8. The dietary supplement composition of any of Aspects 1-3, wherein when the dietary supplement comprises at least two prebiotics, the at least two prebiotics comprise, consist essentially of or consist of the source of beta-glucan and the source of xylooligosaccharide. [0067] Aspect 9. The dietary supplement composition of any of Aspects 1-3, wherein when the dietary supplement comprises at least two prebiotics, the at least two prebiotics comprise, consist essentially of or consist of the source of pectin and the Ashwagandha. [0068] Aspect 10. The dietary supplement composition of any of Aspects 1-3, wherein when the dietary supplement comprises at least two prebiotics, the at least two prebiotics comprise, consist essentially of or consist of the source of beta-glucan and the Ashwagandha. [0069] Aspect 11. The dietary supplement composition of any of Aspects 1-10, wherein the amount of each prebiotic, if present, in a daily amount, is at least 6 grams of the source of pectin, such as a source of pectin comprising at least 75 percent or at least 95 percent pectin by weight, at least 3 grams of the source of beta-glucan, such as a source of beta-glucan comprising at least 75 percent or at least 85 percent beta-glucan by weight, at least 3 grams of the source of xylooligosaccharide such as a source of xylooligosaccharide comprising at least 75 percent or at least 90 percent xylooligosaccharide by weight and at least 150 milligrams of the Ashwagandha. [0070] Aspect 12. A method for improving mood (reducing stress/anxiety/depression) comprising: administering to a subject a daily dose amount of a composition, e.g., a dietary supplement composition, comprising, consisting essentially of or consisting of at least one prebiotic selected from a source of pectin, source of beta-glucan, a source of xylooligosaccharide and Ashwagandha in an amount to increase production of (A) tryptophan or (B) tryptophan and/or at least one of (i) indole, (ii) an indole derivative, (iii) 2,3- pyridinecarboxylic acid (iv) 3-(4-hydroxyphenyl) propionic acid and (v) a short chain fatty acid and/or (C) any other metabolite (e.g., dopamine, serotonin, GABA) relevant to (e.g., benefitting) brain health such as improving mood in a subject. [0071] Aspect 13. The method of Aspect 12, wherein the source of pectin comprises apple pectin. [0072] Aspect 14. The method of Aspect 12 or Aspect 13, wherein the source of beta- glucan comprises beta-glucan derived from oats. [0073] Aspect 15. The method of any of Aspects 12-14, wherein the at least one prebiotic comprises, consists essentially of or consists of at least two prebiotics. [0074] Aspect 16. The method of any of Aspects 15, wherein the at least two prebiotics comprise, consist essentially of or consist of the source of pectin, the source of beta-glucan and the Ashwagandha or the source of pectin, the source of beta glucan and the source of xylooligosaccharides.. [0075] Aspect 17. The method of any of Aspects 15, wherein the at least two prebiotics comprise, consist essentially of or consist of the source of pectin and the source of beta- glucan. [0076] Aspect 18. The method of any of Aspects 15, wherein the at least two prebiotics comprise, consist essentially of or consist of the source of pectin and the source of xylooligosaccharide. [0077] Aspect 19. The method of any of Aspects 15, wherein the at least two prebiotics comprise, consist essentially of or consist of the source of beta-glucan and the source of xylooligosaccharide. [0078] Aspect 20. The method of any of Aspects 15, wherein the at least two prebiotics comprise, consist essentially of or consist of the source of pectin and the Ashwagandha. [0079] Aspect 21. The method of any of Aspects 15, wherein the at least two prebiotics comprise, consist essentially of or consist of the source of beta-glucan and the Ashwagandha. [0080] Aspect 22. The method of any of Aspects 12-21, wherein the daily dosage amount of each prebiotic, if present, is at least 6 grams of the source of pectin, such as a source of pectincomprising at least 75 percent or at least 95 percent pectin by weight, at least 3 grams of the source of beta-glucan, such as a source of beta-glucan comprising at least 75 percent or at least 85 percent beta-glucan by weight, at least 3 grams of the source of xylooligosaccharide such as a source of xylooligosaccharide comprising at least 75 percent or at least 90 percent xylooligosaccharide by weight and at least 150 milligrams of the Ashwagandha. [0081] Whereas specific aspects of the invention have been described in detail, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements disclosed are meant to be illustrative only and not limiting as to the scope of the invention which is to be given the full breadth of the claims and aspects appended and any and all equivalents thereof.
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