CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 62/962,815 filed on January 17, 2020, which is herein incorporated by reference in its entirety.

DESCRIPTION OF THE TEXT FILE SUBMITTED ELECTRONICALLY [0002] The contents of the text file submitted electronically herewith are incorporated herein by reference in their entirety: A computer readable format copy of the Sequence Listing filename: 47192-0048W01_SL.txt, date created, January 15, 2021, file size ~ 140 kilobytes.

TECHNICAL FIELD

[0002] The present disclosure is related to bacterial strains and compositions thereof, and using such bacterial strains and compositions thereof for treating cancer in a subject. BACKGROUND

[0003] The human microbiome comprises a diverse array of microorganisms, primarily prokaryotes, which play a significant role in the health of the host organism. The complexity of the microbiome, in terms of both its population makeup and composite function, has recently become an intense area of study as research increasingly shows that manipulation of the microbiome can provide health benefits and may be effective in treating a number of diseases and disorders. Currently, a number of probiotics are marketed which contain live bacteria and yeast and are believed to augment the benefits of these microbes which naturally occur in the human body. Increasingly, live biotherapeutic products (LBPs) are being developed for controlled clinical studies and regulatory approval in the treatment of disease.

[0004] From 2011 to 2018, the estimated percentage of US patients with cancer who are eligible for immune checkpoint inhibitors increased from 1.54% to 43.63%, however, the percentage of patients estimated to respond to immune checkpoint inhibitor drugs was only 0.14% in 2011 and 12.46% in 2018 (see Haslam and Prasad. JAMA Netw Open. 2019 May; 2(5): el92535). Immune checkpoint inhibitor treatment elicits a durable response in a subset of melanoma cancer patients, but up to 70% do not respond adequately to treatment. The composition of the gut microbiome may be one of the factors determining the efficacy of immune checkpoint inhibitor treatment (see, e.g., Yi et al. Hepatobiliary Surg Nutr. 2018 Dec; 7(6): 481-483). For example, the gut microbiome may enhance the function of dendritic cells, decrease regulatory T-cells and myeloid derived suppressor cells, increase trafficking of CD4+ memory T-cells from mesenteric and draining lymph nodes to the tumor microenvironment, as well as increase recruitment and activation of IFN-g- producing tumor-antigen-specific effector T-cells (see Gong et al. Clin Transl Med. 2019; 8: 9). Furthermore, specific commensal bacteria may be associated with immunoregulatory pathways that facilitate immune checkpoint response.

[0005] The exact mechanisms by which the gut microbiome affects the anticancer efficacy of immune checkpoint therapiesremains unclear, and finding consistent associations between clinical responses to immune checkpoint inhibitors and the microbiome has proven difficult. Improved therapies such as microbe-based therapies are desirable.

SUMMARY

[0006] Provided herein are methods of treating cancer in a subject that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or)bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and (b) administering a cancer treatment that excludes an immunomodulator as a monotherapy to the identified subject.

[0007] Also provided herein are methods of treating cancer in a subject that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and (b) administering a therapeutically effective amount of a bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihominis , Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Ruminococcaceae bacterium , Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., Bifidobacterium adolescentis , and a combination thereof, and an immunomodulator as a monotherapy or in conjunction with another anticancer agent to the identified subject. [0008] Also provided herein are methods of treating cancer in a subject that include administering to a subject identified as having (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis , a therapeutically effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp.,

Barnesiella intestinihominis , Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., Bifidobacterium adolescentis 221, and a combination thereof, and an immunomodulatory as a monotherapy or in conjunction with another anticancer agent.

[0009] Also provided herein are methods of treating cancer in a subject that include administering to a subject identified as having (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and

Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis a cancer treatment that excludes an immunomodulatory as a monotherapy.

[0010] Also provided herein are methods of treating a cancer in a subject that has previously received one or more doses of an immunomodulator, wherein the method comprises administering to a subject identified as having: (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis; a cancer treatment that excludes an immunomodulator as a monotherapy.

[0011] Also provided herein are methods of treating a cancer in a subject that has previously received one or more doses of an immunomodulator, wherein the method comprises administering to a subject identified as having: (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis; a therapeutically effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihominis , Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., Bifidobacterium adolescentis 221, and a combination thereof, and an immunomodulator as a monotherapy or in conjunction with another anticancer agent.

[0012] Also provided herein are methods of treating cancer in a subject, the method comprising: (a) administering one or more doses of an immunomodulator for a period of time; (b) after (a), determining whether a sample obtained from a subject having cancer has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and

Bifidobacterium adolescentis ; and (c) administering a therapeutically effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihominis , Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., Bifidobacterium adolescentis 221, and a combination thereof, and an immunomodulator as a monotherapy or in conjunction with another anticancer agent. [0013] Also provided herein are methods for identifying a subj ect as having an decreased likelihood of having a positive response to treatment with an immunomodulator, the method comprising: a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis , as having an decreased likelihood of having a positive response to treatment with an immunomodulator. [0014] In some embodiments of any of the methods provided herein, the level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and

Eisenbergiella massiliensis are increased in comparison to the same bacterial species in a reference sample.

[0015] In some embodiments of any of the methods provided herein, the level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis are decreased in comparison to the same bacterial species in a reference sample.

[0016] In some embodiments of any of the methods provided herein, the level of one or more (e.g., two or more, or three) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., and Streptococcus parasanguinis are increased in comparison to the same bacterial species in a reference sample.

[0017] In some embodiments of any of the methods provided herein, the level of one or more (e.g., two or more, three or more, or four) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , and Oscillibacter sp. are decreased in comparison to the same bacterial species in a reference sample.

[0018] In some embodiments of any of the methods provided herein, the level of one or more bacterial species selected from the group consisting of: Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis are increased in comparison to the same bacterial species in a reference sample. [0019] In some embodiments of any of the methods provided herein, the level of the bacterial species selected from the group consisting of: Barnesiella intestinihominis, Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis is decreased in comparison to the same bacterial species in a reference sample.

[0020] Also provided herein are methods of treating cancer in a subject that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp. , Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and (b) administering an immunomodulator as a monotherapy or in conjunction with another anticancer agent to the subject.

[0021] Also provided herein are methods of treating cancer in a subject that include administering to a subject identified as having (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp. , Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis , a therapeutically effective amount of an immunomodulatory as a monotherapy or in conjunction with another anticancer agent. [0022] Also provided herein are methods for identifying a subject as having an increased likelihood of having a positive response to treatment with an immunomodulator that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis, as having an increased likelihood of having a positive response to treatment with an immunomodulator.

[0023] Also provided herein are methods for selecting an immunomodulator for a subject that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii, Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis, Faecalibacterium prausnitzii, Barnesiella intestinihominis, Clostridiaceae bacterium, Clostridium sp., and Bifidobacterium adolescentis, and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme, Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and selecting an immunomodulator for the identified subject. [0024] Also provided herein are methods for selecting a subject for treatment with an immunomodulator comprising (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and selecting the identified subject for treatment with an immunomodulator.

[0025] Also provided herein are methods for selecting a subject for participation in a clinical study comprising administration of an immunomodulator, (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and selecting the identified subject for participation in a clinical study comprising administration of an immunomodulator. [0026] In some embodiments of any of the methods provided herein, the level of the bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihominis, Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium ,

Clostridium sp., and Bifidobacterium adolescentis are increased in comparison to the same bacterial species in a reference sample.

[0027] In some embodiments of any of the methods provided herein, the level of one or more bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis are decreased in comparison to the same bacterial species in a reference sample.

[0028] In some embodiments of any of the methods provided herein, the level of one or more (e.g. two or more, or three) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., and Streptococcus parasanguinis are decreased in comparison to the same bacterial species in a reference sample.

[0029] In some embodiments of any of the methods provided herein, the level of one or more (e.g. two or more, three or more, or four) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , and Oscillibacter sp. are increased in comparison to the same bacterial species in a reference sample.

[0030] In some embodiments of any of the methods provided herein, the level of one or more bacterial species selected from the group consisting of: Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis are decreased in comparison to the same bacterial species in a reference sample.

[0031] In some embodiments of any of the methods provided herein, the level one or more bacterial species selected from the group consisting of: Barnesiella intestinihominis, Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis is increased in comparison to the same bacterial species in a reference sample.

[0032] In some embodiments of any of the methods provided herein, the method further comprises detecting the level of one or more bacterial species in a sample from the subject. [0033] In some embodiments of any of the methods provided herein, the cancer treatment comprises surgery, radiation therapy, a therapeutic agent, or a combination thereof. In some embodiments of any of the methods provided herein, the therapeutic agent comprises a chemotherapeutic agent, a targeted therapy, or a combination thereof. In some embodiments of any of the methods provided herein, the chemotherapeutic agent comprises carboplatin, cisplatin, gemcitabine, methotrexate, paclitaxel, pemetrexed, lomustine, temozolomide, dacarbazine, or a combination thereof. In some embodiments of any of the methods provided herein, the targeted therapy comprises afatinib dimaleate, bevacizumab, cetuximab, crizotinib, erlotinib, gefitinib, sorafenib, sunitinib, pazopanib, everolimus, dabrafenib, aldesleukin, interferon alfa-2b, ipilimumab, peginterferon alfa-2b, trametinib, vemurafenib, or a combination thereof. In some embodiments of any of the methods provided herein, the immunomodulator is an immune checkpoint inhibitor selected from the group consisting of: ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, and a combination thereof. In some embodiments of any of the methods provided herein, the immunomodulator is a co- stimulatory immune checkpoint agent selected from the group consisting of: IBI101, utomilumab, MEDI1873, and a combination thereof.

[0034] Also provided herein are methods for treating a subject in need thereof that include administering to the subject a composition comprising an effective amount of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis. [0035] Also provided herein are methods for increasing the response to an immunomodulator in a subject in need thereof that includes administering to the subject a composition comprising an effective amount of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, or twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis . [0036] In some embodiments of any of the methods provided herein, the subject has cancer.

[0037] Also provided herein are methods for treating cancer in a subject that include administering to the subject a composition comprising an effective amount of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis . [0038] Also provided herein are methods for treating cancer in a subject that include (a) detecting a dysbiosis associated with response to therapy with an immunomodulator in a sample from the subject; and (b) administering to the subject a composition comprising an effective amount of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis . [0039] In some embodiments of any of the methods provided herein, the sample is a fecal sample. In some embodiments of any of the methods provided herein, the sample is a tumor biopsy sample.

[0040] In some embodiments of any of the methods provided herein, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining bacterial gene expression in the sample from the subject. In some embodiments of any of the methods provided herein, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining bacterial composition in the sample from the subject. In some embodiments of any of the methods provided herein, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis is increased in the sample from subject.

[0041] In some embodiments of any of the methods provided herein, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that one or more (e.g. two or more, or three) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., and Streptococcus parasanguinis is increased in the sample from subject.

[0042] In some embodiments of any of the methods provided herein, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that one or more (e.g. two or more, or three) bacterial species selected from the group consisting of: Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis is increased in the sample from subject.

[0043] In some embodiments of any of the methods provided herein, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis , are depleted in the sample from subject. [0044] In some embodiments of any of the methods provided herein, one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp. , Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis, are depleted in the gastrointestinal tract of the subject.

[0045] In some embodiments of any of the methods provided herein, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that one or more (e.g. two or more, three or more, or four) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , and Oscillibacter sp. are depleted in the sample from subject. [0046] In some embodiments of any of the methods provided herein, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight) bacterial species selected from the group consisting of: Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis , are depleted in the sample from subject.

[0047] Also provided herein are methods for treating a subject in need thereof that include decreasing a population of an increased bacterial strain in the subject, wherein the increased bacterial strain is one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis .

[0048] In some embodiments of any of the methods provided herein, the subject has cancer. [0049] In some embodiments of any of the methods provided herein, decreasing the population of an increased (e.g., enriched) bacterial strain comprises administering to the subject a bacteriophage. In some embodiments of any of the methods provided herein, decreasing the population of an increased (e.g., enriched) bacterial strain comprises administering to the subject a composition comprising an effective amount of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight) bacterial species selected from the group consisting of: Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitziiBarnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis. [0050] In some embodiments of any of the methods provided herein, the subject is undergoing therapy with an immunomodulator.

[0051] Also provided herein are methods for treating cancer in a subject that include administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of: one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis , wherein the subject is undergoing therapy with an immunomodulator.

[0052] In some embodiments of any of the methods provided herein, the immunomodulator targets one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, or thirteen) of: CTLA-4, PD-1, PD-L1, BTLA, LAG-3, A2AR, TIM- 3, B7-H3, VISTA, IDO, 0X40, 4-1BB, and GITR.

[0053] In some embodiments of any of the methods provided herein, the subject has a solid tumor. In some embodiments of any of the methods provided herein, the subject has a solid tumor selected from the group consisting of: melanoma, lung cancer, kidney cancer, bladder cancer, a head and neck cancer, Merkel cell carcinoma, urothelial cancer, breast cancer, glioblastoma, gastric cancer, a nasopharyngeal neoplasm, colorectal cancer, hepatocellular carcinoma, ovarian cancer, and pancreatic cancer. In some embodiments of any of the methods provided herein, the subject has a hematological malignancy. In some embodiments of any of the methods provided herein, the subject has a hematological malignancy selected from the group consisting of: multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In some embodiments of any of the methods provided herein, the subject has a cancer selected from one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more, eighteen or more, nineteen or more, twenty or more, or twenty-one) of: melanoma, non-small cell lung cancer (NSCLC), small cell lung cancer, squamous cell lung carcinoma, kidney cancer, bladder cancer, a head and neck cancer, Hodgkin lymphoma, Merkel cell carcinoma, urothelial cancer, breast cancer, glioblastoma, gastric adenocarcinoma, transitional cell carcinoma, a biliary tract neoplasm, a nasopharyngeal neoplasm, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and pancreatic cancer. In some embodiments of any of the methods provided herein, the melanoma is unresectable or metastatic melanoma. [0054] In some embodiments of any of the methods provided herein, the bacterial species from the taxonomic genus Bacteroides comprises Bacteroides sp., Bacteroides stercoris, Bacteroides thetaiotaomicron , and Bacteroides vulgatus.

[0055] In some embodiments of any of the methods provided herein, the bacterial species Bacteroides sp. comprises the bacterial strain Bacteroides sp. 14(A). In some embodiments of any of the methods provided herein, the bacterial species Bacteroides stercoris comprises the bacterial strain Bacteroides stercoris A. In some embodiments of any of the methods provided herein, the bacterial species Bacteroides thetaiotaomicron comprises the bacterial strain Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, or a combination thereof. In some embodiments of any of the methods provided herein, the bacterial species Bacteroides vulgatus comprises the bacterial strain Bacteroides vulgatus 3975 RP4. In some embodiments of any of the methods provided herein, the bacterial species Clostridium clostridioforme comprises the bacterial strain Clostridium clostridioforme 90A7. In some embodiments of any of the methods provided herein, the bacterial species Prevotella sp. comprises the bacterial strain Prevotella sp. 109. In some embodiments of any of the methods provided herein, the bacterial species Ruminococcaceae bacterium comprises the bacterial strain Ruminococcaceae bacterium GD6. In some embodiments of any of the methods provided herein, the bacterial species Streptococcus parasanguinis comprises the bacterial strain Streptococcus parasanguinis R-4285. In some embodiments of any of the methods provided herein, the bacterial species Bifidobacterium comprises the bacterial strain Bifidobacterium sp. 12 1 47BFAA, Bifidobacterium adolescentis 221, or a combination thereof. In some embodiments of any of the methods provided herein, the bacterial species Collinsella sp. comprises the bacterial strain Collinsella sp. 4 8 47FAA. In some embodiments of any of the methods provided herein, the bacterial species Methanobrevibacter smithii comprises the bacterial strain Methanobrevibacter smithii TS96C. In some embodiments of any of the methods provided herein, the bacterial species Oscillibacter sp. comprises the bacterial strain Oscillibacter sp. ER4. In some embodiments of any of the methods provided herein, the bacterial species Barnesiella intestinihominis comprises the bacterial strain Barnesiella intestinihominis DSM 21032. In some embodiments of any of the methods provided herein, the bacterial species Ruminococcaceae bacterium comprises the bacterial strain Ruminococcaceae bacterium AFIO 16, Ruminococcaceae bacterium TF06 43, or a combination thereof. In some embodiments of any of the methods provided herein, the bacterial species Intestinimonas timonensis comprises the bacterial strain Intestinimonas timonensis GD4. In some embodiments of any of the methods provided herein, the bacterial species Faecalibacterium prausnitzii comprises the bacterial strain Faecalibacterium prausnitzii CNCM I 4546, Faecalibacterium prausnitzii AM33 14 AC, or a combination thereof. In some embodiments of any of the methods provided herein, the bacterial species Bacteroides caccae comprises the bacterial strain Bacteroides caccae AMI 649B. In some embodiments of any of the methods provided herein, the bacterial species Barnesiella intestinihominis comprises the bacterial strain Barnesiella intestinihominis DSM 21032. In some embodiments of any of the methods provided herein, the bacterial species Faecalibacterium prausnitzii comprises the bacterial strain Faecalibacterium prausnitzii CNCM I 4546. In some embodiments of any of the methods provided herein, the bacterial species Clostridiaceae bacterium comprises the bacterial strain Clostridiaceae bacterium OM08 6BH. In some embodiments of any of the methods provided herein, the bacterial species Clostridium sp. comprises the bacterial strain Clostridium sp. AM33 3.

[0056] In some embodiments of any of the methods provided herein, the bacterial strain improves intestinal barrier function of the subject.

[0057] In some embodiments of any of the methods provided herein, the bacterial strain modulates immune cell function in the subject.

[0058] In some embodiments of any of the methods provided herein, the Bifidobacterium sp. 12 1 47BFAA has a 16S RNA gene that is at least 95% identical to SEQ ID NO:l. In some embodiments of any of the methods provided herein, the Bifidobacterium sp. 12 1 47BFAA has a 16S RNA gene that is at least 95% identical to SEQ ID NO:2. In some embodiments of any of the methods provided herein, t Bifidobacterium sp. 12 1 47BFAA has a 16S RNA gene that is at least 95% identical to SEQ ID NO:3. In some embodiments of any of the methods provided herein, the Collinsella sp. 4 847FAA has a 16S RNA gene that is at least 95% identical to SEQ ID NO:4. In some embodiments of any of the methods provided herein, th Q Methanobrevibacter smithii TS96C has a genomic sequence that is at least 95% identical to GCF 000190175. In some embodiments of any of the methods provided herein, the Oscillibacter sp. ER4 has a 16S RNA gene that is at least 95% identical to SEQ ID NO:5.

[0059] In some embodiments of any of the methods provided herein, the bacterial strain in the composition is viable. In some embodiments of any of the methods provided herein, the bacterial strain is lyophilized. [0060] In some embodiments of any of the methods provided herein, the composition further comprises one or more cryopreservants.

[0061] In some embodiments of any of the methods provided herein, the effective amount of the bacterial strain comprises at least about 1 xlO ³ colony forming units (CFU) of the bacterial strain.

[0062] In some embodiments of any of the methods provided herein, the effective amount of the bacterial strain comprises about 1 xlO ⁴ to about 1 xlO ¹⁵ CFU of the bacterial strain. In some embodiments of any of the methods provided herein, the effective amount of the bacterial strain comprises about 1 xlO ⁶ to about 1 xlO ¹⁰ CFU of the bacterial strain. [0063] In some embodiments of any of the methods provided herein, the bacterial strain in the composition is non-viable. In some embodiments of any of the methods provided herein, the non-viable bacterial strain is heat-killed, irradiated, or lysed.

[0064] In some embodiments of any of the methods provided herein, the method comprises administering the composition to the subject once, twice, or three times per day. [0065] In some embodiments of any of the methods provided herein, the composition is formulated for oral administration. In some embodiments of any of the methods provided herein, the composition is formulated as a tablet, a capsule, a powder, or a liquid. In some embodiments of any of the methods provided herein, the composition is formulated as a tablet. In some embodiments of any of the methods provided herein, the tablet is coated. In some embodiments of any of the methods provided herein, the coating comprises an enteric coating.

[0066] In some embodiments of any of the methods provided herein, the composition is formulated for rectal administration. In some embodiments of any of the methods provided herein, the composition is formulated for intravenous administration. In some embodiments of any of the methods provided herein, the composition is formulated for intratumoral administration.

[0067] In some embodiments of any of the methods provided herein, the method further comprises administering another treatment of cancer and/or other adjunct therapy to the subject. In some embodiments of any of the methods provided herein, the composition comprising the bacterial strain treatment and the treatment for cancer and/or adjunct therapy are administered simultaneously. In some embodiments of any of the methods provided herein, the composition comprising the bacterial strain treatment and the treatment for cancer and/or adjunct therapy are administered sequentially.

[0068] In some embodiments of any of the methods provided herein, the treatment for cancer and/or adjunct therapy comprises a probiotic.

[0069] In some embodiments of any of the methods provided herein, the treatment for cancer and/or adjunct therapy comprises surgery, radiation therapy, or a combination thereof.

[0070] In some embodiments of any of the methods provided herein, the treatment for cancer and/or adjunct therapy comprises a therapeutic agent. In some embodiments of any of the methods provided herein, the therapeutic agent comprises a chemotherapeutic agent, a targeted therapy, an immunotherapy, or a combination thereof. In some embodiments of any of the methods provided herein, the chemotherapeutic agent comprises carboplatin, cisplatin, gemcitabine, methotrexate, paclitaxel, pemetrexed, lomustine, temozolomide, dacarbazine, or a combination thereof. In some embodiments of any of the methods provided herein, the targeted therapy comprises afatinib dimaleate, bevacizumab, cetuximab, crizotinib, erlotinib, gefitinib, sorafenib, sunitinib, pazopanib, everolimus, dabrafenib, aldesleukin, interferon alfa-2b, ipilimumab, peginterferon alfa-2b, trametinib, vemurafenib, or a combination thereof. In some embodiments of any of the methods provided herein, the immunotherapy comprises a cell therapy, a therapy with an immunomodulator, or a combination thereof.

[0071] In some embodiments of any of the methods provided herein, the immunomodulator is an immune checkpoint inhibitor selected from the group consisting of: ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, and a combination thereof. In some embodiments of any of the methods provided herein, the immunomodulator is a co-stimulatory immune checkpoint agent selected from the group consisting of: IBIIOI, utomilumab, MEDI1873, and a combination thereof.

[0072] In some embodiments of any of the methods provided herein, the composition comprising the bacterial strain further comprises the therapeutic agent. [0073] In some embodiments of any of the methods provided herein, the cell therapy is a CAR T-cell therapy

[0074] In some embodiments of any of the methods provided herein, the subject is a human.

[0075]

[0076] Provided herein are methods and compositions for treating a subj ect in need thereof. For example, methods provided herein can include administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof. In some embodiments, the subject has cancer (e.g., melanoma, non-small cell lung cancer (NSCLC), kidney cancer, bladder cancer, a head and neck cancer, Hodgkin’s lymphoma, non-Hodgin’s lymphoma, Merkel cell carcinoma, urothelial cancer, breast cancer, glioblastoma, or pancreatic cancer). In some embodiments, the melanoma can be unresectable or metastatic melanoma. In some embodiments, the subject is undergoing therapy with an immunomodulator (e.g., with an immune checkpoint inhibitor that targets one or more of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), PD-1 (Programmed cell death protein 1), PD-L1 (Programmed death-ligand 1), BTLA (B and T lymphocyte attenuator), LAG-3 (Lymphocyte Activation Gene 3), A2AR (Adenosine A2a receptor), TIM-3 (T-cell immunoglobulin and mucin domain-3), B7-H3 (B7 homolog 3; also known as CD276), VISTA (V-domain Ig suppressor of T cell activation), and IDO (indoleamine 2,3-dioxygenase) and/or with a co-stimulatory agent that targets one or more of 0X40 (Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)), 4-1BB (tumor necrosis factor receptor superfamily member 9 (TNFRSF9)), and GITR (glucocorticoid-induced TNFR-related protein). In some embodiments, the subject is not responding to therapy with an immunomodulator.

[0077] Also, provided herein are methods for treating cancer in a subject that include administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof. Also, provided herein are methods for increasing the response to a therapy with an immunomodulatory in a subject in need thereof that includes administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof. [0078] Also provided herein are methods for treating cancer in a subject that include (a) detecting a dysbiosis associated with response to therapy with an immunomodulator (e.g., an immune checkpoint inhibitor therapy or a co-stimulatory immune checkpoint therapy) in a sample (e.g., a biopsy sample such as a tumor biopsy sample, or a fecal sample) from the subject; and (b) administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof.

[0079] In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulatory (e.g., an immune checkpoint inhibitor therapy and/or a co stimulatory immune checkpoint therapy) comprises determining bacterial gene expression in the sample from the subject. In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining bacterial composition in the sample from the subject. In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that Bacteroides sp. 14(A), Bacteroides stercoris A, Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, Bacteroides vulgatus 3975 RP4, Clostridium clostridioforme 90 A7, Prevotella sp. 109, Ruminococcaceae bacterium GD6, Streptococcus parasanguinis R-4285, or a combination thereof, is increased (e.g., enriched) in the sample from subject. In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that Bacteroides sp. 14(A), Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, Bacteroides vulgatus 3975 RP4, Clostridium clostridioforme 90A7, Prevotella sp. 109, Ruminococcaceae bacterium GD6, Streptococcus parasanguinis R-4285, or a combination thereof, is increased (e.g., enriched) in the sample from subject. In some embodiments, the subject is not responding to therapy with an immunomodulator. In some embodiments, the dysbiosis associated with response to therapy with an immunomodulator decreases the efficacy of the therapy with an immunomodulator.

[0080] In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, or a combination thereof, is decreased (e.g., reduced) in the sample from subject (e.g., in the gastrointestinal tract of the subject).

[0081] Also provided herein are methods for treating a subject in need thereof (e.g., the subject has cancer and/or is undergoing therapy with an immunomodulator). The method can include decreasing a population of an increased (e.g., enriched) bacterial strain in the subject, wherein the increased (e.g., enriched) bacterial strain is selected from the group consisting of: Bacteroides sp. 14(A), Bacteroides stercoris A, Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, Bacteroides vulgatus 3975 RP4, Clostridium clostridioforme 90 A7, Prevotella sp. 109, Ruminococcaceae bacterium GD6, Streptococcus parasanguinis R-4285, and a combination thereof. In some embodiments, the increased (e.g., enriched) bacterial strain is selected from the group consisting of: Bacteroides sp. 14(A), Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, Bacteroides vulgatus 3975 RP4, Clostridium clostridioforme 90 A7, Prevotella sp. 109, Ruminococcaceae bacterium GD6, Streptococcus parasanguinis

R-4285, and a combination thereof. In some embodiments, decreasing the population of an increased (e.g., enriched) bacterial strain can include administering to the subject a bacteriophage. In some embodiments, decreasing the population of an increased (e.g., enriched) bacterial strain can include administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof.

[0082] In some embodiments, the bacterial strain comprises Bifidobacterium sp. 12 1 47BFA. In some embodiments, the bacterial strain comprises Collinsella sp. 4 8 47FAA. In some embodiments, the bacterial strain comprises Methanobrevibacter smithii TS96C. In some embodiments, the bacterial strain comprises Oscillibacter sp. ER4.

[0083] In some embodiments, the bacterial strain improves intestinal barrier function of the subject.

[0084] In some embodiments, strain Bifidobacterium sp. 12 1 47BFA has a 16S RNA gene that is at least 90%, 94%, 95%, or 99% identical to one or more (e.g., one, two, or all) of SEQ ID NO:l, SEQ ID NO:2, and SEQ ID NO:3. In some embodiments, strain Collinsella sp. 4 8 47FAA has a 16S RNA gene that is at least 90%, 94%, 95%, or 99% identical to SEQ ID NO:4. In some embodiments, strain Methanobrevibacter smithii TS96C has a genomic sequence that is at least 90%, 94%, 95%, or 99% identical to GCF_000190175. In some embodiments, strain Oscillibacter sp. ER4 has a 16S RNA gene that is at least 90%, 94%, 95%, or 99% identical to SEQ ID NO: 5.

[0085] In some embodiments, the bacterial strain in the composition is viable. In some embodiments, the bacterial strain is lyophilized. In some embodiments, the composition further comprises one or more cryopreservants.

[0086] In some embodiments, the effective amount of the bacterial strain comprises at least about 1 xlO ³ colony forming units (CFU) of the bacterial strain. In some embodiments, the effective amount of the bacterial strain comprises about 1 xlO ⁴ to about 1 xlO ¹⁵ CFU of the bacterial strain. In some embodiments, the effective amount of the bacterial strain comprises about 1 xlO ⁶ to about 1 xlO ¹⁰ CFU of the bacterial strain.

[0087] In some embodiments, the bacterial strain in the composition is non-viable. In some embodiments, the non-viable bacterial strain is heat-killed, irradiated, or lysed.

[0088] In some embodiments, the method comprises administering the composition to the subject once, twice, or three times per day.

[0089] In some embodiments, the composition further includes one or more excipients. In some embodiments, the composition is formulated for oral administration. In some embodiments, the composition is formulated for rectal administration. In some embodiments, the composition is formulated for intravenous administration. In some embodiments, the composition is formulated for intratumoral administration. In some embodiments, the composition is formulated as a tablet, a capsule, a powder, or a liquid. In some embodiments, the composition is formulated as a tablet. In some embodiments, the tablet is coated. In some embodiments, the coating comprises an enteric coating. [0090] In some embodiments, methods described herein comprise administering a composition comprising a bacterial strain as described herein in combination with one or more treatments of cancer and/or other adjunct therapies to the subject. In some embodiments, the treatment of cancer and/or other adjunct therapy can be a therapeutic agent such as a chemotherapeutic agent, a targeted therapy, or a combination thereof. In some embodiments, the chemotherapeutic agent is carboplatin, cisplatin, gemcitabine, methotrexate, paclitaxel, pemetrexed, lomustine, temozolomide, dacarbazine, or a combination thereof. In some embodiments, the target therapy is afatinib dimaleate, bevacizumab, cetuximab, crizotinib, erlotinib, gefitinib, sorafenib, sunitinib, pazopanib, everolimus, dabrafenib, aldesleukin, interferon alfa-2b, ipilimumab, peginterferon alfa-2b, trametinib, vemurafenib, or a combination thereof.

[0091] In some embodiments, the treatment of cancer and/or other adjunct therapy is surgery and/or radiation therapy. In some embodiments, the treatment of cancer and/or other adjunct therapy comprises a probiotic.

[0092] In some embodiments, the composition comprising the bacterial strain and the one or more treatments of cancer and/or adjunct therapies are administered simultaneously (e.g., in the same composition or different compositions). In some embodiments, the composition comprising the bacterial strain and the one or more treatments of cancer and/or other adjunct therapies are administered sequentially.

[0093] In any of the methods, the subject can be a human.

[0094] As used herein, the phrase an "effective amount" of a bacterial strain can refer to an amount of the bacterial strain sufficient enough to reduce or eliminate one or more symptoms of the disorder or in some cases, to effect a cure upon administration. Effective amounts of a bacterial strain will vary with the bacterial strain chosen, the particular condition or conditions being treated, the severity of the condition, the duration of the treatment, the specific components of the composition being used, and like factors. An "effective amount" can also refer to an amount of a combination of two or more bacterial strains or a combination of a bacterial strain and a therapeutic agent sufficient to reduce or eliminate one or more symptoms of the disorder or in some cases, to effect a cure upon administration. For example, an "effective amount" can refer to an amount of a combination of bacterial strains or a combination of a bacterial strain and another treatment (e.g., a therapeutic agent) when an additive or synergistic effect is observed with the combination compared to administration of the bacterial strain(s) and/or therapeutic agent(s) alone.

[0095] As used herein, "subject" or "patient" refers to any subject, particularly a mammalian subject such as a human, for whom diagnosis, prognosis, or therapy is desired. [0096] As used herein, "treatment" or "treating" of a disease, disorder, or condition encompasses alleviation of at least one symptom thereof, a reduction in the severity thereof, or the delay or inhibition of the progression thereof. Treatment need not mean that the disease, disorder, or condition is totally cured. A useful composition herein needs only to reduce the severity of a disease, disorder, or condition, reduce the severity of one or more symptoms associated therewith, or improve a patient or subject's quality of life.

[0097] The term "preventing" as used herein means the prevention of the onset, recurrence, or spread, in whole or in part, of the disease or condition as described herein, or a symptom thereof.

[0098] The term “administration” or “administering” refers to a method of giving an amount of a bacterial strain, or a composition thereof, or other treatment of cancer and/or adjunct therapy to a subject. The method of administration can vary depending on various factors, e.g., the components of the composition, the site of the disease, and the severity of the disease.

[0099] “Microbiome” refers to the collection of microorganisms and viruses and/or their genes from a given environment. For example, “microbiome” can refer to the collection of the microorganisms and viruses and/or their genes from the gastrointestinal tract of humans. “Microbiota” refers to the microorganisms in a specific environment.

[00100] “Dysbiosis” refers to a state of the microbiota or microbiome of the gut or other body area (e.g., mucosal or skin surfaces or any other microbiota niche) of a subject (i.e., the host) in which the diversity and/or function of the ecological network is disrupted, e.g., as compared to the state of the microbiota or microbiome of the gut or other body area in a control population (e.g., a reference population). A control population can include individuals that meet one or more qualifications such as individuals that have not been diagnosed with a disease (e.g., the same disease as the subject); individuals that do not have a known genetic predisposition to a disease (e.g., the same disease as the subject); or individuals that do not have a known environmental predisposition to a disease (e.g., the same disease as the subject); or individuals that do not have a known predisposition that would prevent treatment of and/or recovery from a disease (e.g., the same disease as the subject). In some embodiments, the individuals in the control population meet one of the above control population qualifications. In some embodiments, the individuals in the control population meet two of the above control population qualifications. In some embodiments, the individuals in the control population meet three of the above control population qualifications. In some embodiments, the individuals in the control population meet four of the above control population qualifications. In some embodiments, the control population is homogenous with respect to at least one of the qualifications. Any disruption in the microbiota or microbiome of a subject (i.e., host) compared to the microbiota or microbiome of a control population can be considered a dysbiosis, even if such dysbiosis does not result in a detectable decrease in health of the subject. Dysbiosis in a subject may be unhealthy for the subject (e.g., result in a diseased state in the subject), it may be unhealthy for the subject under only certain conditions (e.g., result in diseased state under only certain conditions), or it may prevent the subject from becoming healthier (e.g., may prevent a subject from responding to treatment or recovering from a disease or disorder). Dysbiosis may be due to a decrease in diversity of the microbiota population composition (e.g., a depletion of one or more bacterial strains, an overgrowth of one or more bacterial strains, or a combination thereof), the overgrowth of one or more population of pathogens (e.g., a population of pathogenic bacteria) or pathobionts, the presence of and/or overgrowth of a symbiotic organism able to cause disease only when certain genetic and/or environmental conditions are present in a subject, or a shift to an ecological network that no longer provides a beneficial function to the host and therefore no longer promotes health. [00101] As used herein the terms “microorganism” or “microbe” should be taken broadly. These terms are used interchangeably and include, but are not limited to, the two prokaryotic domains, Bacteria and Archaea, as well as eukaryotic fungi and protists. In some embodiments, the disclosure refers to a “bacterium” or a “microbe.” This characterization can refer to not only the identified taxonomic bacterial genera of the microbe, but also the identified taxonomic species, as well as the bacterial strains. A “strain” can include descendants of a single isolation in pure culture that is usually made up of a succession of cultures ultimately derived from an initial single colony. In some embodiments, a strain includes an isolate or a group of isolates that can be distinguished from other isolates of the same genus and species by phenotypic characteristics, genotypic characteristics, or both.

[00102] The term “relative abundance” as used herein, is the number or percentage of a microbe present in the gastrointestinal tract or any other microbiota niche of a subject, such as the ocular, placental, lung, cutaneous, urogenital, or oral microbiota niches, relative to the number or percentage of total microbes present in the gastrointestinal tract or the other microbiota niche of the subject. The relative abundance may also be determined for particular types of microbes such as bacteria, fungi, viruses, and/or protozoa, relative to the total number or percentage of bacteria, fungi, viruses, and/or protozoa present. Relative abundance can be determined by a number of methods readily known to the ordinarily skilled artisan, including, but not limited to, array or microarray hybridization, sequencing, quantitative PCR, and culturing and performance of colony forming unit (cfu, CFU) assays or plaque forming unit (pfu, PFU) assays performed on a sample from the gastrointestinal tract or other microbiota niche.

[00103] As used herein, terms such as “isolate” and “isolated” in reference to a microbe, are intended to mean that a microbe has been separated from at least one of the materials with which it is associated in a particular environment (for example gastrointestinal fluid, gastrointestinal tissue, human digestive fluid, human digestive tissue, etc.). Accordingly, an “isolated microbe” does not exist in its naturally occurring environment. In some embodiments, an isolated microbe, e.g., a bacterial strain, may exist as, for example, a biologically pure culture, or as spores (or other forms of the bacterial strain) in association with a pharmaceutically acceptable excipient suitable for human administration. In some embodiments, more than one microbe can be isolated. For example, “isolated microbes” can refer to a mixture of two or more microbes that have been separated from at least one of the materials with which they are associated in a particular environment.

[00104] In some embodiments, the isolated microbes exist as isolated and biologically pure cultures. As used herein, the term “biologically pure” refers to a composition comprising a species or strains of a microbe, wherein the composition is substantially free from the material from which the microbe was isolated or produced and from other microbes (e.g., other species or strains and other microbes of a different taxonomic classification). In some embodiments, “biologically pure” can refer to a composition that comprises a strain of a bacterial strain that is substantially free from the material from which the bacterial strain was isolated or produced and from other microbes, e.g., other strains of the same bacterial strain, other species of the same bacteria, and other bacteria and/or microbes of a different taxonomic classification). It will be appreciated by one of skill in the art, that an isolated and biologically pure culture of a particular microbe, denotes that said culture is substantially free (within scientific reason) of other living organisms and contains only the individual microbe in question. As used herein, “substantially free” means that a composition comprising a species or strain of a microbe is at least about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% free of the material from which the microbe was isolated or produced and from other microbes. In some embodiments, a biologically pure composition contains no other bacterial strain in quantities that can be detected by typical bacteriological techniques. [00105] As used herein, the term “mutation” includes a natural or induced mutation comprising at least a single base or amino acid alteration in a DNA or protein sequence. For example, a mutation can include a base substitution, a deletion, an insertion, a transversion, or any other modification known to those skilled in the art, including a genetic modification introduced into a parent nucleotide or an amino acid sequence. [00106] As used herein, “probiotic” refers to a substantially pure microbe (i.e., a single isolate) or a mixture of microbes, and may also include any additional components that can be administered to a subject (e.g., a human), for restoring or altering the microbiota or microbiome in the subject. In some embodiments, a probiotic or microbial inoculant composition can be administered with an agent to allow the microbe(s) to survive the environment of the gastrointestinal tract, i.e., to resist low pH and/or to grow in the gastrointestinal environment. In some embodiments, a composition as described herein includes a probiotic.

[00107] As used herein, “prebiotic” refers to an agent that increases the number and/or activity of one or more microbes. Such microbes can include microbes for restoring or altering the microbiota or microbiome of a subject. Non-limiting examples of a prebiotic include a fructooligosaccharide (e.g., oligofructose, inulin, or an inulin-type fructan), a galactooligosaccharide, an amino acid, an alcohol. See, for example, Rami rez-F arias et al. (2008. Br. JNutr. 4:1-10) and Pool-Zobel and Sauer (2007. JNutr. 137:2580-2584). [00108] As used herein, a “live biotherapeutic product” or “LBP” refers to a biological product that: 1) contains live organisms, such as bacteria, and 2) is applicable to the prevention, treatment, and/or cure of a disease or condition of a subject.

[00109] A “combination” of two or more bacteria, e.g., bacterial strains, can refer to the physical co-existence of the bacteria, either in the same material or product. In some embodiments, a combination of two or more bacteria can include the temporal co administration or co-localization of the two or more bacteria.

[00110] The terms “percent identity” or “identity” in the context of two or more nucleic acids or polypeptides, refers to the measurement of the similarity between the two or more sequences. The percent identity can be measured by any method known to one of skill in the art including using a sequence comparison software, an algorithm, and by visual inspection.

[00111] In general, the percent identity for two or more sequences (e.g., a nucleic acid or amino acid sequence), also referred to as the “percent sequence identity”, is calculated by determining the number of matched positions in the aligned nucleic acid or amino acid sequences, dividing the number of matched positions by the total number of aligned nucleotides or amino acids, respectively, and multiplying by 100. A matched position refers to a position in which identical nucleotides or amino acids occur at the same position in the aligned sequences. As an example, the total number of aligned nucleotides can refer to the minimum number of the 16S rRNA gene nucleotides that are necessary to align the second sequence, and does not include alignment (e.g., forced alignment) with non-16S rRNA gene sequences. The total number of aligned nucleotides may correspond to the entire 16S rRNA gene sequence or may correspond to fragments of the full-length 16S rRNA gene sequence.

[00112] Sequences can be aligned using an algorithm, for example, the algorithm as described by Altschul et al. (Nucleic Acids Res, 25:3389-3402, 1997) and incorporated into BLAST (basic local alignment search tool) programs, which are available at ncbi.nlm.nih.gov. BLAST searches or alignments can be performed to determine percent sequence identity between a 16S rRNA gene nucleic acid and any other sequence or portion thereof using the Altschul et al. algorithm. BLASTN can be used to align and compare the identity between nucleic acid sequences, while BLASTP can be used to align and compare the identity between amino acid sequences. When utilizing a BLAST program to calculate the percent identity between a 16S rRNA gene sequence and another sequence, the default parameters of the program are used.

[00113] Generally, a bacterial strain genomic sequence will contain multiple copies of 16S rRNA sequences. The 16S rRNA sequences can be used for making distinctions between species and strains. For example, if one or more of the 16S rRNA sequences shares less than 97% sequence identity from a reference sequence, then the two organisms from which the sequences were obtained can be of different species or strains.

[00114] The term "combination therapy" as used herein refers to a dosing regimen of one or more bacterial strains and one or more other treatments of cancer and/or adjunct therapies, wherein the bacterial strain and other treatment (e.g., a therapeutic agent) are administered together or separately in a manner prescribed by a medical care taker or according to a regulatory agency. As can be appreciated in the art, a combination therapy can be administered to a patient for a period of time. In some embodiments, the period of time occurs following the administration of one or more of: a different bacterial strain, a different treatment/therapeutic agent, and a different combination of treatments/therapeutic agents to the subject. In some embodiments, the period of time occurs before the administration of one or more of: a different bacterial strain, a different treatment/therapeutic agent, and a different combination of therapeutic treatments/agents to the subject.

[00115] The term "fixed combination" means that one or more bacterial strains as described herein, or a composition thereof, and at least one other treatment and/or adjunct therapy (e.g., a prebiotic, a probiotic, a chemotherapeutic agent, a targeted therapy, or a combination thereof), are both administered to a subject simultaneously in the form of a single composition or dosage.

[00116] The term "non-fixed combination" means that one or more bacterial strains as described herein, or a composition thereof, and at least one other treatment or adjunct therapy (a prebiotic, a probiotic, a chemotherapeutic agent, a targeted therapy, or a combination thereof) are formulated as separate compositions or dosages such that they may be administered to a subject simultaneously or sequentially with variable intervening time limits. These also apply to cocktail therapies, e.g., the administration of three or more therapeutic agents.

[00117] Reference to the term "about" has its usual meaning in the context of compositions to allow for reasonable variations in amounts that can achieve the same effect and also refers herein to a value of plus or minus 10% of the provided value. For example, "about 20" means or includes amounts from 18 to and including 22.

[00118] Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. As used herein, the singular form "a", "an", and "the" include plural references unless indicated otherwise. For example, "an" excipient includes one or more excipients. It is understood that aspects and variations of the invention described herein include "consisting of’ and/or "consisting essentially of’ aspects and variations.

[00119] The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.

[00120] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.

DESCRIPTION OF DRAWINGS [00121] FIG. 1 is an exemplary schematic of the analysis.

[00122] FIG. 2 has plots showing the tallies of strains detected (after prevalence filtering). The top panel tallies the strains detected in increasing number of datasets. The middle panel shows the number of strains that were significantly differentially abundant in 1 or more datasets. The bottom panel shows the number of strains that exhibit concordance in direction of the log 2 fold change, in increasing proportions of datasets in which they were detected. Only strains detected in at least two datasets are included.

[00123] FIG. 3 is a plot showing the distribution of effect sizes per dataset. 16S-NGS refers to sequencing of the 16S rRNA gene via next generation sequencing (NGS). WGS- NGS refers to whole genome shotgun (WGS) sequencing on a NGS platform.

[00124] FIG. 4 is a plot showing strains (dots) significantly differentially abundant in eubiotic or dysbiotic state by isolated-dataset analysis (grey squares) or MTMA (grey spheres) in melanoma. Strains (dots) are sized by the number of datasets in which they were detected and colored as follows: significant by isolated analysis only (dark green); MTMA only (purple); or both (blue). Solid lines connect MTMA results to strains and dashed lines connect isolated analysis results to strains. Thick and thin lines indicate significant and non-significant findings, respectively. Red and green lines indicate enrichment and reduction in dysbiotic state, respectively. Annotation for strains described here are provided in FIG. 8.

[00125] FIG. 5 is a forest plot demonstrating distribution of log 2 fold changes and 95% confidence intervals for strains that were identified as significantly differentially abundant by MTMA. Circles and triangles indicate log 2 fold change estimated by isolated analysis and MTMA, respectively. Error bars in the forest plots correspond to the 95% confidence interval. Green and blue indicate significant and nonsignificant findings, respectively, and grey indicates cases where an adjusted p-value could not be imputed by the statistical test. [00126] FIG. 6 is a plot of MTMA-derived adjusted p-values and log 2 fold changes.

Data points are shaded according to the proportion of datasets in which the strain was detected. Significantly dysbiosis-associated strains plot in the upper left quadrant, whereas homeostasis-associated strains plot in the upper right quadrant. FIG. 8 provides strain names for strain identifiers indicated in the plot. [00127] FIG. 7 is a table showing details on contrasts analyzed within each cohort of subjects.

[00128] FIG. 8 is a table showing the association between the strain identifiers and strain names.

[00129] FIG. 9 is a schematic of the study design. [00130] FIG. 10 is a plot of Uniform Manifold Approximation and Projection

(UMAP) projection of the functional and taxonomic profiles of the meta-cohort microbiomes

[00131] FIG. 11 is a plot showing model classification metrics.

[00132] FIG. 12 is a plot that shows exclusion of partial responders from the training set further improved results.

[00133] FIG. 13 is a plot showing refinement of the lead model.

[00134] FIG. 14 is a plot showing the UMAP projection of the composite biomarker features for the meta-cohort.

[00135] FIG. 15 is a plot showing the ROC curve on validation set. [00136] FIG. 16 is a expression heatmap of the 20 features. [00137] FIG. 17 is a plot showing feature effect size.

DETAILED DESCRIPTION

[00138] This document provides compositions and methods for treating subjects in need thereof (e.g., subjects having cancer or being treated with one or more immunomodulators) using one or more bacterial strains. An immunomodulator can include an immune checkpoint inhibitor and/or a co-stimulatory immune checkpoint agent. Non limiting examples of immune checkpoint inhibitors include inhibitors that target CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) such as ipilimumab (YERVOY®); PD-1 (Programmed cell death protein 1) such as pembrolizumab (KEYTRUDA®), nivolumab (OPDIVO®), or cemiplimab (LIBTAYO®); PD-L1 (Programmed death-ligand 1) such as atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®), or durvalumab (IMFINZI®); BTLA (B and T lymphocyte attenuator); LAG-3 (Lymphocyte Activation Gene 3) such as IMP701 (LAG525); A2AR (Adenosine A2a receptor) such as CPI-444; TIM-3 (T-cell immunoglobulin and mucin domain-3) such as MBG453; B7-H3 (B7 homolog 3; also known as CD276) such as enoblituzumab; VISTA (V-domain Ig suppressor of T cell activation) such as JNJ-61610588; and IDO (Indole amine 2,3 -di oxygenase) such as indoximod. See, for example, Marin-Acevedo, et ah, JHematol Oncol. 11: 39 (2018). Non limiting examples of co-stimulatory immune checkpoint agents include agents that target 0X40 such as IBIIOI; 4-1BB such as utomilumab (PF-05082566); and GITR such as MEDI1873.

[00139] While immunotherapy with immunomodulators such as those described herein has largely been effective, many subjects do not respond to immune checkpoint inhibitors (see, e.g., Humphries and Daud. Hum Vaccin Immunother. 2018; 14(9): 2178- 2182). The gut microbiome may be one of the factors that determines the efficacy of immune checkpoint treatment and whether a subject responds to such treatment.

[00140] In some embodiments, methods for treating a subject in need thereof are provided herein. In some embodiments, one or more of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4 is decreased (e.g., reduced) in a sample (e.g., fecal sample or a biopsy sample such as an intestinal biopsy sample or a colorectal biopsy sample) from the subject in need thereof. For example, one or more of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4 is decreased (e.g., reduced) in the sample (e.g., fecal sample or a biopsy sample such as an intestinal biopsy sample or a colorectal biopsy sample) from the subject in need thereof compared to a control sample. Determining that one or more of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4 is decreased (e.g., reduced) in the sample from the subject in need thereof can comprise sequencing one or more nucleic acids from the bacteria. In some embodiments, methods for increasing the response to therapy with an immunomodulatory (e.g., an immune checkpoint inhibitor therapy and/or a co-stimulatory immune checkpoint therapy) in a subject in need thereof are provided herein. The methods provided herein can include administering to the subject a composition that includes an effective amount of a bacterial strain. In some embodiments, the bacterial strain can be selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof (e.g., any two, any three, or all four of the bacterial strains.

[00141] In some embodiments, the subject in need thereof has been diagnosed with cancer and/or is being treated with one or more immunomodulators (e.g., an immune checkpoint inhibitor therapy and/or a co-stimulatory immune checkpoint therapy). In some embodiments, the cancer is any cancer that can be treated with an immunomodulator such as those described herein. The cancer can be a solid tumor or a hematological malignancy. Non-limiting examples of a solid tumor include: melanoma (e.g., metastatic or non- resectable), lung cancer (e.g., non-small cell lung cancer (NSCLC), small cell lung cancer, extensive stage small cell lung cancer, and squamous cell lung carcinoma), kidney cancer (e.g., renal cell carcinoma and metastatic clear cell renal carcinoma), bladder cancer, a head and neck cancer (e.g., head and neck squamous cell carcinoma), Merkel cell carcinoma, urothelial cancer, breast cancer, glioblastoma, gastric cancer (e.g., gastric adenocarcinoma, and gastric cancer and gastroesophageal junction cancer), a nasopharyngeal neoplasm (e.g., hypopharyngeal squamous cell carcinoma), colorectal cancer, hepatocellular carcinoma, ovarian cancer, and pancreatic cancer. Non-limiting examples of a hematological malignancy include: multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In some embodiments, the subject has a cancer selected from one or more of: melanoma, non-small cell lung cancer (NSCLC), small cell lung cancer, squamous cell lung carcinoma, kidney cancer, bladder cancer, a head and neck cancer, Hodgkin lymphoma, Merkel cell carcinoma, urothelial cancer, breast cancer, glioblastoma, gastric adenocarcinoma, transitional cell carcinoma, a biliary tract neoplasm, a nasopharyngeal neoplasm, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and pancreatic cancer.

[00142] In some embodiments, the bacterial strain Bifidobacterium sp. 12 1 47BFAA. In some embodiments, the bacterial strain in the composition comprises Bifidobacterium sp. 12 1 47BFAA. A complete genomic sequence for Bifidobacterium sp. 12 1 47BFAA is available in the GenBank database as, e.g., Accession No. GCF 000185665. In some embodiments, the Bifidobacterium sp. 12 1 47BFAA included in a composition provided herein can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000185665. For example, Bifidobacterium sp. 12 1 47BFAA included in a composition provided herein can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about

99.9% sequence identity to the genomic sequence published as GCF 000185665. In some embodiments, Bifidobacterium sp. 12 1 47BFAA included in a composition provided herein has a 16S RNA gene that is at least 90% identical to one or more (e.g., one, two, or all) of SEQ ID NO:l, SEQ ID NO:2, and SEQ ID NO:3 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about

95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more (e.g., one, two, or all) of SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3). [00143] In some embodiments, the bacterial strain in the composition comprises Collinsella sp. 4 8 47FAA. A complete genomic sequence for Collinsella sp. 4 8 47FAA is available in the GenBank database as, e.g., Accession No. GCF 000763055. In some embodiments, the Collinsella sp. 4 8 47FAA included in a composition provided herein can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000763055. For example, Collinsella sp. 4 847FAA included in a composition provided herein can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000763055. In some embodiments, Collinsella sp. 4 8 47FAA included in a composition provided herein can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:4 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:4).

[00144] In some embodiments, the bacterial strain in the composition comprises Methanobrevibacter smithii TS96C. A complete genomic sequence for Methanobrevibacter smithii TS96C is available in the GenBank database as, e.g., Accession No. GCF 000190175. In some embodiments, the Methanobrevibacter smithii TS96C included in a composition provided herein can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000190175. For example, Methanobrevibacter smithii TS96C included in a composition provided herein can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000190175.

[00145] In some embodiments, the bacterial strain in the composition comprises Oscillibacter sp. ER4. A complete genomic sequence for Oscillibacter sp. ER4 is available in the GenBank database as, e.g., Accession No. GCF 000765235. In some embodiments, the Oscillibacter sp. ER4 strain included in a composition provided herein can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000765235. For example, Oscillibacter sp. ER4 included in a composition provided herein can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about

99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000765235 In some embodiments, Oscillibacter sp. ER4 included in a composition provided herein has a 16S RNA gene that is at least 90% identical to SEQ ID NO:5 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:5).

[00146] In some embodiments, the composition can include two or more bacterial strains selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4. For example, the composition can include Bifidobacterium sp. 12 1 47BFAA and Collinsella sp. 4 8 47FAA; Bifidobacterium sp. 12 1 47BFAA and Methanobrevibacter smithii TS96C, Bifidobacterium sp. 12 1 47BFAA and Oscillibacter sp. ER4; Collinsella sp. 4 8 47FAA and Methanobrevibacter smithii TS96C; Collinsella sp. 4 8 47FAA and Oscillibacter sp. ER4; Methanobrevibacter smithii TS96C and Oscillibacter sp. ER4; Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, and Methanobrevibacter smithii TS96C; Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, and Oscillibacter sp. ER4; Bifidobacterium sp. 12 1 47BFAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4; Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4; or Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4. Identifying characteristics of each strain are described above.

[00147] In some embodiments, methods are provided for identifying a subject likely to respond to therapy with an immunomodulator (e.g., an immune checkpoint inhibitor therapy and/or a co-stimulatory immune checkpoint therapy). For example, the methods provided herein can include detecting the presence or absence of a bacterial strain (e.g., one or more of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4) or relative amount of the bacterial strain in a biological sample from the subject (e.g., compared to a control population). A subject can be identified as likely to respond to therapy with an immunomodulator when one or more of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4 is increased (e.g., enriched) or not reduced (e.g., not decreased) in the biological sample from the subject. In some embodiments, the subject can be identified as not likely to respond to therapy with an immunomodulator when the bacterial strain (e.g., one or more of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4) is decreased (e.g., reduced) compared to a reference sample (e.g., compared to a control sample). In some embodiments, a subject that is not likely to respond to therapy with an immunomodulator can be administered a composition comprising an effective amount of a bacterial strain (e.g., a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof). [00148] In some embodiments, a method can include detecting, in a sample from the subject, a dysbiosis associated with response to therapy with an immunomodulator, e.g., before administering to the subject an effective amount of a bacterial strain or a composition containing the bacterial strain. In some embodiments, a dysbiosis associated with response to therapy with an immunomodulator is present in the subject before treatment with an immunomodulator. In some embodiments, a dysbiosis associated with response to therapy with an immunomodulator in a subj ect is present during treatment with an immunomodulator. In some embodiments, a dysbiosis associated with response to therapy with an immunomodulator decreases the efficacy of the therapy with an immunomodulator. The sample can be a biopsy sample such as a biopsy sample (e.g., a tumor biopsy sample) or a fecal sample. [00149] In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulator can include determining bacterial gene expression in the sample from the subject (e.g., a tumor biopsy sample). For example, the bacterial gene expression can be determined in the sample from the subject e.g., before administering to the subject an effective amount of a bacterial strain or a composition containing the bacterial strain and/or after administering to the subject an effective amount of a bacterial strain or a composition containing the bacterial strain. Determining the bacterial gene expression can include performing, for example, RNAseq and/or RT-qPCR. In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining bacterial composition in the sample from the subject (e.g., fecal sample or a biopsy sample such as tumor biopsy sample). For example, the bacterial composition can be determined in a sample from the subject, e.g., before administering to the subject an effective amount of a bacterial strain or a composition containing the bacterial strain and/or after administering to the subject an effective amount of a bacterial strain or a composition containing the bacterial strain. Determining the bacterial composition can include, for example, sequencing one or more nucleic acids from the bacteria. In some embodiments, bacteria can be identified by their 16S rRNA gene sequence.

[00150] In some embodiments, detecting the dysbiosis comprises determining that Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Melhanobrevibacler smithii TS96C, Oscillibacter sp. ER4, or a combination thereof, is decreased (e.g., reduced) in the sample from subject (e.g., decreased (e.g., reduced) in a fecal sample or a biopsy sample such as a tumor biopsy sample from the subject).

[00151] In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that Bacteroides sp. 14(A), Bacteroides stercoris A, Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, Bacteroides vulgatus 3975 RP4, Clostridium clostridioforme 90A7, Prevotella sp. 109, Ruminococcaceae bacterium GD6, Streptococcus parasanguinis R-4285, or a combination thereof, is increased (e.g., enriched) in the sample from subject. In some embodiments, detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that Bacteroides sp. 14(A), Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, Bacteroides vulgatus 3975 RP4, Clostridium clostridioforme 90 A7, Prevotella sp. 109, Ruminococcaceae bacterium GD6, Streptococcus parasanguinis R-4285, or a combination thereof, is increased (e.g., enriched) in the sample from subject.

[00152] In some embodiments, a method as provided herein can include decreasing a population of an increased (e.g., enriched) bacterial strain in a subject (e.g., a subject with cancer and/or undergoing therapy with an immunomodulator). In some embodiments, detecting the decrease in the population of an increased (e.g., enriched) bacterial strain comprises determining the bacterial composition in a sample from the subject (e.g., a tumor biopsy sample). For example, the bacterial composition can be determined in a sample from the subject before administering to the subject an effective amount of a bacterial strain or a composition containing the bacterial strain and after administering to the subject an effective amount of a bacterial strain or a composition containing the bacterial strain. For example, the population of an increased (e.g., enriched) bacterial strain can be decreased by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, or at least 50%, e.g., in a sample from the subject after administration of a bacterial strain or a composition containing the bacterial strain to the subject compared to before administration to the subject of an effective amount of a bacterial strain or a composition containing the bacterial strain. Determining the bacterial composition can include, for example, sequencing one or more nucleic acids from the bacteria. In some embodiments, bacteria can be identified by their 16S rRNA gene sequence.

[00153] In some embodiments, the enri increased (e.g., enriched) ched bacterial strain can be selected from the group consisting of Bacteroides sp. 14(A), Bacteroides stercoris A, Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, Bacteroides vulgatus 3975 RP4, Clostridium clostridioforme 90A7, Prevotella sp. 109, Ruminococcaceae bacterium GD6, Streptococcus parasanguinis R-4285, and a combination thereof. [00154] A complete genomic sequence for Bacteroides sp. 14(A) is available in the GenBank database as, e.g., Accession No. GCF 000526555. In some embodiments, the Bacteroides sp. 14(A) can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000526555. For example, Bacteroides sp. 14(A) can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000526555. In some embodiments, Bacteroides sp. 14(A) can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one, two, three, or all) of SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9 (e.g, at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more (e.g., one, two, three, or all) of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9).

[00155] A complete genomic sequence for Bacteroides stercoris A is available in the GenBank database as, e.g., Accession No. GCF 000154525. In some embodiments, the Bacteroides stercoris A strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000154525. For example, Bacteroides stercoris A can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000154525. In some embodiments, Bacteroides stercoris A has a 16S RNA gene that is at least 90% identical to one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, or all) of SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, and SEQ ID NO:20 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, or all) of SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, and SEQ ID NO:20).

[00156] A complete genomic sequence for Bacteroides thetaiotaomicron E50 is available in the GenBank database as, e.g., Accession No. GCF 000011065. In some embodiments, Bacteroides thetaiotaomicron E50 can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF OOOOl 1065. For example, Bacteroides thetaiotaomicron E50 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000011065. In some embodiments, Bacteroides thetaiotaomicron E50 can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, or all) of SEQ IDNO:21, SEQ IDNO:22, SEQ IDNO:23, SEQ IDNO:24, SEQ IDNO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, and SEQ ID NO:31 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, or all) of SEQ IDNO:21, SEQ IDNO:22, SEQ IDNO:23, SEQ IDNO:24, SEQ IDNO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, and SEQ ID NO:31).

[00157] A complete genomic sequence for Bacteroides thetaiotaomicron KLE1254 is available in the GenBank database as, e.g., Accession No. GCF 001578565. In some embodiments, Bacteroides thetaiotaomicron KLE1254 can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 001578565. For example, Bacteroides thetaiotaomicron KLE1254 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 001578565. In some embodiments, Bacteroides thetaiotaomicron KLE1254 can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:32 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:32).

[00158] A complete genomic sequence for Bacteroides vulgatus 3975 RP4 is available in the GenBank database as, e.g., Accession No. GCF 000699865. In some embodiments, the Bacteroides vulgatus 3975 RP4 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000699865. For example, Bacteroides vulgatus 3975 RP4 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000699865. In some embodiments, strain Bacteroides vulgatus 3975 RP4 can have a 16S RNA gene that is at least 90% identical to one or both of SEQ ID NO:33 and SEQ ID NO:34 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or both of SEQ ID NO:33 and SEQ ID NO:34).

[00159] A complete genomic sequence for Clostridium clostridioforme 90A7 is available in the GenBank database as, e.g., Accession No. GCF 000371525. In some embodiments, the Clostridium clostridioforme 90A7 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000371525. For example, Clostridium clostridioforme 90A7 RP4 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000371525. In some embodiments, strain Clostridium clostridioforme 90 A7 can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one, two, or all) of SEQ ID NO:35, SEQ ID NO:36, and SEQ ID NO:37 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more (e.g., one, two, or all) of SEQ ID NO:35, SEQ ID NO:36, and SEQ ID NO:37).

[00160] A complete genomic sequence for Prevotella sp. 109 is available in the GenBank database as, e.g., Accession No. GCF 001275135. In some embodiments, the Prevotella sp. 109 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 001275135. For example, Prevotella sp. 109 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 001275135. In some embodiments, strain Prevotella sp. 109 can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:38 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:38).

[00161] A complete genomic sequence for Ruminococcaceae bacterium GD6 is available in the GenBank database as, e.g., Accession No. GCF 001486165. In some embodiments, the Ruminococcaceae bacterium GD6 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 001486165. For example, Ruminococcaceae bacterium GD6 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 001486165. In some embodiments, strain Ruminococcaceae bacterium GD6 can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one, two, or all) of SEQ ID NO:39, SEQ ID NO:40, and SEQ ID NO:41 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more (e.g., one, two, or all) of SEQ ID NO:39, SEQ ID NO:40, and SEQ ID NO:41).

[00162] In some embodiments, strain Streptococcus parasanguinis R-4285 can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one, two, three, four, five, six, seven, or all) of SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, and SEQ ID NO:49 (e.g, at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more (e.g., one, two, three, four, five, six, seven, or all) of SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, and SEQ ID NO:49).

[00163] A complete genomic sequence for Ruminococcaceae bacterium AF10 16 is available in the GenBank database as, e.g., Accession No. GCF 003479765. In some embodiments, the Ruminococcaceae bacterium AFIO 16 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 003479765. For example, Ruminococcaceae bacterium AF 10 16 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 003479765. In some embodiments, strain Ruminococcaceae bacterium AFIO 16 can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:55 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:55).

[00164] A complete genomic sequence for Intestinimonas timonensis GD4 is available in the GenBank database as, e.g., Accession No. GCF 900626145. In some embodiments, the Intestinimonas timonensis GD4 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 900626145. For example, Intestinimonas timonensis GD4 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 900626145. In some embodiments, strain Intestinimonas timonensis GD4 an have a 16S RNA gene that is at least 90% identical to SEQ ID NO:56 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:56).

[00165] A complete genomic sequence for Faecalibacterium prausnitzii CNCM I 4546 is available in the GenBank database as, e.g., Accession No. GCF_002549935. In some embodiments, the Faecalibacterium prausnitzii CNCM I 4546 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 002549935. For example, Faecalibacterium prausnitzii CNCM I 4546 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 002549935. In some embodiments, strain Faecalibacterium prausnitzii CNCM I 4546 can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one, or two) of SEQ ID NO:57 and SEQ ID NO:58 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more of SEQ ID NO:57 and SEQ ID NO:58).

[00166] A complete genomic sequence for Bacteroides caccae AMI 649B is available in the GenBank database as, e.g., Accession No. GCF 003470705. In some embodiments, the Bacteroides caccae AM 1649B strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 003470705. For example, Bacteroides caccae AMI 6 49B can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 003470705. In some embodiments, strain Bacteroides caccae AMI 6 49B can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:60 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:60).

[00167] A complete genomic sequence for Barnesiella intestinihominis DSM 21032 is available in the GenBank database as, e.g., Accession No. GCF 000296465. In some embodiments, the Barnesiella intestinihominis DSM 21032 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000296465. For example, Barnesiella intestinihominis DSM 21032 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000296465. In some embodiments, strain Barnesiella intestinihominis DSM 21032 can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one, two, or all) of SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:63 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about

98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more (e.g., one, two, or all) of SEQ ID NO:61, SEQ ID NO:62 and SEQ ID NO:63).

[00168] A complete genomic sequence for Faecalibacterium prausnitzii AM33 14AC is available in the GenBank database as, e.g., Accession No. GCF 003434175. In some embodiments, the Faecalibacterium prausnitzii AM33 14 AC strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 003434175. For example, Faecalibacterium prausnitzii AM33 14AC can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF_003434175.

[00169] A complete genomic sequence for Clostridiaceae bacterium OM08 6BH is available in the GenBank database as, e.g., Accession No. GCF 003481535. In some embodiments, the Clostridiaceae bacterium OM08 6BH strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 003481535. For example, Clostridiaceae bacterium OM086BH can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 003481535. In some embodiments, strain Clostridiaceae bacterium OM08 6BH can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:65 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:65).

[00170] A complete genomic sequence for Ruminococcaceae bacterium TF06 43 is available in the GenBank database as, e.g., Accession No. GCF 003481145. In some embodiments, the Ruminococcaceae bacterium TF06 43 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 003481145. For example, Ruminococcaceae bacterium TF0643 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 003481145. In some embodiments, strain Ruminococcaceae bacterium TF06 43 can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:59 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:59).

[00171] A complete genomic sequence for Clostridium sp. AM33 3 is available in the GenBank database as, e.g., Accession No. GCF 003480315. In some embodiments, the Clostridium sp. AM33 3 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 003480315. For example, Clostridium sp. AM33 3 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 003480315. In some embodiments, strain Clostridium sp. AM33 3 can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:64 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:64). [00172] A complete genomic sequence for Bifidobacterium adolescentis 221 is available in the GenBank database as, e.g., Accession No. GCF 000737885 and GCF 002108045. In some embodiments, the Bifidobacterium adolescentis 221 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 000737885 or GCF 002108045. For example, Bifidobacterium adolescentis 221 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 000737885 or GCF 002108045. In some embodiments, strain Bifidobacterium adolescentis 221 can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one or two) of SEQ ID NO:50 and SEQ ID NO:51 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about

99.9% identical to one or more of SEQ ID NO:50 and SEQ ID NO:51).

[00173] A complete genomic sequence for Eisenbergiella massiliensis AT11 is available in the GenBank database as, e.g., Accession No. GCF 900243045. In some embodiments, the Eisenbergiella massiliensis AT 11 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 900243045. For example, Eisenbergiella massiliensis AT11 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 900243045. In some embodiments, strain Eisenbergiella massiliensis ATI 1 can have a 16S RNA gene that is at least 90% identical to one or more (e.g., one or two) of SEQ ID NO:52 and SEQ ID NO:53 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to one or more of SEQ ID NO:52 and SEQ ID NO:53).

[00174] A complete genomic sequence for Ruminococcus sp. OM05 7 is available in the GenBank database as, e.g., Accession No. GCF 003481625. In some embodiments, the Ruminococcus sp. OM05 7 strain can have a genomic sequence with at least about 95% sequence identity to the genomic sequence published as GCF 003481625. For example, Ruminococcus sp. OM05 7 can have a genomic sequence with at least about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the genomic sequence published as GCF 003481625. In some embodiments, strain Ruminococcus sp. OM05 7 can have a 16S RNA gene that is at least 90% identical to SEQ ID NO:54 (e.g., at least about 91%, about 91.5% about 92%, about 92.5%, about 93%, about 93.5%, about 94%, about 94.5%, about 95%, about 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% identical to SEQ ID NO:54).

[00175] In some embodiments, decreasing the population of an increased (e.g., enriched) bacterial strain can include administering a bacteriophage to the subject. See, for example, Sabino et al. Aliment Pharmacol Ther. 51(l):53-63, 2020. In some embodiments, decreasing the population of an increased (e.g., enriched) bacterial strain can include administering to the subject a composition comprising an effective amount of a bacterial strain (e.g., a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof.

[00176] In some embodiments, methods provided herein can include administering the composition that includes an effective amount of one or more bacterial strains to the subject at least once per day. For example, the composition can be administered two, three, four, or more times per day. In some embodiments, an effective amount of the bacterial strain is administered in one dose, e.g., once per day. In some embodiments, an effective amount of the bacterial strain is administered in more than one dose, e.g., more than once per day. In some embodiments, the method comprises administering the composition to the subject daily, every other day, every three days, or once a week.

[00177] In some embodiments, an effective amount of a bacterial strain (e.g., Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Melhanobrevibacler smithii TS96C, Oscillibacter sp. ER4, or a combination thereof) in a composition described herein can include at least about 1 xlO ³ CFU of the bacterial strain. For example, an effective amount of a bacterial strain can be at least about 1 xlO ³ , about 1 xlO ⁴ , about 1 xlO ⁵ , about 1 xlO ⁶ , about 1 xlO ⁷ , about 1 xlO ⁸ , about 1 xlO ⁹ , about 1 xlO ¹⁰ , about 1 xlO ¹¹ , about 1 xlO ¹² , about 1 xlO ¹³ , or about 1 xlO ¹⁴ CFU of the bacterial strain. In some embodiments, the effective amount of a bacterial strain in a composition described herein comprises about 1 xlO ³ to about 1 xlO ¹⁵ CFU of the bacterial strain (e.g., about 1 xlO ³ to about 1 xlO ⁶ , about 1 xlO ³ to about 1 xlO ⁸ , about 1 xlO ³ to about 1 xlO ¹⁰ , about 1 xlO ³ to about 1 xlO ¹² , about 1 xlO ³ to about 1 xlO ¹⁴ , about 1 xlO ⁷ to about 1 xlO ¹² , about 1 xlO ¹³ to about 1 xlO ¹⁵ , about 1 xlO ¹¹ to about 1 xlO ¹⁵ , about 1 xlO ⁹ to about 1 xlO ¹⁵ , about 1 xlO ⁷ to about 1 xlO ¹⁵ , or about 1 xlO ⁵ to about 1 xlO ¹⁵ CFU of the bacterial strain).

[00178] In some embodiments, methods provided herein can include administering a composition comprising a bacterial strain as described herein in combination with one or more other treatments of cancer and/or in combination with adjunct therapies such as a therapeutic agent. In some embodiments, the treatment of cancer can be one or more of surgery, ablation, radiation therapy, embolization, or a combination thereof. In some embodiments, the treatment of cancer and/or adjunct therapy can be a therapeutic agent such as a chemotherapeutic agent, a targeted therapy (e.g., a kinase inhibitor), an immunotherapy, or a combination thereof. The composition comprising a bacterial strain and any other treatments and/or adjunct therapies can be administered together (e.g., in the same formulation), or the composition comprising the bacterial strain can be administered concurrently with, prior to, or subsequent to, the one or more other treatments or adjunct therapies.

[00179] Non-limiting examples of chemotherapeutic agents include carboplatin, cisplatin, gemcitabine, methotrexate, paclitaxel, pemetrexed, lomustine, temozolomide, dacarbazine, and combinations thereof. Non-limiting examples of targeted therapies include afatinib dimaleate, bevacizumab, cetuximab, crizotinib, erlotinib, gefitinib, sorafenib, sunitinib, pazopanib, everolimus, dabrafenib, aldesleukin, interferon alfa-2b, peginterferon alfa-2b, trametinib, vemurafenib, and combinations thereof. Non-limiting examples of an immunotherapy include an immune checkpoint inhibitor (e.g,. ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, and combinations thereof); co-stimulatory immune checkpoint agent (e.g., IBIIOI, utomilumab, MEDI1873, and combinations thereof); and a cell therapy (e.g., a CAR T-cell therapy).

[00180] In some embodiments, a prebiotic and/or probiotic can be administered in combination with a composition comprising a bacterial strain as described herein. Non limiting examples of a probiotic include one of more of Bifidobacteria (e.g., B. animalis , B. breve , B. lactis , B. longum , or . infantis ), Lactobacillus (e.g., L. acidophilus , L. reuteri , L. bulgaricus , L. lactis , L. casei, L. rhamnosus , L. plantar um, L. paracasei, or L. delbreuckii/bulgaricus ), Saccharomyces boulardii , E.coli Nissle 1917, and Streptococcus thermophiles. Non-limiting examples of a prebiotic include a fructooligosaccharide (e.g., oligofructose, inulin, or an inulin-type fructan), a galactooligosaccharide, an amino acid, or an alcohol. See, for example, Ramirez-Farias et al. (2008. Br. JNutr. 4:1-10) and Pool- Zobel and Sauer (2007. JNutr. 137:2580-2584).

[00181] In some embodiments, methods provided herein can include monitoring the subject after treatment with a composition described herein to determine if one or more symptoms have been alleviated, if the severity of one or more symptoms has been decreased (e.g., reduced), or if progression of the disease has been delayed or inhibited in the subject. There are numerous scores and clinical markers that can be utilized to assess the efficacy of administering a composition that includes bacterial strain as described herein in treating colorectal cancer.

[00182] In some embodiments, an effective amount of the therapeutic agent is administered in combination with a composition comprising a bacterial strain as described herein.

[00183] As an example, tumor or lesion size can be monitored. Any procedure that allows an assessment of the tumor or lesion size can be used. Non-limiting examples include digital rectal exam, an endoscopy (e.g., a colonoscopy), and imaging (e.g., PET, MRI, ERUS, DRE, CT). See, for example, McKeown et al. J Cancer. 2014\ 5(1): 31-43. In some embodiments, tumor burden can be assessed using RECIST (e.g., RECIST version 1 or version 1.1). See, for example, Eisenhauer et al., Eur J. Cancer. 45(2):228-47 (2009). Criteria for evaluating immunotherapy have also been developed. Non-limiting examples include the immune-related response criteria (irRC) (see Wolchok et al. Clin Cancer Res. 2009 Dec l;15(23):7412-20) and immune response criteria in solid tumors (iRECIST) criteria (see Seymour et al. Lancet Oncol. 2017 Mar; 18(3): el43-el52). See also, Thallinger et al. Wien Klin Wochenschr. 2018; 130(3): 85-91. In some embodiments, an increase in the response to an immunomodulator (e.g., an immune checkpoint inhibitor therapy and/or a co-stimulatory immune checkpoint therapy described herein) in a subject in need thereof is determined using, for example, any of the methods known to one of skill in the art for evaluating an immunotherapy such as those described herein. For example, a tumor in a subject receiving immunotherapy may decrease in size after administration of a composition comprising a bacterial strain as described herein relative to the size of the tumor prior to administration of a composition comprising a bacterial strain. In some embodiments, growth of a tumor in a subject receiving immunotherapy may decrease in size after administration of a composition comprising a bacterial strain as described herein relative to the size of the tumor prior to administration of a composition comprising a bacterial strain.

[00184] In some embodiments, compositions provided herein can include one or more excipients and can be formulated for any of a number of delivery systems suitable for administration to a subject (e.g., probiotic or LBP delivery systems). Non-limiting examples of an excipient include a buffering agent, a diluent, a preservative, a stabilizer, a binding agent, a filler, a lubricant, a dispersion enhancer, a disintegrant, a lubricant, a disintegrant, a wetting agent, a glidant, a flavoring agent, a sweetener, and a coloring agent. For example, in some embodiments, tablets or capsules can be prepared by conventional means with excipients such as binding agents, fillers, lubricants, disintegrants, or wetting agents. Any of the compositions described herein can be administered to a subject to treat cancer as described herein. [00185] In some embodiments, a composition as described herein can be formulated for oral delivery. In some embodiments, the composition can be formulated as a tablet, a chewable tablet, a capsule, a stick pack, a powder, effervescent powder, or a liquid. In some embodiments, a composition can include coated beads that contain the bacterial strain. In some embodiments, a powder comprising the bacterial strain can be suspended or dissolved in a drinkable liquid such as water for administration. In some embodiments, the composition is a solid composition.

[00186] In some embodiments, a composition described herein can be formulated for various immediate and controlled release profiles of the bacterial strain. For example, a controlled release formulation can include a controlled release coating disposed over the bacterial strain. In some embodiments, the controlled release coating is an enteric coating, a semi-enteric coating, a delayed release coating, or a pulsed release coating. In some embodiments, a coating can be suitable if it provides an appropriate lag in active release (i.e., release of the bacterial strain). For example, in some embodiments, the composition can be formulated as a tablet that includes a coating (e.g., an enteric coating).

[00187] In some embodiments, the composition can be formulated for topical delivery. In some embodiments, the composition can be in the form of a paste, gel, cream, spray, suppository, mousse, emollient, ointment, foam, or suspension.

[00188] In some embodiments, the compositions can be formulated for intravenous or intratumoral delivery.

[00189] In some embodiments, the bacterial strain in the composition is a culture of a single strain of organism. In some embodiments, the composition comprises a bacterial strain that is isolated. In some embodiments, the bacterial strain is isolated and cultured in vitro to increase the number or concentration of the bacterial strain. Increasing the number or concentration of the bacterial strain can be useful, for example, to enhance the therapeutic efficacy of a composition comprising the bacterial strain.

[00190] In some embodiments, an effective amount of the bacterial strain in a composition described herein comprises at least about 1 xlO ³ CFU of the bacterial strain. For example, at least about 1 xlO ³ , about 1 xlO ⁴ , about 1 xlO ⁵ , about 1 xlO ⁶ , about 1 xlO ⁷ , about 1 xlO ⁸ , about 1 xlO ⁹ , about 1 xlO ¹⁰ , about 1 xlO ¹¹ , about 1 xlO ¹² , about 1 xlO ¹³ , or about 1 xlO ¹⁴ CFU of the bacterial strain. In some embodiments, the effective amount of a bacterial strain in a composition described herein comprises about 1 xlO ³ to about 1 xlO ¹⁵ CFU of the bacterial strain. For example, about 1 xlO ³ to about 1 xlO ⁶ , about 1 xlO ³ to about 1 xlO ⁸ , about 1 xlO ³ to about 1 xlO ¹⁰ , about 1 xlO ³ to about 1 xlO ¹² , about 1 xlO ³ to about 1 xlO ¹⁴ , about 1 xlO ⁷ to about 1 xlO ¹² , about 1 xlO ¹³ to about 1 xlO ¹⁵ , about 1 xlO ¹¹ to about 1 xlO ¹⁵ , about 1 xlO ⁹ to about 1 xlO ¹⁵ , about 1 xlO ⁷ to about 1 xlO ¹⁵ , or about 1 xlO ⁵ to about 1 xlO ¹⁵ CFUs of the bacterial strain.

[00191] In some embodiments, the composition can include one or more biologically pure strains (e.g., two or more, three or more, or four or more bacterial strains). For example, the composition can include biologically pur Q Bifidobacterium sp. 12 1 47BFAA, biologically pure Collinsella sp. 4847FAA, biologically pure Methanobrevibacter smithii TS96C, biologically pure Oscillibacter sp. ER4, or any combination thereof.

[00192] In some embodiments, the composition is a solid composition that includes at least 1 xlO ³ CFU of a bacterial strain (e.g., a biologically pure strain) and one or more excipients. Identifying characteristics of suitable strains, including homology to 16S rRNA sequences are described above.

[00193] In some embodiments, each member of the same bacterial strain has a 16S rRNA gene sequence with at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or about 99.9% sequence identity to the 16S rRNA gene sequence of each other member of the same bacterial strain.

[00194] In some embodiments, a bacterial strain in a composition described herein is preserved. Methods for preserving bacterial strains can include lyophilization and cryopreservation, optionally in the presence of a protectant. Non-limiting examples of protectants include sucrose, inulin, and glycerol. In some embodiments, a composition can include a lyophilized or cryopreserved bacterial strain such as Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, or a combination thereof, and an optional protectant.

[00195] In some embodiments, wherein the bacterial strain is a combination of two or more of: Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4, one or more of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4 are lyophilized or cryopreserved.

[00196] In some embodiments, the composition is a live bacterial product (LBP). In some embodiments, the bacterial strain in the composition is viable. The viable bacterial strain may be, for example, cryopreserved and/or lyophilized. In some embodiments, a composition for delivery of live bacterial strains (e.g., Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, or a combination thereof), can be formulated to maintain viability of the bacterial strain. In some embodiments, the composition comprises elements that protect the bacterial strain from the acidic environment of the stomach (e.g., an enteric coating).

[00197] In some embodiments, wherein the bacterial strain is a combination of two or more of: Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA,

Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4, one or more of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4 are viable.

[00198] In some embodiments, the bacterial strain in the composition can be non- viable. In some embodiments, the non-viable bacterial strain is heat-killed, irradiated, or lysed. [00199] In some embodiments, wherein the bacterial strain is a combination of two or more of: Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA,

Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4, one or more of

Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, and Oscillibacter sp. ER4 are non-viable (e.g., heat-killed, irradiated, or lysed). [00200] In some embodiments, the bacterial strain as described herein may be used in prophylactic applications. For example, in a prophylactic application, a bacterial strain or a composition described herein can be administered to a subject susceptible to, or otherwise at risk of, a particular disease in an amount that is sufficient to at least partially reduce the risk of developing a disease. One of ordinary skill in the art will appreciate that the precise amounts of the bacterial strain administered may depend on a number of subject specific factors such as the subject's state of health and/or weight.

[00201] Also provided herein are methods of treating cancer in a subject that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve orjbacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and (b) administering a cancer treatment that excludes an immunomodulator as a monotherapy to the identified subject.

[00202] Also provided herein are methods of treating cancer in a subj ect that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and (b) administering a therapeutically effective amount of a bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihommis, Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Ruminococcaceae bacterium , Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., Bifidobacterium adolescentis , and a combination thereof, and an immunomodulator as a monotherapy or in conjunction with another anticancer agent to the identified subject. [00203] Also provided herein are methods of treating cancer in a subject that include administering to a subject identified as having (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihommis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis , a therapeutically effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihommis , Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., Bifidobacterium adolescentis 221, and a combination thereof, and an immunomodulatory as a monotherapy or in conjunction with another anticancer agent. [00204] Also provided herein are methods of treating cancer in a subject that include administering to a subject identified as having (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis a cancer treatment that excludes an immunomodulatory as a monotherapy.

[00205] Also provided herein are methods of treating a cancer in a subject that has previously received one or more doses of an immunomodulator, wherein the method comprises administering to a subject identified as having: (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis; a cancer treatment that excludes an immunomodulator as a monotherapy.

[00206] Also provided herein are methods of treating a cancer in a subject that has previously received one or more doses of an immunomodulator, wherein the method comprises administering to a subject identified as having: (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis; a therapeutically effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihominis , Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., Bifidobacterium adolescentis 221, and a combination thereof, and an immunomodulator as a monotherapy or in conjunction with another anticancer agent.

[00207] Also provided herein are methods of treating cancer in a subj ect, the method comprising: (a) administering one or more doses of an immunomodulator for a period of time; (b) after (a), determining whether a sample obtained from a subject having cancer has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and (c) administering a therapeutically effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihominis , Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae , Clostridiaceae bacterium , Clostridium sp., Bifidobacterium adolescentis 221, and a combination thereof, and an immunomodulator as a monotherapy or in conjunction with another anticancer agent. [00208] Also provided herein are methods for identifying a subject as having an decreased likelihood of having a positive response to treatment with an immunomodulator, the method comprising: a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis , as having an decreased likelihood of having a positive response to treatment with an immunomodulator.

[00209] In some embodiments, the level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis are increased in comparison to the same bacterial species in a reference sample.

[00210] In some embodiments, the level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis are decreased in comparison to the same bacterial species in a reference sample. [00211] In some embodiments, the level of one or more (e.g., two or more, or three) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., and Streptococcus parasanguinis are increased in comparison to the same bacterial species in a reference sample. [00212] In some embodiments, the level of one or more (e.g., two or more, three or more, or four) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , and Oscillibacter sp. are decreased in comparison to the same bacterial species in a reference sample.

[00213] In some embodiments, the level of one or more bacterial species selected from the group consisting of: Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis are increased in comparison to the same bacterial species in a reference sample.

[00214] In some embodiments, the level of the bacterial species selected from the group consisting of: Barnesiella intestinihominis, Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae, Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis is decreased in comparison to the same bacterial species in a reference sample. [00215] Also provided herein are methods of treating cancer in a subject that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp. , Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and (b) administering an immunomodulator as a monotherapy or in conjunction with another anticancer agent to the subject.

[00216] Also provided herein are methods of treating cancer in a subject that include administering to a subject identified as having (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp. , Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis , a therapeutically effective amount of an immunomodulatory as a monotherapy or in conjunction with another anticancer agent. [00217] Also provided herein are methods for identifying a subject as having an increased likelihood of having a positive response to treatment with an immunomodulator that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis, as having an increased likelihood of having a positive response to treatment with an immunomodulator. [00218] Also provided herein are methods for selecting an immunomodulator for a subj ect that include (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and selecting an immunomodulator for the identified subject. [00219] Also provided herein are methods for selecting a subject for treatment with an immunomodulator comprising (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and selecting the identified subject for treatment with an immunomodulator.

[00220] Also provided herein are methods for selecting a subject for participation in a clinical study comprising administration of an immunomodulator, (a) identifying a subject having a sample that has (i) an increased level of one or more (e.g. two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Barnesiella intestinihominis , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis ; and/or (ii) a decreased level of one or more (e.g. two or more, three or more, four or more, five or more, or six) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis ; and selecting the identified subject for participation in a clinical study comprising administration of an immunomodulator.

[00221] In some embodiments, the level of the bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , Oscillibacter sp., Barnesiella intestinihominis, Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Bacteroides caccae, Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis are increased in comparison to the same bacterial species in a reference sample.

[00222] In some embodiments, the level of one or more bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., Streptococcus parasanguinis, Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis are decreased in comparison to the same bacterial species in a reference sample.

[00223] In some embodiments, the level of one or more (e.g. two or more, or three) bacterial species selected from the group consisting of: Clostridium clostridioforme , Prevotella sp., and Streptococcus parasanguinis are decreased in comparison to the same bacterial species in a reference sample.

[00224] In some embodiments, the level of one or more (e.g. two or more, three or more, or four) bacterial species selected from the group consisting of: Bifidobacterium sp., Collinsella sp., Methanobrevibacter smithii , and Oscillibacter sp. are increased in comparison to the same bacterial species in a reference sample.

[00225] In some embodiments, the level of one or more bacterial species selected from the group consisting of: Anaerostipes hadrus, Parasutterella excrementihominis, and Eisenbergiella massiliensis are decreased in comparison to the same bacterial species in a reference sample.

[00226] In some embodiments, the level one or more bacterial species selected from the group consisting of: Barnesiella intestinihominis, Faecalibacterium prausnitzii C, Faecalibacterium prausnitzii I, Intestinimonas timonensis , Faecalibacterium prausnitzii , Clostridiaceae bacterium , Clostridium sp., and Bifidobacterium adolescentis is increased in comparison to the same bacterial species in a reference sample.

[00227] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. EXAMPLES

[00228] Example 1. Identification of bacterial species and strains associated with checkpoint inhibitor therapy

[00229] A multiple-technology meta-analysis (MTMA) approach was applied to datasets, which led to the identification of strains unique to responders and non-responders to checkpoint inhibitor therapy. To overcome challenges of comparing clinical variables across datasets from multiple institutes, a controlled vocabulary of hierarchically organized terms and manually re-annotated metadata from public datasets using this vocabulary was created. FIG. 7 provides the details regarding the cohorts, datasets, and contrasts analyzed to identify differentially abundant (DA) taxa correlating with disease progression. Statistical analysis of each dataset was performed using the workflow described in FIG. 1. Strain-level annotation was achieved using StrainSelect, a database containing sequence information of bacterial and archaeal strains connected to genome identifiers, which facilitated comparative analysis of taxa abundances at a strain-level across datasets [00230] Methods

[00231] Procurement of raw data and metadata curation

[00232] Fastq/Fasta files and metadata were procured from public repositories. Metadata stored with raw data, such as NCBf s Runlnfo table associated with the SRA Run Selector, and/or metadata published in tables in the primary text or supplementary files of the publication, were retrieved and manually re-annotated using a controlled vocabulary of hierarchically organized terms. An in-house database was created to store all study-related data and facilitate appropriate metadata annotation of all datasets via manual curation. Clinical metadata was stored in this database as a series of labehvalue pairs attached to the biospecimen from which the data files were generated.

[00233] Processing strain annotation and statistical analyses of raw data [00234] 16S rRNA sequencing datasets ( 16S-NGS and 16S-Sanser)

[00235] Raw sequence reads were processed via DADA2 applying default settings for filtering, learning errors, dereplication, amplicon sequence variant (ASV) inference, and chimera removal (Callahan et al. Nat. Methods 13, 581-583 (2016)). Truncation quality (truncQ) was set to two, and ten nucleotides were trimmed from the termini of each forward and reverse read. ASVs where mapped to an in-house strain database (StrainSelect, strainselect.secondgenome.com, version 2016 (SS16)) using USEARCH (usearch global) (Edgar. Bioinformatics 26, 2460-2461 (2010)). All sequences matching a unique strain at an identity > 99% was assigned a strain-level annotation. To ensure specificity of these strain matches, a difference of > 0.25% between the identity of the best match and the second best match was required e.g., 99.75 vs. 99.5). StrainSelect is a repository of strain identifiers obtained from gene sequencing, genome sequencing, draft genomes, and metagenomic assemblies of known prokaryotic strains. [00236] Downstream of a 5% prevalence filter, DESeq2 (Wood and Salzberg.

Genome Biol. 15, R46 (2014)) was used to calculate significant differences in isolated analysis across all bins (OTUs, ASVs and strains) and adjusted p-values were determined with the Benjamini-Hochberg correction. Significant results were determined as adjusted p-values < 0.05. Log 2 fold change and standard error were calculated via DESeq2 and applied to subsequent analyses. [00237] Metagenomic datasets (WGS-NGS)

[00238] Reads were processed with Trimmomatic (Bolger et al. Bioinformatics 30, 2114-2120 (2014)) to remove adapter sequences and low-quality ends (< Q20). Reads shorter than 35-bp following trimming were discarded. Contaminant sequences ( e.g sequencing primers) were removed using Bowtie (Langmead et al. Nat. Methods 9, 357- 359 (2012)). Host sequences were removed via Kraken (Wood et al. Genome Biol. 15, R46 (2014)), which used exact alignments of raw shotgun sequences to k-mers derived from the human reference genome. Ribosomal RNA sequences from all three domains of life were identified and removed with SortMeRNA 2.0 (Kopylova et al. Bioinformatics 28, 3211-3217 (2012)). Raw, non-host reads were considered, while low quality reads and ribosomal RNA reads were ignored. Sourmash was used to taxonomically annotate the datasets subjected to metagenomic analysis (see, Titus Brown et al. Open Source Softw. 1, 27 (2016)). StrainSelect database version 2016 (SSI 6) was used to map genome assembly identifiers to strain-level annotations. [00239] A 5% prevalence filter was applied to all bin (Sourmash generated taxon)- count tabulations. If a bin passed prevalence filtration yet went undetected in any of the samples within a particular contrast group, a pseudocount (the minimum relative abundance value observed in the dataset divided by 1000) was added to one random sample in that group. Wilcoxon-rank sum tests were applied to identify statistically significant differences in each bin, and p-values were Benjamini-Hochberg-corrected to adjust for false discovery. Significant results for isolated analysis were determined as adjusted p- values < 0.05. Fold change, variance and standard error were calculated as described above. [00240] Multi-technology meta-analysis

[00241] Log 2 fold change and standard errors pertaining to per-dataset statistical results in each disease area were integrated in MTMA using a Random effects model (REM), generated using the metafor R package. Only bins with strain-level annotations in each dataset, and only those strains observed in at least two datasets, post prevalence filtering, were retained for REM analysis. False discovery correction for REM generated p-values was achieved using the Benjamini-Hochberg method. Differences are deemed to be statistically significant at adjusted (Benjamini-Hochberg corrected) p-values < 0.05 in both isolated dataset analysis and MTMA.

[00242] Results [00243] Identification of differentially abundant strains across cohorts from a simple comparison of isolated datasets was limited as less than 5% of the strains were detected across all datasets (FIG. 2, top panel). Further, isolated analysis identified only 1 strain as significantly differentially abundant and this association was cohort-specific (FIG. 2, middle panel). Variation was also observed in the magnitude of differential abundance derived from the cohorts and especially the profiling technologies (log 2 fold change; FIG.

3)·

[00244] Strain-level results were integrated from isolated analyses in each disease via MTMA as described in FIG. 1. Significant associations were identified only when the direction of differential abundance of the strain was supported by multiple datasets (FIG. 4; blue strains connected to MTMA nodes via thick-solid lines). The associations in isolated analyses that were not supported in trend by other datasets were not significant by MTMA (FIG. 4; dark-green circles). Several strain-disease associations identified in MTMA were not identified in isolated analyses of the datasets (FIG. 4; purple dots). Thus, MTMA corroborates findings from isolated analysis if supported across datasets but eliminates if discordant, and MTMA identifies novel disease-strain associations that isolated analyses failed to detect.

[00245] Several strains were identified as significantly associated with response to therapy with an immunomodulator. In contrast, only one strain ( Bacteroides stercoris A) was identified in the isolated analysis indicating these studies individually were underpowered to detect significant differences at the strain-level. While limited overlap has been observed across bacterial taxa reported as being associated with response to immune checkpoint inhibitors in published studies (Gopalakrishnan et al. Cancer Cell 33, 570-580 (2018)), the response-associated strains identified herein, such as Oscillibacter sp. ER4 that were consistently associated with treatment response across all datasets, are candidate biomarkers for subj ect stratification for therapy with an immunomodulator (FIG. 5). MTMA identified a greater number of increased (e.g., enriched) bacterial strains compared to decreased (e.g., reduced) bacterial strains in dysbiotic conditions associated with response to therapy with an immunomodulator in melanoma (FIG. 6).

[00246] MTMA can enable synthesis of existing knowledge of the microbiome, and the approach as shown in FIG. 1 can facilitate comparative analysis of taxa abundances at a strain-level across datasets generated with different DNA-profiling technologies. Harnessing the MTMA framework, with its ability to integrate datasets across DNA- profiling technologies and pinpoint specific strains, can allow for identification of robust microbiome modulators of disease by integrating the growing body of evidence on the role played by microbiome in disease.

[00247] Example 2. Identification of bacterial species and strains associated with checkpoint inhibitor therapy

[00248] A geographically dispersed meta-cohort of melanoma patients made up of both previously published and original cohorts (N=188) was assembled. Using stool samples collected pre-treatment, a systematic search for the best machine learning models over different patient subsets annotated with taxonomic and functional microbial features was performed. The lead model is able to classify patients with high accuracy (AUC=0.87), independently of clinical data and outperforming established biomarkers. The resulting microbial signature highlights novel markers of response, generalizing well across cohorts. This composite biomarker provides a robust non-invasive method for patient response prediction in melanoma.

[00249] In order to profile the microbiomes of the meta-cohort, taxonomic and functional features from metagenomic sequencing data derived from baseline stool samples were extracted. A large-scale curation effort integrated the microbiome and clinical data from each patient and standardized the endpoint definition of every study in the meta cohort. Several patient subsets within the meta-cohort based on ICI target type, disease stage, and exclusion of partial responders from the responder group were defined. FIG. 9 shows a schematic of the study design. [00250] Methods

[00251] Meta-cohort assembly

[00252] The meta-cohort was assembled from four previously published studies and two prospective studies. Gopalakrishnan et al. Science. 2018; 359(6371):97-103; Matson et al. Science. 2018; 359(6371): 104-108; Frankel et al. Neoplasia. 2017; 19(10):848-855; and Peters et al. studies were selected on the basis of availability of gut microbiome metagenomics (MTG) data from melanoma patients undergoing immune checkpoint inhibitor therapy. MTG data from each of these studies were obtained from NCBI under the Sequence Read Archive accession numbers. Two additional prospective cohorts were recruited at the University of Zurich and Stanford University. All baseline fecal MTG samples from each study were retained. Patients having undergone surgical resection of the tumor and receiving ICI treatment as an adjuvant were excluded from the meta-cohort. [00253] Patient subsets

[00254] A number of patient subsets were defined within the meta-cohort, based on clinical characteristics that may influence microbiome composition. These characteristics were metastasis status, immune checkpoint inhibitor therapy group, and the inclusion of partial responders in the responder group. Metastasis status was inferred from the publication (Frankel et al. & Peters et al. cohorts) or AJCC staging system (Matson et al., Gopalakrishnan et al., Stanford & UZH cohorts). Immune checkpoint inhibitor treatment strategies were categorized as anti -PD- 1 (patients receiving Pembrolizumab, Nivolumab, Avelumab, Cemiplimab, or Infliximab), anti -PD- 1 combination therapy (patients receiving Ipilimumab & Nivolumab or Dabrafenib & Trametinib) or anti-CTLA-4 (patients receiving Ipilimumab).

[00255] Assessment of response to immune checkpoint inhibitor treatment is based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1), administered at 6 months after the start of ICI therapy. Patients exhibiting complete response or progressive disease were categorized as Responders (R) and Non-Responders (NR) respectively. Patients with stable disease or mixed response were categorized as Partial Responders (PR). Peters et al. provided progression-free survival (PFS) data, from which Responders and Non- responders were categorized based on PFS greater or less than 6 months, respectively. [00256] Microbiome profiling

[00257] Raw FASTQ reads from all cohorts were systematically re-processed using Second Genome’s metagenomics pipeline.

[00258] Data pre-processing [00259] Missing clinical information was imputed using the meta-cohort’ s mean value in the case of continuous values (age) or most frequent value in the case of categorical features (sex and metastatic status).

[00260] Microbial taxonomic or functional features with low prevalence (defined as occurrence in 20% or fewer of patients) were discarded. The remaining features were normalized using total sum scaling (TSS) normalization. Finally, for each of the patient subsets identified above, we performed feature selection using a combination of student’s t-test and block HSIC Lasso et al.

[00261] Machine Learning

[00262] A cloud-based machine-learning platform was developed to interrogate the various patient cross sections in the meta-cohort. Each patient subset was annotated with every possible combination of the available clinical, taxonomic, and functional features. The resulting training sets were then used to train two algorithm types: a support vector machine (SVM) and a LightGBM gradient-boosted tree. For SVM models, training set data was scaled using sci-kit learn’ s StandardScaler prior to training. Models were trained using a five-fold cross-validation grid search with hyper-parameter tuning. The average metrics over each of the five folds for the best model out of the hyperparameter grid search are reported.

[00263] A second round of feature reduction was applied to trained models of interest. One to twenty features were retained from the classifier ranked information gain features, and the model was re-trained using five-fold cross-validation as described above.

[00264] Model Validation

[00265] Leave-one-out cohort analysis was performed where each of the cohorts were left out of the training set and the model re-trained on the chosen set of features. [00266] Results [00267] Taxonomic and functional annotations were consistently re-processed + re analyzed using the bioinformatics pipeline. The dataset shows clustering by cohort is stronger than clustering by response label. A number of subsets in the meta-cohort were identified that may drive observed differences in the microbiome: metastatic, treatment type and partial responders.

[00268] Machine learning-based exploration of meta-cohort feature space enables the identification of the most pertinent features for ICI response prediction, beyond cohort biases. Stool metagenomic (MTG) data was systematically re-processed to generate taxonomic and functional profiles of the gut microbiome of 6 geographically-dispersed cohorts (N = 166). Uniform Manifold Approximation and Projection (UMAP) projection of the functional and taxonomic profiles of the meta-cohort microbiomes show little responder class segregation and evidence of cohort biases (FIG. 10). Multiple cross- sections of the meta-cohort were analyzed with different combinations of features by training supervised learning algorithms. [00269] The results indicate that microbial features are sufficient to achieve a high classification accuracy independently of clinical information, such as age and sex. Microbial features alone yield strong patient classification performance, independently of clinical information. Additionally, the exclusion of partial responders from the responder group yielded better classification performance. This indicates that signal of response is more clearly defined in the microbiome of complete responders than of partial responders. Partial responders are more difficult to classify (FIG. 11).

[00270] Striking differences between classifiers for different treatment groups (aPDl only, aPDl & cocktails, or aPDl together with aCTLA-4) were not observed. Also, no significant differences in metastatic or not subsets were observed. These are also explained by the limited size of these subsets: only 13 non-metastatic patients and a handful of aCTLA4 samples.

[00271] The highest classification performance was observed in late stage, metastatic disease (area under the curve, AUC > 0.8). Importantly, the identified microbial signature in several patient subsets largely overlapped, indicating that microbiome markers of response are not dependent on age, sex, ICI treatment type or partial responder status. Furthermore, the models distinguish non-responders from both complete and partial responders.

[00272] Model classification metrics showed a high predictive power from microbial features alone. Microbial features alone yield strong patient classification performance, independently of clinical features (FIG. 11). The exclusion of partial responders from the training set further improved results. (FIG. 12)

[00273] A second round of feature selection was applied. Models were iteratively re trained using five-fold cross-validation with diminishing number of features (from 20 to three). The performance of the model with each N features was recorded. Following this second round, models with an AUC > 0.8 were retained. One model had AUC = 0.828 and relies on only 5 markers of functional features.

[00274] Refinement of the lead model yielded a high-performing composite biomarker of 5 microbial functional units. Each cohort was left out of the final model to assess performance across cohorts (FIG. 13). UMAP projection of the composite biomarker features for the meta-cohort shows separation of responder class labels and little cohort clustering (FIG. 14). ROC curve on validation set shows an AUC of 0.69 (FIG. 15).

[00275] The biomarker features are shown in Table X. Expression heatmap of the 20 features, clinical data, and responder status (FIG. 16). FIG. 17 shows feature effect size. [00276] Table X

R=Responder; NR=N on-Responder

OTHER EMBODIMENTS

1. A method for treating a subject in need thereof, the method comprising administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof. 2. A method for increasing the response to an immunomodulator in a subject in need thereof that includes administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof.

3. The method of embodiment 1 or 2, wherein the subject has cancer.

4. A method for treating cancer in a subject, the method comprising administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof.

5. A method for treating cancer in a subject, the method comprising: (a) detecting a dysbiosis associated with response to therapy with an immunomodulator in a sample from the subject; and

(b) administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof.

6. The method of embodiment 5, wherein the sample is a fecal sample. 7. The method of embodiment 5, wherein the sample is a tumor biopsy sample.

8. The method of any one of embodiments 5-7, wherein detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining bacterial gene expression in the sample from the subject.

9. The method of any one of embodiments 5-8, wherein detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining bacterial composition in the sample from the subject. 10. The method of embodiment any one of embodiments 5-9, wherein detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that Bacteroides sp. 14(A), Bacteroides stercoris A, Bacteroides thetaiotaomicron E50, Bacteroides thetaiotaomicron KLE1254, Bacteroides vulgatus 3975 RP4, Clostridium clostridioforme 90 A7, Prevotella sp. 109, Ruminococcaceae bacterium GD6, Streptococcus parasanguinis R-4285, or a combination thereof, is increased in the sample from subject.

11. The method of embodiment any one of embodiments 5-10, wherein detecting the dysbiosis associated with response to therapy with an immunomodulator comprises determining that Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, or a combination thereof, are depleted in the sample from subject.

12. The method of embodiment 11, wherein Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, or a combination thereof, are depleted in the gastrointestinal tract of the subject.

13. A method for treating a subject in need thereof, the method comprising decreasing a population of an increased bacterial strain in the subject, wherein the increased bacterial strain is selected from the group consisting of: Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 847FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof.

14. The method of embodiment 13, wherein the subject has cancer.

15. The method of any one of embodiments 13-14, wherein decreasing the population of an increased bacterial strain comprises administering to the subject a bacteriophage.

16. The method of any one of embodiments 13-15, wherein decreasing the population of an increased bacterial strain comprises administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4847FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof.

17. The method of any one of embodiments 1-16, wherein the subject is undergoing therapy with an immunomodulator.

18. A method for treating cancer in a subject, the method comprising administering to the subject a composition comprising an effective amount of a bacterial strain selected from the group consisting of: Bifidobacterium sp. 12 1 47BFAA, Collinsella sp. 4 8 47FAA, Methanobrevibacter smithii TS96C, Oscillibacter sp. ER4, and a combination thereof, wherein the subject is undergoing therapy with an immunomodulator.

19. The method of embodiment 17 or 18, wherein the immunomodulator targets one or more of: CTLA-4, PD-1, PD-L1, BTLA, LAG-3, A2AR, TIM-3, B7-H3, VISTA, IDO,

0X40, 4- IBB, and GITR.

20. The method of any one of embodiments 2-12 and 14-19, wherein the subject has a solid tumor.

21. The method of embodiment 20, wherein the subj ect has a solid tumor selected from the group consisting of: melanoma, lung cancer, kidney cancer, bladder cancer, a head and neck cancer, Merkel cell carcinoma, urothelial cancer, breast cancer, glioblastoma, gastric cancer, a nasopharyngeal neoplasm, colorectal cancer, hepatocellular carcinoma, ovarian cancer, and pancreatic cancer.

22. The method of any one of embodiments 2-12 and 14-19, wherein the subject has a hematological malignancy. 23. The method of embodiment 22, wherein the subject has a hematological malignancy selected from the group consisting of: multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). 24. The method of any one of embodiments 2-12 and 14-23, wherein the subject has a cancer selected from one or more of: melanoma, non-small cell lung cancer (NSCLC), small cell lung cancer, squamous cell lung carcinoma, kidney cancer, bladder cancer, a head and neck cancer, Hodgkin lymphoma, Merkel cell carcinoma, urothelial cancer, breast cancer, glioblastoma, gastric adenocarcinoma, transitional cell carcinoma, a biliary tract neoplasm, a nasopharyngeal neoplasm, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and pancreatic cancer.

25. The method of embodiment 21 or 24, wherein the melanoma is unresectable or metastatic melanoma.

26. The method of any one of embodiments 1-12 and 16-25, wherein the bacterial strain comprises Bifidobacterium sp. 12 1 47BFAA. 27. The method of any one of embodiments 1-12 and 16-26, wherein the bacterial strain comprises Collinsella sp. 4 8 47FAA.

28. The method of any one of embodiments 1-12 and 16-27, wherein the bacterial strain comprises Methanobrevibacter smithii TS96C.

29. The method of any one of embodiments 1-12 and 16-28, wherein the bacterial strain comprises Oscillibacter sp. ER4.

30. The method of any one of embodiments 1-12 and 16-29, wherein the bacterial strain improves intestinal barrier function of the subject.

31. The method of any one of embodiments 1-12 and 16-30, wherein the bacterial strain modulates immune cell function in the subject. 32. The method of any one of embodiments 1-12 and 16-31, wherein the

Bifidobacterium sp. 12 1 47BFAA has a 16S RNA gene that is at least 95% identical to SEQ ID NO:!. 33. The method of any one of embodiments 1-12 and 16-32, wherein the

Bifidobacterium sp. 12 1 47BFAA has a 16S RNA gene that is at least 95% identical to SEQ ID NO:2. 34. The method of any one of embodiments 1-12 and 16-33, wherein the

Bifidobacterium sp. 12 1 47BFAA has a 16S RNA gene that is at least 95% identical to SEQ ID NO:3.

35. The method of any one of embodiments 1-12 and 16-34, wherein the Collinsella sp. 4 847FAA has a 16S RNA gene that is at least 95% identical to SEQ ID NO:4.

36. The method of any one of embodiments 1-12 and 16-35, wherein the

Methanobrevibacter smithii TS96C has a genomic sequence that is at least 95% identical to GCF_000190175.

37. The method of any one of embodiments 1-12 and 16-36, wherein the Oscillibacter sp. ER4 has a 16S RNA gene that is at least 95% identical to SEQ ID NO:5.

38. The method of any one of embodiments 1-12 and 16-37, wherein the bacterial strain in the composition is viable.

39. The method of any one of embodiments 1-12 and 16-38, wherein the bacterial strain is lyophilized. 40. The method of any one of embodiments 1-12 and 16-39, wherein the composition further comprises one or more cryopreservants.

41. The method of any one of embodiments 1-12 and 16-40, wherein the effective amount of the bacterial strain comprises at least about 1 xlO ³ colony forming units (CFU) of the bacterial strain. 42. The method of any one of embodiments 1-12 and 16-41, wherein the effective amount of the bacterial strain comprises about 1 xlO ⁴ to about 1 xlO ¹⁵ CFU of the bacterial strain.

43. The method of any one of embodiments 1-12 and 16-42, wherein the effective amount of the bacterial strain comprises about 1 xlO ⁶ to about 1 xlO ¹⁰ CFU of the bacterial strain.

44. The method of any one of embodiments 1-12 and 16-43, wherein the bacterial strain in the composition is non-viable.

45. The method of embodiment 44, wherein the non-viable bacterial strain is heat- killed, irradiated, or lysed.

46. The method of any one of embodiments 1-12 and 16-45, wherein the method comprises administering the composition to the subject once, twice, or three times per day.

47. The method of any one of embodiments 1-12 and 15-46, wherein the composition is formulated for oral administration.

48. The method of any one of embodiments 1-12 and 15-47, wherein the composition is formulated as a tablet, a capsule, a powder, or a liquid.

49. The method of any one of embodiments 1-12 and 15-48, wherein the composition is formulated as a tablet.

50. The method of embodiment 49, wherein the tablet is coated.

51. The method of embodiment 50, wherein the coating comprises an enteric coating. 52. The method of any one of embodiments 1-12 and 15-46, wherein the composition is formulated for rectal administration. 53. The method of any one of embodiments 1-12 and 15-46, wherein the composition is formulated for intravenous administration.

54. The method of any one of embodiments 1-12 and 15-46, wherein the composition is formulated for intratumoral administration.

55. The method of any one of embodiments 1-54, wherein the method further comprises administering another treatment of cancer and/or other adjunct therapy to the subject. 56. The method of embodiment 55, wherein the composition comprising the bacterial strain treatment and the treatment for cancer and/or adjunct therapy are administered simultaneously.

57. The method of embodiment 55, wherein the composition comprising the bacterial strain treatment and the treatment for cancer and/or adjunct therapy are administered sequentially.

58. The method of any one of embodiments 53-56, wherein the treatment for cancer and/or adjunct therapy comprises a probiotic.

59. The method of any one of embodiments 53-58, wherein the treatment for cancer and/or adjunct therapy comprises surgery, radiation therapy, or a combination thereof. 60. The method of any one of embodiments 53-59, wherein the treatment for cancer and/or adjunct therapy comprises a therapeutic agent.

61. The method of embodiment 60, wherein the therapeutic agent comprises a chemotherapeutic agent, a targeted therapy, an immunotherapy, or a combination thereof.

62. The method of embodiment 61, wherein the chemotherapeutic agent comprises carboplatin, cisplatin, gemcitabine, methotrexate, paclitaxel, pemetrexed, lomustine, temozolomide, dacarbazine, or a combination thereof.

63. The method of embodiment 60 or 61, wherein the targeted therapy comprises afatinib dimaleate, bevacizumab, cetuximab, crizotinib, erlotinib, gefitinib, sorafenib, sunitinib, pazopanib, everolimus, dabrafenib, aldesleukin, interferon alfa-2b, ipilimumab, peginterferon alfa-2b, trametinib, vemurafenib, or a combination thereof.

64. The method of embodiment 61-63, wherein the immunotherapy comprises a cell therapy, a therapy with an immunomodulator, or a combination thereof.

65. The method of embodiment 64, wherein the immunomodulator is an immune checkpoint inhibitor selected from the group consisting of: ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, and a combination thereof.

66. The method of embodiment 64, wherein the immunomodulator is a co-stimulatory immune checkpoint agent selected from the group consisting of: IBIIOI, utomilumab,

MEDI1873, and a combination thereof.

67. The method of any one of embodiments 60-66, wherein the composition comprising the bacterial strain further comprises the therapeutic agent. 68. The method of embodiment 64, wherein the cell therapy is a CAR T-cell therapy

69. The method of any one of embodiments 1-68, wherein the subject is a human. [00277] It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention which is defined by the scope of the appended claims. Other aspects, advantages, and modification are within the scope of the following claims.