Treatment of clostridium difficile infection

Abstract

To provide compositions and methods for the treatment or prevention of pathogenic infections, including those caused by Clostridium difficile.SOLUTION: The present invention provides compositions comprising purified bacterial strains of Flavinofractor plautii, Anaerotruncus colihominis, Eubacterium fissicatena, Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta or Clostridium innocuum.SELECTED DRAWING: None

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 62 / 349,914, filed June 14, 2016, which is incorporated by reference in its entirety.

[0002] The present disclosure relates to compositions of purified strains and methods of treating pathogen infections, such as Clostridium difficile infections, by administering the compositions to a subject having a pathogen infection. [Background technology]

[0003] The collection of commensal microorganisms, including bacteria, viruses and fungi, in and on the human body is collectively known as the human microbiome. The bacterial subset of the human microbiome plays important roles in host nutrient acquisition, development, immunological homeostasis, neurological health and protection from pathogens (LeBlanc et al. Curr. Opin. Biotechnol. (2013) 24(2): 160-168; Hooper et al. Science (2012) 336(6086): 1268-1273; Hughes et al. Am. J. Gastroenterol. (2013) 108(7): 1066-1074). As the largest reservoir of mammalian commensals, bacteria in the gastrointestinal (GI) tract affect nearly all of these aspects of human biology (Blaser J. Clin. Invest. (2014) 124(10): 4162-4165). Thus, perturbation of the normal bacterial population in the GI niche, a state known as dysbiosis, can predispose humans to a variety of diseases.

[0004] Clostridium difficile infection (CDI) occurs following intestinal colonization by the anaerobic, spore-forming, Gram-positive pathogen Clostridium difficile. After colonization of the GI tract, C. difficile produces toxins that cause diarrhea and can ultimately lead to death. The disease is the most frequently identified cause of hospital-acquired diarrhea and is thought to occur as a direct result of dysbiosis (Calfee Geriatrics (2008) 63: 10-21; Shannon-Lowe et al BMJ (2010) 340: c1296). Not surprisingly, the use of almost all classes of antibiotics has been associated with CDI, likely by inducing GI tract dysbiosis, thereby allowing the predominant growth of C. difficile. Due to its natural multidrug resistance and the emergence of fluoroquinolone-resistant strains currently prevalent throughout North America and Europe, the U.S. Centers for Disease Control and Prevention now classifies CDI as a threat to public health that requires a rapid and aggressive response. C. difficile is responsible for approximately 500,000 infections and has been associated with approximately 29,000 deaths in 2011 (Lessa et al. NEJM 2015, 372: 825-834).

[0005] The antibiotics metronidazole, vancomycin and fidaxomicin are current therapeutic options for the treatment of CDI. However, metronidazole is inadequate due to low response rates, and neither metronidazole nor vancomycin prevents disease recurrence, with up to 30 percent of patients who initially respond experiencing clinical recurrence after antibiotic cessation (Miller Expert Opin. Pharmacother. (2010) 11:1569-1578).

[0006] Fidaxomicin has been shown to be superior to vancomycin in preventing recurrent CDI (Mullane Ther. Adv. Chronic Dis. (2014) 5(2): 69-84). Due to its narrow spectrum of activity, fidaxomicin is thought to allow reconstitution of the normal microbiome of the gastrointestinal tract after dysbiosis and CDI, thereby reducing the likelihood of recurrent disease (Tannock et al. Microbiology (2010) 156 (Pt 11): 3354-3359; Louie et al. Clin. Infect. Dis. (2012) 55 Suppl. 2: S132-142). Nevertheless, 14% of fidaxomicin-treated patients experience CDI relapses, and mutations conferring reduced susceptibility have already been reported (Eyre et al. J. Infect. Dis. (2014) 209(9): 1446-1451).

[0007] Because the risk of recurrent CDI is heightened by antibiotic use and C. difficile spores are inherently recalcitrant to the available chemotherapy inventory, alternative therapeutic modalities for the treatment of CDI are being explored. Fecal transplantation (FMT) is one such modality that has shown efficacy against CDI (Khoruts et al. Immunol. Lett. (2014) 162(2): 77-81; van Nood et al. N. Engl. J. Med. (2013) 368(5): 407-415). To date, studies of FMT for the treatment of CDI have reported results of up to 90% cure rates in three randomized controlled trials (Cammarota et al. Alimen. Pharmacol. Therap. (2015) 41(9): 835-843; Kassam et al. Am. J. Gastroenterol. (2013) 108(4): 500-508; van Nood et al. N. Engl. J. Med. (2013) 368(5): 407-415; Youngster et al. Infec. Dis. Soc. Am. (2014) 58(11): 1515-15222).

[0008] Despite the success of FMT, this therapeutic approach is not without risks and logistical concerns. FMT donor selection is critical and difficult. When FMT donor recruitment is performed with rigorous screening and standardized protocols, the majority of potential donors are disqualified from the process. Only 6-10 percent of potential FMT donors are successful, with the majority of disqualifications resulting from asymptomatic GI pathogen carriage (Paramsothy et al. Inflamm. Bowel Dis. (2015) 21(7): 1600-1606; Borody et al. Curr. Opin. Gastroenterol. (2014) 30(10): 97-105; Burns et al. Gastroenterology (2015) 148: S96-S97; Surawicz Ann. Intern. Med. (2015) 162(9): 662-663). Furthermore, donor-to-donor variability can lead to variability in FMT efficacy. In addition, the risk of transmitting non-communicable diseases may even be increased by FMT. Indeed, significant weight gain has been reported in patients undergoing FMT from overweight fecal donors (Alang et al. Open Forum Infect. Dis. (Winter 2015) 2(1)). Summary of the Invention [Problem to be solved by the invention]

[0009] Provided herein are compositions and methods for the treatment or prevention of pathogen infections, including C. difficile. [Means for solving the problem]

[0010] In one aspect, the present disclosure provides Clostridium hathewayi, Blautia hansenii, Blautia producta, Blautia producta ATCC 27340, Clostridium bacterium UC5.1-1D4, Blautia coccoides, Eubacterium contortum, Eubacterium fissicatena, Sellimonas intestinalis, Dracourtella massiliensis, Dracourtella massiliensis GD1, Ruminococcus torques, Anaerostipes caccae, Clostridium scindens, Marvinbryanta formatexigens, Eisenbergiella tayi, Flavinofractor plautii, Clostridium orbiscindens 1_3_50AFAA, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Anaerotruncus colihominis, Anaerotruncus colihominis DSM 17241, Clostridium symbiosum, Clostridium symbiosum WAL-14163, Clostridium bolteae, Clostridium bolteae 90A9, Dorea longicatena, Dorea longicatena CAG:42, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Blautia wexlerae, Clostridium disporicum, Erysipelatoclostridium ramosum, Pseudoflavinofractor capillosus, Turicibacter sanguinis, Lactobacillus mucosae, Ruminococcus obeum, Megasphaera elsdenii, Acidaminococcus fermentans, AcidaminococcusIn one embodiment, a composition is provided that comprises two or more purified strains of a species selected from the group consisting of: Bacteroides cellulosilyticus, Anaerostipes hadrus, Eubacterium rectale, Ruminococcus champanellensis, Ruminococcus albus, Bifidobacterium bifidum, Blautia luti, Roseburia faecis, Fusicatenibacter saccharivorans, Roseburia faecis, Blautia faecis, Dorea formicigenerans, and Bacteroides ovatus.

[0011] In some embodiments of the compositions provided herein, the composition comprises Clostridium hathewayi, Blautia hansenii, Blautia producta, Blautia producta ATCC 27340, Clostridium bacterium UC5.1-1D4, Blautia coccoides, Eubacterium contortum, Eubacterium fissicatena, Sellimonas intestinalis, Dracourtella massiliensis, Dracourtella massiliensis GD1, Ruminococcus torques, Anaerostipes caccae, Clostridium scindens, Marvinbryanta formatexigens, Eisenbergiella tayi, Flavinofractor plautii, Clostridium orbiscindens 1_3_50AFAA, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Anaerotruncus colihominis, Anaerotruncus colihominis DSM 17241, Clostridium symbiosum, Clostridium symbiosum WAL-14163, Clostridium bolteae, Clostridium bolteae 90A9, Dorea longicatena, Dorea longicatena CAG:42, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Blautia wexlerae, Turicibacter sanguinis, Lactobacillus mucosae and Bacteroides ovatus.

[0012] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains of a species selected from the group consisting of Clostridium hathewayi, Blautia hansenii, Blautia producta, Blautia coccoides, Eubacterium contortum, Eubacterium fissicatena, Anaerostipes caccae, Clostridium scindens, Marvinbryanta formatexigens, and Eisenbergiella tayi.

[0013] In some embodiments of the compositions provided herein, the composition comprises Flavinofractor plautii, Clostridium orbiscindens 1_3_50AFAA, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Anaerotruncus colihominis, Anaerotruncus colihominis DSM 17241, Eubacterium fissicatena, Sellimonas intestinalis, Dracourtella massiliensis, Dracourtella massiliensis GD1, Ruminococcus torques, Clostridium symbiosum, Clostridium symbiosum WAL-14163, Clostridium bolteae, Clostridium bolteae 90A9, Dorea longicatena, Dorea longicatena CAG:42, Blautia producta, Blautia producta ATCC 27340, Clostridium bacterium UC5.1-1D4, Clostridium innocuum and Erysipelotrichaceae_bacterium_21-3.

[0014] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Clostridium orbiscindens 1_3_50AFAA, Anaerotruncus colihominis DSM 17241, Dracourtella massiliensis GD1, Clostridium symbiosum WAL-14163, Clostridium bolteae 90A9, Dorea longicatena CAG:42, Clostridium bacterium UC5.1-1D4, and Erysipelotrichaceae_bacterium_21-3.

[0015] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Clostridium orbiscindens 1_3_50AFAA, Anaerotruncus colihominis DSM 17241, Sellimonas intestinalis, Clostridium symbiosum WAL-14163, Clostridium bolteae 90A9, Dorea longicatena CAG:42, Clostridium bacterium UC5.1-1D4, and Erysipelotrichaceae_bacterium_21_3.

[0016] In some embodiments of the compositions provided herein, the compositions comprise purified strains Clostridium orbiscindens 1_3_50AFAA, Anaerotruncus colihominis DSM 17241, Dracourtella massiliensis GD1, Clostridium symbiosum WAL-14163, Clostridium bolteae 90A9, Dorea longicatena CAG:42, Clostridium bacterium UC5.1-1D4, and Erysipelotrichaceae_bacterium_21-3.

[0017] In some embodiments of the compositions provided herein, the compositions comprise purified strains Clostridium orbiscindens 1_3_50AFAA, Anaerotruncus colihominis DSM 17241, Sellimonas intestinalis GD1, Clostridium symbiosum WAL-14163, Clostridium bolteae 90A9, Dorea longicatena CAG:42, Clostridium bacterium UC5.1-1D4, and Erysipelotrichaceae_bacterium_21_3.

[0018] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Flavinofractor plautii, Anaerotruncus colihominis, Dracourtella massiliensis, Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta, and Clostridium innocuum.

[0019] In some embodiments of the compositions provided herein, the compositions comprise purified strains of Flavinofractor plautii, Anaerotruncus colihominis, Dracourtella massiliensis, Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta, and Clostridium innocuum.

[0020] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Flavinofractor plautii, Anaerotruncus colihominis, Eubacterium fissicatena, Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta, and Clostridium innocuum.

[0021] In some embodiments of the compositions provided herein, the compositions comprise purified strains of Flavinofractor plautii, Anaerotruncus colihominis, Eubacterium fissicatena, Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta, and Clostridium innocuum.

[0022] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Flavinofractor plautii, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Anaerotruncus colihominis, Eubacterium fissicatena, Ruminococcus torques, Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, and Bacteroides ovatus.

[0023] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Clostridium orbiscindens 1_3_50AFAA, Anaerotruncus colihominis DSM 17241, Dracourtella massiliensis GD1, Clostridium symbiosum WAL-14163, Clostridium bolteae 90A9, Dorea longicatena CAG:42, Clostridium bacterium UC5.1-1D4, Erysipelotrichaceae_bacterium_21-3, and Bacteroides ovatus.

[0024] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Clostridium orbiscindens 1_3_50AFAA, Anaerotruncus colihominis DSM 17241, Sellimonas intestinalis, Clostridium symbiosum WAL-14163, Clostridium bolteae 90A9, Dorea longicatena CAG:42, Clostridium bacterium UC5.1-1D4, Erysipelotrichaceae_bacterium_21-3, and Bacteroides ovatus.

[0025] In some embodiments of the compositions provided herein, the composition does not include a strain of the species Flavinofractor plautii, Subdoligranulum, or Lachnospiraceae bacterium 7_1_58FAA. In some embodiments of the compositions provided herein, the composition does not include a strain of the species Bacteroides ovatus. The composition of any one of claims 4 to 12, wherein the composition does not include a strain of the species Flavinofractor plautii, Subdoligranulum, Clostridium orbiscindens 1_3_50AFAA, or Lachnospiraceae bacterium 7_1_58FAA.

[0026] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains of a species selected from the group consisting of Clostridium scindens, Clostridium hathewayi, Blautia hansenii, Blautia wexlerae, Blautia producta, Blautia coccoides, Dorea longicatena, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Flavinofractor plautii, Lachnospiraceae bacterium 7-_1_58FAA, Subdoligranulum, Anaerotruncus colihominis, and Clostridium symbiosum. In some embodiments of the compositions provided herein, the compositions do not include strains of the species Flavinofractor plautii, Subdoligranulum, or Lachnospiraceae bacterium 7_1_58FAA.

[0027] In some embodiments of the compositions provided herein, the compositions include two or more purified strains of a species selected from the group consisting of Clostridium scindens, Clostridium hathewayi, Blautia hansenii, Blautia wexlerae, Anaerotruncus colihominis, Dorea longicatena, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Flavinofractor plautii, Lachnospiraceae bacterium 7-_1_58FAA, Subdoligranulum, Turicibacter sanguinis, and Lactobacillus mucosae. In some embodiments of the compositions provided herein, the compositions do not include strains of the species Flavinofractor plautii, Subdoligranulum, or Lachnospiraceae bacterium 7_1_58FAA.

[0028] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Dorea longicatena, Ruminococcus obeum, Megasphaera elsdenii, Acidaminococcus fermentans, Acidaminococcus intestine, Ruminococcus faecis, Bacteroides cellulosilyticus, Anaerostipes hadrus, Flavinofractor plautii, Eubacterium rectale, Ruminococcus champanellensis, Ruminococcus albus, Bifidobacterium bifidum, Ruminococcus faecis, Blautia luti, Roseburia faecis, Fusicatenibacter saccharivorans, Blautia faecis, Dorea formicigenerans, and Blautia hansenii.

[0029] In some embodiments of the compositions provided herein, the composition comprises two or more purified strains of a species selected from the group consisting of Acidaminococcus fermentans, Acidaminococcus intestine, Anaerostipes hadrus, Blautia faecis, Blautia hansenii, Dorea formicigenerans, Dorea longicatena, Eubacterium rectale, Flavinofractor plautii, Fusicatenibacter saccharivorans, Megasphaera elsdenii, Roseburia faecis, Ruminococcus champanellensis, Ruminococcus albus, Ruminococcus faecis, and Ruminococcus obeum.

[0030] In one aspect, the disclosure provides a composition comprising two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159.

[0031] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:1-23, SEQ ID NO:83, and SEQ ID NO:124-159.

[0032] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23.

[0033] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NOs:124-159. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21. In some embodiments of the compositions provided herein, the compositions include a purified strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21. In some embodiments of the compositions provided herein, the compositions include two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments of the compositions provided herein, the compositions include two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157. In some embodiments of the compositions provided herein, the composition comprises a purified strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0034] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21, and the compositions do not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-156, and the compositions do not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:157-159.

[0035] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-145, SEQ ID NO:152-159, SEQ ID NO:18, and SEQ ID NO:22.

[0036] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22, and the compositions do not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-145 and SEQ ID NO:152-156, and the compositions do not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:157-159.

[0037] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10 and SEQ ID NO:14-22. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159, SEQ ID NO:18, and SEQ ID NO:22.

[0038] In some embodiments of the compositions provided herein, the compositions include two or more purified strains, wherein the two or more purified strains include a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 14-22, and the compositions do not include a strain that includes a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO: 10. In some embodiments of the compositions provided herein, the compositions include two or more purified strains, wherein the two or more purified strains include a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 129-156, SEQ ID NO: 18, SEQ ID NO: 22, and the compositions do not include a strain that includes a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 157-159.

[0039] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:83. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159 and SEQ ID NO:83.

[0040] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:83, and the compositions do not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-156 and SEQ ID NO:83, and the compositions do not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:157-159.

[0041] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:83. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159, SEQ ID NO:22, and SEQ ID NO:83.

[0042] In some embodiments of the compositions provided herein, the compositions include two or more purified strains, wherein the two or more purified strains include a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:83, and the compositions do not include a strain that includes a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments of the compositions provided herein, the compositions include two or more purified strains, wherein the two or more purified strains include a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-145, SEQ ID NO:152-156, SEQ ID NO:22, and SEQ ID NO:83, and the compositions do not include a strain that includes a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:157-159.

[0043] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14-22, and SEQ ID NO:83. In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159, SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NO:83.

[0044] In some embodiments of the compositions provided herein, the compositions include two or more purified strains, wherein the two or more purified strains include a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 14-22 and 83, and the compositions do not include a strain that includes a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO: 10. In some embodiments of the compositions provided herein, the compositions include two or more purified strains, wherein the two or more purified strains include a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 124-15, SEQ ID NO: 18, SEQ ID NO: 22 and SEQ ID NO: 83, and the compositions do not include a strain that includes a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 157-159.

[0045] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, and SEQ ID NO:21.

[0046] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:18, and SEQ ID NO:21.

[0047] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:24-79.

[0048] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:24-27, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:76, and SEQ ID NO:77.

[0049] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:21, and SEQ ID NOs:80-82.

[0050] In one aspect, the disclosure provides a composition comprising two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 84-123.

[0051] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:121, and SEQ ID NO:122.

[0052] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:109, and SEQ ID NO:121.

[0053] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, and SEQ ID NO:122.

[0054] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, and SEQ ID NO:122, and the compositions do not include a strain that comprises a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:93.

[0055] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, and SEQ ID NO:122.

[0056] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, and SEQ ID NO:122, and the compositions do not include a strain that comprises a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:93.

[0057] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:106, and SEQ ID NO:122.

[0058] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, and SEQ ID NO:105.

[0059] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, and SEQ ID NO:120.

[0060] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:104, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, and SEQ ID NO:119.

[0061] In some embodiments of the compositions provided herein, the compositions comprise two or more purified strains, wherein the two or more purified strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:86, SEQ ID NO:95, SEQ ID NO:98, SEQ ID NO:110, SEQ ID NO:122, and SEQ ID NO:123.

[0062] In some embodiments of the compositions provided herein, the composition comprises at least one strain from Clostridium cluster XIVa and at least one strain from Clostridium cluster XVII. In some embodiments of the compositions provided herein, the composition comprises at least one strain from Clostridium cluster IV and at least one strain from Clostridium cluster XVII. In some embodiments of the compositions provided herein, the composition comprises at least one strain from Clostridium cluster XIVa, at least one strain from Clostridium cluster IV and at least one strain from Clostridium cluster XVII.

[0063] In some embodiments of the compositions provided herein, the compositions comprise at least one Bacteroides strain. In some embodiments of the compositions provided herein, the compositions do not include Clostridium scindens. In some embodiments provided herein, the compositions comprise at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 purified strains.

[0064] In some embodiments of the compositions provided herein, one or more of the strains are spore-forming bacteria. In some embodiments of the compositions provided herein, one or more of the strains are in spore form. In some embodiments of the compositions provided herein, each of the strains is in spore form. In some embodiments of the compositions provided herein, one or more of the strains is in a vegetative form. In some embodiments of the compositions provided herein, each of the strains is in a vegetative form.

[0065] In some embodiments of the compositions provided herein, the compositions include only obligate anaerobic strains. In some embodiments of the compositions provided herein, the compositions include strains derived from more than one human donor. In some embodiments of the compositions provided herein, one or more of the strains are baiCD-. In some embodiments of the compositions provided herein, each of the strains is baiCD-. In some embodiments of the compositions provided herein, the composition does not mediate 7-alpha-dehydroxylation of bile acids. In some embodiments of the compositions provided herein, the composition inhibits C. difficile toxin production. In some embodiments of the compositions provided herein, the composition inhibits C. difficile replication and / or survival.

[0066] In some embodiments of the compositions provided herein, the strain is lyophilized. In some embodiments of the compositions provided herein, the compositions induce the proliferation and / or accumulation of regulatory T cells (Tregs).

[0067] In one aspect, the disclosure provides a composition comprising two or more purified strains, the composition comprising at least one strain from Clostridium cluster XIVa and at least one strain from Clostridium cluster XVII. In one aspect, the disclosure provides a composition comprising two or more purified strains, the composition comprising at least one strain from Clostridium cluster IV and at least one strain from Clostridium cluster XVII. In one aspect, the disclosure provides a composition comprising two or more purified strains, the composition comprising at least one strain from Clostridium cluster IV, at least one strain from Clostridium cluster XIVa, and at least one strain from Clostridium cluster XVII.

[0068] In some embodiments of the compositions provided herein, the compositions comprise at least one Bacteroides strain. In some embodiments of the compositions provided herein, the compositions do not include Clostridium scindens. In some embodiments of the compositions provided herein, the composition comprises at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 purified strains.

[0069] In some embodiments of the compositions provided herein, one or more of the strains are spore-forming bacteria. In some embodiments of the compositions provided herein, one or more of the strains are in spore form. In some embodiments of the compositions provided herein, each of the strains is in spore form. In some embodiments of the compositions provided herein, one or more of the strains is in a vegetative form. In some embodiments of the compositions provided herein, each of the strains is in a vegetative form.

[0070] In some embodiments of the compositions provided herein, the composition comprises only obligate anaerobic strains. In some embodiments of the compositions provided herein, the compositions contain strains derived from more than one human donor.

[0071] In some embodiments of the compositions provided herein, one or more of the strains are baiCD-. In some embodiments of the compositions provided herein, each of the strains is baiCD-. In some embodiments of the compositions provided herein, the composition does not mediate 7-alpha-dehydroxylation of bile acids. In some embodiments of the compositions provided herein, the composition inhibits C. difficile toxin production. In some embodiments of the compositions provided herein, the composition inhibits C. difficile replication and / or survival.

[0072] In some embodiments of the compositions provided herein, the strain is lyophilized. In some embodiments of the compositions provided herein, the compositions induce the proliferation and / or accumulation of regulatory T cells (Tregs).

[0073] In one aspect, the disclosure provides a pharmaceutical composition comprising any of the compositions provided herein, further comprising a pharmacologically acceptable excipient. In some aspects of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for oral delivery. In some aspects of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for rectal delivery. In some aspects of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for enteral delivery. In some aspects of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for colonic delivery. In one aspect, the disclosure provides a food product comprising any of the compositions provided herein, further comprising nutrients.

[0074] In one aspect, the disclosure provides a method of treating a pathogen infection in a subject comprising administering to the subject a therapeutically effective amount of any of the compositions or food products provided herein to treat the pathogen infection.

[0075] In some embodiments of the methods provided herein, the pathogen infection is C. difficile, vancomycin-resistant Enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), Neisseria gonorrhea, multidrug-resistant Acinetobacter, Campylobacter, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa, Salmonella, drug-resistant nontyphoidal Salmonella, drug-resistant Salmonella Typhi, drug-resistant Shigella, methicillin-resistant Staphylococcus aureus, drug-resistant Streptococcus pneumoniae, drug-resistant tuberculosis, vancomycin-resistant Staphylococcus aureus, erythromycin-resistant Group A Streptococcus, clindamycin-resistant Group B Streptococcus, and combinations thereof. In some embodiments of the methods provided herein, the pathogen infection is C. difficile. In some embodiments of the methods provided herein, the pathogen infection is vancomycin-resistant Enterococci.

[0076] In some embodiments of the methods provided herein, the subject is a human. In some embodiments of the methods provided herein, the subject is an asymptomatic carrier. In some embodiments of the methods provided herein, the subject is administered one dose of an antibiotic prior to administration of the composition. In some embodiments of the methods provided herein, the subject is administered more than one dose of an antibiotic prior to administration of the composition. In some embodiments of the methods provided herein, the subject is not administered an antibiotic prior to administration of the composition.

[0077] In some embodiments of the methods provided herein, the composition is administered to the subject by oral administration. In some embodiments of the methods provided herein, the composition is administered to the subject by rectal administration. In some embodiments of the methods provided herein, the administration results in the expansion and / or accumulation of regulatory T cells (Tregs).

[0078] Each of the limitations of the present invention may encompass various aspects of the present invention. Thus, each of the limitations of the present invention involving any one element or combination of elements is anticipated to be encompassed in each aspect of the present invention. The present invention is not limited in its application to the details of the construction and organization of components set forth in the following description or illustrated in the drawings. The present invention can be implemented or carried out in other embodiments and in various ways.

[0079] The accompanying drawings are not intended to be drawn to scale. The figures are illustrative only and are not required for enablement of the disclosure. For clarity, every component may not be labeled in every drawing. In the drawings: [Brief description of the drawings]

[0080] [Figure 1] FIG. 1 shows the strains of compositions A-D. Each entry includes the SEQ ID NO of the strain's 16S rDNA sequence, the strain identifier, and the species with the closest known homology (which may be more than one species). Roman numerals in parentheses indicate the Clostridium cluster classification of each strain based on the closest species homology. Strains not classified in cluster XIVa are highlighted in bold. Two non-Clostridium strains (the closest known species Turicibacter sanguinis of SEQ ID NO:2, and the closest known species Lactobacillus mucosae of SEQ ID NO:6) do not belong to the Clostridium genus. [Diagram 2]FIG. 2 shows various Clostridium difficile infection models. The timeline indicates the type of antibiotic, duration of treatment, and exposure to C. difficile spores. The top panel shows an antibiotic cocktail treatment model where antibiotic cocktail is provided in the drinking water from day -10 to day -3, followed by clindamycin intraperitoneally on day -1. The middle panel shows a clindamycin IP injection model where clindamycin is administered by intraperitoneal injection on day -1. The bottom panel shows a cefoperazone treatment model where cefoperazone is provided in the drinking water from day -12 to day -2, followed by administration of a live biotherapeutic drug (LBP) on day -1. [Diagram 3] Figure 3 shows the conditions of the experiment described in Example 1. Groups of mice were divided based on the antibiotic regimen they received prior to administration of the indicated amount of C. difficile spores. "Abx" refers to treatment with any of the antibiotic regimens.

[0081] [Figure 4A-4L] Figures 4A to 4L show data obtained in Example 1. Figures 4A to 4D show survival of mice receiving no treatment (Figure 4A), antibiotic cocktail (Figure 4B), clindamycin (Figure 4C) or cefoperazone (Figure 4D) prior to C. difficile infection. Figures 4E to 4H show body weights of mice receiving no treatment (Figure 4E), antibiotic cocktail (Figure 4F), clindamycin (Figure 4G) or cefoperazone (Figure 4H) prior to C. difficile infection. Figures 4I to 4L show C. difficile load (CFU) per gram of feces from mice receiving no treatment (Figure 4I), antibiotic cocktail (Figure 4J), clindamycin (Figure 4K) or cefoperazone (Figure 4L) prior to C. difficile infection. Open circles indicate infection with 10 C. difficile spores and closed squares indicate infection with 10,000 C. difficile spores. The filled triangles in Figure 4J indicate an additional experimental arm in which mice were treated with vancomycin after C. difficile infection. [Diagram 5]Figure 5 shows the experimental conditions evaluated in Example 2, and the results are shown in Figures 7 to 9. Composition E corresponds to a mixture of 17 strains (see, e.g., Narushima et al., Gut Microbes 5: 3, 333-339). Composition I corresponds to a mixture of Clostridium scindens, Pseudoflavonifractor capillosus, and Blautia hansenii. "Abx" refers to treatment with any of the antibiotic regimens. [Figure 6] Figure 6 shows mouse survival over time following infection with C. difficile spores in the experimental conditions shown in Figure 5. Mice that lost >20% of baseline body weight were included in the mortality count of the survival curves.

[0082] [Figures 7A-7I] Figures 7A through 7I show the weights of mice at various times after infection with C. difficile spores. Groups of mice received cefoperazone treatment (Abx) followed by the indicated compositions, or no cefoperazone (no Abx) and then were administered C. difficile spores. Figure 7A shows the weights of mice that received no antibiotic treatment. Figure 7B shows the weights of mice that received cefoperazone treatment. Figure 7C shows the weights of mice that received cefoperazone followed by vancomycin treatment. Figure 7D shows the weights of mice that received cefoperazone followed by Composition I treatment. Figure 7E shows the weights of mice that received cefoperazone followed by Composition E treatment. Figure 7F shows the weights of mice that received cefoperazone followed by Composition A treatment. Figure 7G shows the weights of mice that received cefoperazone followed by Composition B treatment. Figure 7H shows the weights of mice that received cefoperazone followed by Composition C treatment. FIG. 7I shows the weight of mice receiving cefoperazone followed by Composition D treatment. [Figure 8A-8C]Figures 8A through 8C show the amount of C. difficile in fecal pellets by colony forming units (CFU) at various times after infection with C. difficile. Figure 8A shows the C. difficile CFU / g feces at 1 day post-infection. Figure 8B shows the C. difficile CFU / g feces at 3 days post-infection. Figure 8C shows the C. difficile CFU / g feces at 8 days post-infection. [Figure 9] FIG. 9 shows the conditions of the experiment evaluated in Example 3, and the results are shown in FIGS.

[0083] [Figure 10] Figure 10 shows mouse survival over time following infection with C. difficile spores in the experimental conditions shown in Figure 9. Mice that lost >20% of baseline body weight were included in the mortality count of the survival curves. [Figure 11] FIG. 11 shows the body weight of mice at various times after infection with C. difficile spores. [Figure 12] FIG. 12 shows the C. difficile burden in fecal pellets by colony forming units (CFU) recovered from mice 1, 3 and 8 days after infection with C. difficile. [Figure 13] Figure 13 shows the strains of Composition F. The genus-species designation indicates the closest species based on the sequence of the isolated strain.

[0084] [Figure 14] FIG. 14 shows the classification of the strains in composition F according to the Clostridium cluster and their ability to produce short chain fatty acids. [Figure 15] Figure 15 shows the experimental conditions evaluated in Example 4, the results of which are shown in Figures 16 to 18. Dose days are relative to infection with C. difficile. FMT refers to fecal transplantation with feces isolated from mice or from humans. [Figure 16]Figure 16 shows mouse survival over time following infection with C. difficile spores in the experimental conditions shown in Figure 15. Mice that lost >20% of baseline body weight were included in the mortality count of the survival curves.

[0085] [Fig. 17A-17H] Figures 17A through 17H show the weights of mice at various times after infection with C. difficile spores. Groups of mice received cefoperazone (Abx), the compositions shown below, and then were administered C. difficile spores. Figure 17A shows the weights of mice that received cefoperazone. Figure 17B shows the weights of mice that received cefoperazone treatment followed by FMT with fecal material from a human. Figure 17C shows the weights of mice that received cefoperazone treatment followed by FMT with fecal material from a mouse. Figure 17D shows the weights of mice that received cefoperazone treatment followed by Composition B on day -1. Figure 17E shows the weights of mice that received cefoperazone treatment followed by Composition B on days -2 and -1. Figure 17F shows the weights of mice that received cefoperazone treatment followed by Composition B on days -2, -1, 1, 2, and 3. Figure 17G shows the weights of mice receiving cefoperazone treatment followed by Composition F on day -1. Figure 17H ​​shows the weights of mice receiving cefoperazone treatment followed by Composition F on days -2, -1, 1, 2 and 3. [Figure 18A-18B] Figures 18A to 18B show the content of C. difficile in fecal pellets by colony forming units (CFU) at various times after infection with C. difficile. Figure 18A shows the C. difficile CFU / g feces at 8 days post-infection. Figure 18B shows the C. difficile CFU / g feces at 17 days post-infection. [Figure 19] Figure 19 shows the strains of Composition G. The genus-species designation indicates the closest species based on the sequence of the isolated strain.

[0086] [Figure 20]Figure 20 shows the experimental conditions evaluated in Example 5 and the results are shown in Figures 21 to 23. Composition B1 = composition B with Bacteroides, composition B2 = composition B with Bacteroides without Flavonifractor plautii. [Figure 21] Figure 21 shows mouse survival over time following infection with C. difficile spores in the experimental conditions shown in Figure 20. Mice that lost >20% of baseline body weight were included in the mortality count of the survival curves. [Fig. 22A-22J] Figures 22A to 22J show the weights of mice at various times after infection with C. difficile spores. Figure 22A shows the weights of mice receiving vehicle control. Figure 22B shows the weights of mice receiving composition F. Figure 22C shows the weights of mice receiving composition G. Figure 22D shows the weights of mice receiving cefoperazone treatment followed by composition B. Figure 22E shows the weights of mice receiving cefoperazone treatment followed by composition B2 (= composition B supplemented with Bacteroides without Flavonifractor plautii). Figure 22F shows the weights of mice receiving cefoperazone treatment followed by composition B1 (= composition B supplemented with Bacteroides). Figure 22G shows the weights of mice receiving cefoperazone treatment followed by frozen composition B. Figure 22H shows the weights of mice receiving cefoperazone treatment followed by ethanol-treated human fecal samples. Figure 22I shows the weight of mice receiving cefoperazone treatment followed by ethanol treatment with Composition B. Figure 22J shows the weight of mice receiving cefoperazone treatment followed by Composition J.

[0087] [Diagram 23] FIG. 23 shows the C. difficile load in fecal pellets by colony forming units (CFU) at various times after infection with C. difficile. [Figure 24] FIG. 24 shows the weights of the indicated groups of mice at various times after infection with C. difficile spores. [Diagram 25] FIG. 25 shows the conditions of the experiment evaluated in Example 6, and the results are shown in FIGS. [Figure 26] FIG. 26 shows the strains in composition H (SEQ ID NO: 14 - VE202-13 - Anaerotruncus colihominis (Cluster IV), SEQ ID NO: 16 - VE202-16 - Clostridium symbiosum (Cluster XIVa), SEQ ID NO: 21 - 189 - Clostridium innocuum (Cluster XVII), SEQ ID NO: 82 - PE9 - Clostridium disporicum (Cluster I), SEQ ID NO: 81 - PE5 - Clostridium bolteae (Cluster XIVa), SEQ ID NO: 80 - VE202-18 - Erysipelatoclostridium ramosum (Cluster XVIII).

[0088] [Figure 27A-27B] Figures 27A and 27B show mouse survival and weight loss over time following infection with C. difficile spores according to the experimental conditions shown in Figure 25. Mice that lost >20% of baseline body weight were included in the mortality counts of the survival curves. Figure 29A shows survival / mortality rates for mice receiving the indicated treatments prior to C. difficile infection. Figure 29B shows weight over time for mice receiving the indicated treatments prior to C. difficile infection. [Fig. 28A-28B] Figures 28A and 28B show results from the experimental conditions shown in Figure 25. Figure 28A shows survival / mortality of mice receiving the indicated treatments prior to C. difficile infection. Figure 28B shows weight over time of mice receiving the indicated treatments prior to C. difficile infection. [Figure 29A-29B] Figures 29A and 29B show C. difficile load by CFU per gram of feces collected from mice receiving the indicated treatments prior to C. difficile infection. Figure 29A shows C. difficile load 1 day after C. difficile infection. Figure 29B shows C. difficile load 4 days after C. difficile infection. Figure 29C shows C. difficile load 19 days after C. difficile infection.

[0089] [Diagram 30] Figure 30 shows that Composition B reduced the amount of C. difficile B toxin compared to the untreated controls "2-1(Cdiff)" and "2-4(Cdiff)" and FMT. In addition, Composition B reduced the amount of C. difficile B toxin compared to Composition B supplemented with spores. [Diagram 31] 31 shows that Composition B reduced the growth of C. difficile in an in vitro competition experiment. Cultures of C. difficile were incubated in the presence of B. thetaiotaomicron, C. bifermentans, or Composition B, or in the absence of competitor strain(s) (C. diff only). The amount of C. difficile is shown as a percentage of the control (C. diff only). [Diagram 32] FIG. 32 shows that inoculation with Composition B induced a higher percentage of FoxP3+CD4+ cells (regulatory T cells) in the intestine of germ-free mice compared to control mice ("GF"). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0090] Disclosed herein are compositions comprising the purified strains, as well as pharmaceutical compositions and food products containing such compositions and strains. Also disclosed are methods of treating a pathogen infection, such as a Clostridium difficile (C. difficile) infection, in a subject by administering the compositions to the subject.

[0091] Various factors, including antibiotic use, can induce dysbiosis in the gastrointestinal tract, thereby creating a space for colonization by pathogenic microorganisms, such as C. difficile. Such colonization or pathogen infection can result in a variety of adverse effects on the subject, including diarrhea, which is one of the primary symptoms specific to C. difficile infection (CDI). In the case of CDI, diarrhea is believed to be the result of C. difficile production of B toxin (also called cytotoxin TcdB), which leads to opening of tight junctions between intestinal epithelial cells, increasing vascular permeability, bleeding, and inflammation.

[0092] The compositions described herein are effective for treating C.difficile infection. As shown herein, the disclosed compositions are effective for suppressing the pathogenic effects of C.difficile infection. The compositions provided herein reduce the amount of C.difficile after infection, thereby providing an effective method for removing C.difficile from the body (e.g., the gastrointestinal tract). The compositions provided herein, for example, when administered to a subject, induce the proliferation and / or accumulation of regulatory T cells (Tregs). Surprisingly, it has been found that the compositions disclosed herein reduce or inhibit the production or activity of B toxin of C.difficile, thereby making them effective compositions for treating or preventing CDI. It has also been found that the compositions disclosed herein inhibit the proliferation and / or survival of C.difficile.

[0093] The present disclosure provides compositions comprising purified strains that can be administered to subjects experiencing or having experienced a pathogen infection to treat the infection. In some embodiments, the compositions can be administered to subjects who may be at risk for a pathogen infection. Such subjects include subjects who have previously suffered from a pathogen infection, subjects who have been treated with antibiotics, and subjects about to undergo treatment (e.g., surgery and / or hospitalization) that poses a high risk of pathogen infection. In some embodiments, the pathogen infection is an infection caused by a pathogen that is primarily present in the digestive tract or intestine. In some embodiments, the pathogen that is primarily present in the digestive tract or intestine is Clostridium difficile.

[0094] In some embodiments, one or more of the strains of the compositions provided herein colonize or recolonize the intestinal tract or a portion of the intestinal tract (e.g., colon or cecum) of a subject. Such colonization or recolonization may also be referred to as grafting. In some embodiments, one or more of the strains in the composition recolonize the intestinal tract (e.g., colon or cecum) of a subject after the naturally occurring microbiome has been partially or completely removed, for example, due to the administration of antibiotics. In some embodiments, one or more of the strains in the composition colonize the dysbiotic digestive tract.

[0095] In some embodiments, one or more of the strains of the composition can "outgrow" a pathogen such as C. difficile. That is, in some embodiments, when both a pathogen such as C. difficile and one or more of the bacteria of the compositions provided herein are present in the intestinal tract (e.g., colon or cecum), one or more of the bacteria of the compositions provided herein grow faster (e.g., with a shorter doubling time) than the pathogen, thereby preventing the pathogen from accumulating in the intestinal tract (e.g., colon or cecum). In some embodiments, one or more of the bacteria of the compositions provided herein grow faster because they are better at grafting in the intestinal tract (e.g., colon or cecum). In some embodiments, one or more of the bacteria of the compositions provided herein grow faster because they are better at metabolizing nutrients present in the intestinal tract (e.g., colon or cecum). In some embodiments, the compositions of the strains provided herein prevent or inhibit the production of bacterial toxins by pathogen infections, or prevent or inhibit the cytopathic or cytotoxic effects of such bacterial toxins. In some embodiments, the strains of the compositions provided herein can treat pathogen infections due to the synergy between the strains. Thus, without being limited thereto, in some embodiments, the combination of strains of the compositions provided herein acts synergistically because the combination of strains is particularly suitable for nutrient utilization in the intestinal tract (e.g., colon or cecum), or because the combination is superior in grafting (e.g., by providing a favorable microenvironment), for example, through metabolic interactions and / or.

[0096] In some embodiments, the strain combinations of the compositions provided herein are superior in nutrient utilization compared to pathogens such as C. difficile, thereby inhibiting the growth of pathogens such as C. difficile, and thus treat pathogen infections such as C. difficile. In some embodiments, the strain combinations of the compositions provided herein are superior in grafting compared to pathogens such as C. difficile, thereby inhibiting the growth of pathogens such as C. difficile, and thus treat pathogen infections such as C. difficile. In some embodiments, the strain combinations of the compositions provided herein are superior in nutrient utilization and grafting compared to pathogens such as C. difficile, thereby inhibiting the growth of pathogens such as C. difficile, and thus treat pathogen infections such as C. difficile. In some embodiments, the strain combinations of the compositions provided herein inhibit the growth and / or survival of pathogens such as C. difficile, and thus treat pathogen infections such as C. difficile. In some embodiments, the combination of strains of the compositions provided herein treats pathogen infections such as C. difficile by inducing regulatory T cells (Tregs) in a subject, which results in the reduction or elimination of the pathogen, such as C. difficile. In some embodiments, the combination of strains of the compositions provided herein treats pathogen infections such as C. difficile by inducing regulatory T cells (Tregs) in a subject, which inhibits the proliferation and / or survival of the pathogen, which results in the reduction or elimination of the pathogen, such as C. difficile.

[0097] In some embodiments, synergistic effects are provided by the ability of the combination to colonize a particular niche of the intestinal tract (e.g., the colon or cecum). In some embodiments, synergistic effects are provided by the ability of the combination to metabolize a particular nutrient. In some embodiments, synergistic effects are provided by the ability of the combination to provide a particular metabolic product into the environment. Such a particular metabolic product can inhibit the growth of pathogens and / or stimulate the growth of non-pathogens. In some embodiments, synergistic effects are provided by the ability of the combination to provide a short chain fatty acid into the environment. In some embodiments, synergistic effects are provided by the ability of the combination to provide a particular short chain fatty acid into the environment. In some embodiments, synergistic effects are provided by the ability of the combination to produce butyrate. In some embodiments, synergistic effects are provided by the ability of the combination to produce acetate. In some embodiments, synergistic effects are provided by the ability of the combination to produce lactate. In some embodiments, synergistic effects are provided by the ability of the combination to produce propionate. In some aspects, the ability of the combination to produce succinate provides a synergistic effect. In some aspects, the ability of the combination to produce multiple metabolic products provides a synergistic effect. In some aspects, the ability of the combination to produce multiple short chain fatty acids provides a synergistic effect. In some aspects, the ability of the combination to produce both butyrate and acetate provides a synergistic effect. In some aspects, the ability of the combination to produce both butyrate and lactate provides a synergistic effect. In some aspects, the ability of the combination to produce both butyrate and propionate provides a synergistic effect. In some aspects, the ability of the combination to produce both butyrate and succinate provides a synergistic effect. In some aspects, the ability of the combination to produce butyrate, acetate, and an additional short chain fatty acid provides a synergistic effect.

[0098] The strains used in the compositions provided herein are generally isolated from the microbiome of a healthy individual. In some aspects, the compositions include strains from a single individual. In some aspects, the compositions include strains from multiple individuals. In some aspects, the strains are obtained, isolated, and grown individually from multiple individuals. The individually grown bacterial compositions can then be combined to provide the compositions of the present disclosure. It should be understood that the origin of the strains in the compositions provided herein is not limited to human microbiomes from healthy individuals. In some aspects, the strains are derived from humans with dysbiotic microbiomes. In some aspects, the strains are derived from non-human animals or environments (e.g., soil or surface water). In some aspects, the combinations of strains provided herein are derived from multiple sources (e.g., humans and non-human animals).

[0099] In some embodiments, the bacteria of the compositions provided herein are anaerobic bacteria. In some embodiments, the bacteria of the compositions provided herein are obligate anaerobic bacteria. In some embodiments, the bacteria of the compositions provided herein are Clostridium bacteria. Clostridium bacteria can be classified into phylogenetic clusters with other closely related strains and species. (See, for example, Rajilic-Stojanovic, M., and de Vos, WM FEMS Microbiol Rev 38, (2014) 996-1047). Generally, Clostridium are classified as belonging to a particular cluster based on the nucleic acid sequence of their 16S rRNA (or 16S rDNA). Methods for identifying specific bacterial species based on their 16S rRNA (or 16S rDNA) nucleic acid sequences are well known in the art (see, e.g., Jumpstart Consortium Human Microbiome Project Data Generation Working, G. PLoS One (2012) 7, e39315).

[0100] Provided herein are compositions comprising strains belonging to specific Clostridium clusters that have been found to be effective in treating and / or preventing pathogen infections (e.g., C. difficile infections). In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IV. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XIVa.

[0101] In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XVII. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster I. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IX. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XIVa and at least one of the strains belongs to Clostridium cluster XVII. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IV, at least one of the strains belongs to Clostridium cluster XIVa and at least one of the strains belongs to Clostridium cluster XVII. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IV, at least one of the strains belongs to Clostridium cluster XIVa and at least one of the strains belongs to Clostridium cluster XVII.

[0102] In some embodiments, the composition has at least two times as many strains belonging to Clostridium cluster XIVa as compared to strains belonging to Clostridium cluster IV. In some embodiments, at least two of the strains of the composition are Clostridium cluster IV and at least five of the strains are Clostridium cluster XIVa. In some embodiments, the composition has at least two times as many strains belonging to Clostridium cluster XIVa as compared to strains belonging to Clostridium cluster IV and the composition has at least one strain belonging to Clostridium cluster XVII. In some embodiments, at least two of the strains of the composition are Clostridium cluster IV and at least five of the strains are Clostridium cluster XIVa and at least one of the strains belongs to Clostridium cluster XVII.

[0103] In some aspects, the compositions provided herein do not include strains belonging to Clostridium cluster XVIII. In some aspects, the compositions provided herein do not include strains belonging to Clostridium cluster XVI. In some aspects, the compositions provided herein do not include strains belonging to Clostridium cluster XI. In some aspects, the compositions provided herein do not include strains belonging to Clostridium cluster I.

[0104] In one aspect, the present disclosure provides a strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159. It should be understood that SEQ ID NOs: 1-83 and 124-159 can encompass both full-length and partial 16S rDNA sequences.

[0105] In one aspect, the disclosure provides a composition comprising a strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159. In one aspect, the disclosure provides a composition comprising a strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159 as an active ingredient. It should be understood that in all compositions provided herein, in some embodiments, the strain(s) is the active ingredient of the composition.

[0106] It should be understood that in all compositions provided herein, in some embodiments, the strains are purified. Thus, for example, the disclosure provides purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159. Additionally, for example, the disclosure provides compositions comprising purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159. The strains disclosed herein may be obtained and purified, in principle, from the microbiota of one or more human individuals, or may be obtained from sources other than human microbiota, such as soil and non-human microbiota. As provided herein, in some embodiments, bacteria isolated from human microbiota, non-human microbiota, soil, or any other alternative source are purified prior to use in the compositions and methods provided herein.

[0107] In one aspect, the disclosure provides a composition comprising one or more bacterial strains, the one or more strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159. In one aspect, the disclosure provides a composition comprising one or more bacterial strains, the one or more strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159. As noted above, in some embodiments, the strains are purified. Thus, in one aspect, the disclosure provides a composition comprising one or more purified strains, the one or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159.

[0108] In one aspect, the disclosure provides a composition comprising two or more purified strains, the two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159. As noted above, in some embodiments, the strains are active ingredients of the composition. Thus, in some embodiments, the disclosure provides a composition comprising two or more purified strains as an active ingredient, the two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-83 and 124-159.

[0109] In one aspect, the disclosure provides strains and strain combinations that are homologous or have a high percentage of homology with strains comprising 16S rDNA sequences selected from the group consisting of SEQ ID NOs: 1-83 and 124-159. As described above, in some embodiments, the strains are purified. Strains comprising 16S rDNA sequences comprising nucleic acid sequences selected from the group consisting of SEQ ID NOs: 1-83 and 124-159 described herein have a high percentage of homology (e.g., greater than 90 percent) with 16S rDNA sequences of strains described in various databases (e.g., National Center for Biotechnology Information). Tables 1 and 3 show the known species with the closest homology when comparing 16S rDNA sequences comprising SEQ ID NOs: 1-83 and 124-159 with 16S rDNA sequences of bacterial species available in public databases. For example, the strain comprising the 16S rDNA sequence of SEQ ID NO:1 disclosed herein (also referred to herein as "strain 71") has the highest homology to a strain of the species Blautia wexlerae defined by accession number NR_044054 (having the 16S rDNA sequence of SEQ ID NO:94). The strain of SEQ ID NO:1 has homology to other published strains as well, but is most closely related to a strain of the species Blautia wexlerae defined by accession number NR_044054. In this specific example, SEQ ID NO:1 has 96.6% homology to SEQ ID NO:94 (corresponding to Blautia wexlerae). It should be understood that multiple strains disclosed herein may have the highest homology to the same species (e.g., SEQ ID NO:4 and SEQ ID NO:5 both have the highest homology to the 16S rDNA sequence of a strain of the species Blautia hansenii).

[0110] It should further be understood that the strains having the 16S rDNA sequences of the nucleic acid sequences selected from the group consisting of SEQ ID NOs: 1-83 and 124-159 disclosed herein also have homologies to other strains based on their entire genome sequences or subsets of their entire genome sequences. The homologies based on the entire genome analysis are shown in Tables 2 and 3.

[0111] 1つえなんですかですがしてがしたすかはすがすかすしははすははすはすはははははなきしすははははすははすはすははすははすはははすはすははすははははすすはtorques、Anaerostipes caccae、Clostridium scindens、Marvinbryanta formatexigens、Eisenbergiella tayi、Flavinofractor plautii、Clostridium orbiscindens 1_3_50AFAA、Lachnospiraceae bacterium 7_1_58FAA、Subdoligranulum、Anaerotruncus colihominis、Anaerotruncus colihominis DSM 17241、Clostridium symbiosum、Clostridium symbiosum WAL-14163、Clostridium bolteae, Clostrdium bolteae 90A9, Dorea longicatena, Dorea longicatena CAG:42, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Blautia wexlerae, Clostridium disporicum, Erysipelatoclostridium ramosum, Pseudoflavinofractor capillosus, Turicibacter sanguinis, Lactobacillus mucosae, Ruminococcus obeum, Megasphaera elsdenii, Acidaminococcusfermentans, Acidaminococcus intestine, Ruminococcus faecis, Bacteroides cellulosilyticus, Anaerostipes hadrus, Eubacterium rectale, Ruminococcus champanellensis, Ruminococcus albus, Bifidobacterium bifidum, Blautia luti, Roseburia faecis, Fusicatenibacter saccharivorans, Roseburia faecis, Blautia faecis, Dorea formicigenerans and Bacteroides ovatus.

[0112] In some cases, this disclosure provides a composition containing 2 or more bacteria strains, 2 or more bacteria strains, Clostridium hathewayi, Blautia hansenii, Blautia producta, Blautia producta ATCC 27340, Clostridium bacterium UC5.1-1D4, Blautia coccoides, Eubacterium contortum, Eubacterium fissicatena, Salmonella intestinalis, Dracourtella massiliensis, Dracourtella massiliensis GD1, Ruminococcus torques、Anaerostipes caccae、Clostridium scindens、Marvinbryanta formatexigens、Eisenbergiella tayi、Flavinofractor plautii、Clostridium orbiscindens 1_3_50AFAA、Lachnospiraceae bacterium 7_1_58FAA、Subdoligranulum、Anaerotruncus colihominis、Anaerotruncus colihominis DSM 17241、Clostridium symbiosum、Clostridium symbiosum WAL-14163、Clostridium bolteae, Clostrdium bolteae 90A9, Dorea longicatena, Dorea longicatena CAG:42, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Blautia wexlerae, Clostridium disporicum, Erysipelatoclostridium ramosum, Pseudoflavinofractor capillosus, Turicibacter sanguinis, Lactobacillus mucosae, Ruminococcus obeum, Megasphaera elsdenii, AcidaminococcusFermentans, Acidaminococcus intestine, Ruminococcus faecis, Bacteroides cellulosilyticus, Anaerostipes hadrus, Eubacterium rectale, Ruminococcus champanellensis, Ruminococcus albus, Bifidobacterium bifidum, Blautia luti, Roseburia faecis, Fusicatenibacter saccharivorans, Roseburia faecis, Blautia faecis, Dorea formicigenerans and Bacteroides ovatus.

[0113] It should be understood that a composition may include multiple strains of a particular species, i.e., for purposes of illustration, a non-limiting example of a composition disclosed herein includes one strain of Clostridium hathewayi and two strains of Blautia hansenii.

[0114] The present invention also includes Clostridium hathewayi, Blautia hansenii, Blautia producta, Blautia producta ATCC 27340, Clostridia bacteria UC5.1-1D4, Blautia coccoides, Eubacterium contortum, Eubacterium fissicatena, Sellimona intestinalis, Dracourtella massiliensis, Dracourtella massiliensis GD1, Ruminococcus torques, Anaerostipes caccae, Clostridium scindens, Marvinbryanta formatexigens, Eisenbergiella tayi, Flavinofractor plautii, Clostridium orbiscindens 1_3_50AFAA, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Anaerotruncus colihominis, Anaerotruncus colihominis DSM 17241, Clostridium symbiosum, Clostridium symbiosum WAL-14163, Clostridium bolteae, Clostrdium bolteae 90A9, Dorea longicatena, Dorea longicatena CAG:42, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Blautia wexlerae, Clostridium disporicum, Erysipelatoclostridium ramosum, Pseudoflavinofractor capillosus, Turicibacter sanguinis, Lactobacillus mucosae, Ruminococcus obeum, Megasphaera elsdenii, Acidaminococcus fermentans, Acidaminococcus intestine, RuminococcusThe present disclosure also encompasses compositions comprising strains highly homologous to and / or encompassed within the species of Bacteroides faecis, Bacteroides cellulosilyticus, Anaerostipes hadrus, Eubacterium rectale, Ruminococcus champanellensis, Ruminococcus albus, Bifidobacterium bifidum, Blautia luti, Roseburia faecis, Fusicatenibacter saccharivorans, Roseburiafaecis, Blautia faecis, Dorea formicigenerans, and Bacteroides ovatus. Thus, in one embodiment, the compositions of the present disclosure include one or more strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 84-123. In some aspects, compositions of the present disclosure include two or more strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 84-123.

[0115] In one aspect, the compositions of the disclosure include two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-23 and 124-159. In some embodiments, the compositions of the present disclosure contain Clostridium hathewayi, Blautia hansenii, Blautia producta, Blautia producta ATCC 27340, Clostridia bacteria UC5.1-1D4, Blautia coccoides, Eubacterium contortum, Eubacterium fissicatena, Sellimona intestinalis, Dracourtella massiliensis, Dracourtella massiliensis GD1, Ruminococcus torques, Anaerostipes caccae, Clostridium scindens, Marvinbryanta formatexigens, Eisenbergiella tayi, Flavinofractor plautii, Clostridium orbiscindens 1_3_50AFAA, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Anaerotruncus colihominis, Anaerotruncus colihominis DSM 17241, Clostridium symbiosum, Clostridium symbiosum WAL-14163, Clostridium bolteae, Clostrium bolteae 90A9, Dorea longicatena, Dorea longicatena CAG:42, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Blautia wexlerae, Turicibacter sanguinis, Lactobacillus mucosae and Bacteroides ovatus.

[0116] In some aspects, compositions of the disclosure include two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:121, and SEQ ID NO:122.

[0117] In one aspect, the disclosure provides composition A (see, e.g., FIG. 1, Table A). As shown in FIG. 1, composition A contains a strain comprising a 16S rDNA sequence of the nucleic acid sequence of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some embodiments, the disclosure provides a composition having two or more purified strains comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some embodiments, the disclosure provides a composition having five or more purified strains comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some aspects, the disclosure provides a composition having at least 10 purified strains, the strains comprising the 16S rDNA sequence of the nucleic acid sequence of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23, respectively. In some aspects, the disclosure provides a composition consisting of 10 purified strains, the strains comprising the 16S rDNA sequence of the nucleic acid sequence of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23, respectively. In some aspects, the disclosure provides a composition consisting essentially of 10 purified strains, the strains comprising the 16S rDNA sequence of the nucleic acid sequence of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23, respectively. As used herein, consisting essentially of refers to a composition that does not include additional strains.

[0118] In some aspects, the disclosure provides compositions having strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some aspects, the disclosure provides compositions having two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some aspects, the disclosure provides compositions having five or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some aspects, the disclosure provides a composition having at least 10 purified strains, the strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23, respectively. In some aspects, the disclosure provides a composition consisting of 10 purified strains, the strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23, respectively. In some aspects, the disclosure provides a composition consisting essentially of ten purified strains, the strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23, respectively.

[0119] The strains in composition A are related to the following bacterial species: Clostridium hathewayi, Blautia hansenii, Blautia producta, Blautia coccoides, Eubacterium contortum, Eubacterium fissicatena, Anaerostipes caccae, Clostridium scindens, Marvinbryanta formatexigens and Eisenbergiella tayi (see, e.g., Table 1). It should be understood that multiple strains of the compositions disclosed herein may have the same related bacterial species. For example, strains having 16S rDNA sequences of the nucleic acid sequences of SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 7 all have Blautia hansenii as a related species. In some aspects, the disclosure provides compositions having two or more bacteria of a species selected from the group consisting of Clostridium hathewayi, Blautia hansenii, Blautia producta, Blautia coccoides, Eubacterium contortum, Eubacterium fissicatena, Anaerostipes caccae, Clostridium scindens, Marvinbryanta formatexigens, and Eisenbergiella tayi. In some aspects, the disclosure provides compositions having two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:109, and SEQ ID NO:121.

[0120] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:13.

[0121] Each strain in composition A is BaiCD+, meaning that the strain expresses the bile-inducible operon gene BaiCD and / or the stereospecific NAD(H)-dependent 3-oxo-Δ 4 -means encoding or predicted to encode a protein having choline acid oxidoreductase activity. The BaiCD status of a strain can be determined, for example, by PCR (see, e.g., Wells et al. Clin Chim Acta (2003) May; 331(1-2): 127-34). Additionally, each strain of composition A is classified as belonging to Clostridium cluster XIVa. In some aspects, the disclosure provides a composition comprising two or more strains, wherein the strains are BaiCD+ strains. In some aspects, the disclosure provides a composition comprising two or more strains, wherein the strains are BaiCD+ and belong to Clostridium cluster XIVa. In some aspects of a composition comprising two or more strains that are BaiCD+ strains and belong to Clostridium cluster XIVa, the composition does not include a strain belonging to Clostridium cluster IV.

[0122] In some aspects, the disclosure provides a composition having two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:23, wherein all of the strains belong to Clostridium cluster XIVa.

[0123] [Table 1]

[0124] In one aspect, the disclosure provides composition B (see, e.g., FIG. 1, Table B). As shown in FIG. 1, composition B contains a strain comprising a 16S rDNA sequence of the nucleic acid sequence of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting ... and SEQ ID NO:21. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0125] In some embodiments, the composition comprises five or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition comprises five or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition comprises five or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the composition comprises five or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0126] In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NOs:124-159. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NOs:124-159. In some embodiments, the composition comprises at least eight purified strains comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0127] In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0128] In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NOs:124-159. In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NOs:124-159. In some embodiments, the composition consists essentially of at least eight purified strains comprising the 16S rDNA sequences of the nucleic acid sequences of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0129] In some embodiments, the composition includes eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition includes eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition includes eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the composition includes eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0130] In some embodiments, the composition comprises eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition comprises eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition comprises eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the composition comprises eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0131] In some embodiments, the composition consists essentially of eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition consists essentially of eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition consists essentially of eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the composition consists essentially of eight purified strains comprising the 16S rDNA sequences of the nucleic acid sequences of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0132] In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence of the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:124-159. In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence of the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence of the nucleic acid sequences of SEQ ID NO:124-159. In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence of the nucleic acid sequences of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0133] In some embodiments, the composition includes two or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition includes two or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition includes two or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition includes two or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152 and SEQ ID NO:157.

[0134] In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-145 and SEQ ID NOs:152-159. In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NOs:124-145 and SEQ ID NOs:152-159. In some embodiments, the composition includes five or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0135] In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition includes five or more purified strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0136] In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition comprises at least eight purified strains comprising the 16S rDNA sequences of the nucleic acid sequences of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0137] In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition consists essentially of at least eight purified strains comprising the 16S rDNA sequences of the nucleic acid sequences of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0138] In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In one aspect, the disclosure provides a composition containing a bacterial strain comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0139] In some embodiments, the composition includes two or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition includes two or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition includes two or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the compositions include two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152 and SEQ ID NO:157.

[0140] In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the compositions include five or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0141] In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the compositions include at least eight purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0142] In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition comprises at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the composition consists of at least eight purified strains comprising 16S rDNA sequences having at least 97% homology to the nucleic acid sequences of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0143] In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition consists essentially of at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159. In some embodiments, the composition consists essentially of at least eight purified strains comprising 16S rDNA sequences having at least 97% homology to the nucleic acid sequences of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157.

[0144] In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In one aspect, the disclosure provides a composition containing a strain comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159.

[0145] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-145 and SEQ ID NOs:152-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NOs:124-145 and SEQ ID NOs:152-159.

[0146] In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:20, SEQ ID NO:124-145, and SEQ ID NO:152-159.

[0147] In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition includes at least eight purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159.

[0148] In some embodiments, the composition comprises at least eight purified strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159, respectively. In some embodiments, the composition comprises at least eight purified strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22, respectively. In some embodiments, the composition comprises at least eight purified strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159, respectively.

[0149] In some embodiments, the composition consists essentially of at least eight purified strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159, respectively. In some embodiments, the composition consists essentially of at least eight purified strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22, respectively. In some embodiments, the composition consists essentially of at least eight purified strains comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:22, SEQ ID NO:124-145, and SEQ ID NO:152-159, respectively.

[0150] In one aspect, the disclosure provides a composition comprising a strain comprising a 16S rDNA sequence of the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:124-159. In one aspect, the disclosure provides a composition comprising a strain comprising a 16S rDNA sequence of the nucleic acid sequences of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22. In one aspect, the disclosure provides a composition comprising a strain comprising a 16S rDNA sequence of the nucleic acid sequences of SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NO:124-159.

[0151] In some embodiments, the composition includes two or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-159. In some embodiments, the composition includes two or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition includes two or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NOs:124-159.

[0152] In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-159. In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition includes five or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NOs:124-159.

[0153] In some embodiments, the composition includes at least 10 purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-159. In some embodiments, the composition includes at least 10 purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition includes at least 10 purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NOs:124-159.

[0154] In some embodiments, the composition comprises ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:124-159. In some embodiments, the composition comprises ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition comprises ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NO:124-159.

[0155] In some embodiments, the composition consists essentially of ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-159. In some embodiments, the composition consists essentially of ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition consists essentially of ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NOs:124-159.

[0156] The strains in composition B relate to the following bacterial species: Flavinofractor plautii, Lachnospiraceae, bacterium 7_1_58FAA, Subdoligranulum Anaerotruncus colihominis, Eubacterium fissicatena, Ruminococcus torques Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta, Clostridium innocuum and Erysipelotrichaceae_bacterium_21-3 (see, for example, Table 2).

[0157] The selected strains were subjected to whole genome sequencing using the PacBio Biosciences platform (Menlo Park, CA) and the sequences were assembled into whole genomes (Table 3). 16S rDNA sequences were identified using Prokka and Barrnap. Some strains were found to contain more than one 16S sequence. Then, using the usearch (v5.2.236) algorithm, all identified 16S rRNA gene nucleotide sequences per strain were clustered at 97 percent identity, and the cluster seed sequence was selected as the representative sequence per strain in composition B (consensus 16S sequence: column labeled "*Consensus sequence number of 16S region determined by WGS" in Table 3). Table 3 provides the identification results of the strains included in the indicated composition B based on Sanger sequencing of the 16S region and whole genome sequencing (WGS). The closest species of the strains was identified by comparison with both the 16S database (column labeled "Closest species based on consensus sequence of 16S region compared to 16S database") and the whole genome database (column labeled "Closest species based on WGS compared to WG database").

[0158] The strains in Composition B are related to the following bacterial species based on identification of 16S sequences by whole genome sequencing and comparison of these sequences with 16S databases: Clostridium bolteae, Anaerotruncus colihominis, Dracourtella massiliensis, Clostridium symbiosum Blautia producta, Dorea longicatena Clostridium innocuum and Flavinofractor plautii (see, e.g., Table 3).

[0159] Based on whole genome sequencing and comparison of the whole genome against whole genome databases, the strains of Composition B are most closely related to the following bacterial species: Clostridium bolteae 90A9, Anaerotruncus colihominis DSM 17241, Dracourtella massiliensis GD1, Clostridium symbiosum WAL-14163, Clostridium bacterium UC5.1-1D4, Dorea longicatena CAG:42, Erysipelotrichaceae bacterium 21_3 and Clostridium orbiscindens 1_3_50AFAA (see, e.g., Table 3).

[0160] It should be understood that the strains of the compositions disclosed herein may have the same related bacterial species. For example, the strains comprising the 16S rDNA sequences having the nucleic acid sequences of SEQ ID NO:18, SEQ ID NO:20 and SEQ ID NO:22 all have Dorea longicatena as related bacterial species. In some aspects, the disclosure provides compositions comprising two or more bacteria selected from the group consisting of Flavinofractor plautii, Lachnospiraceae, bacterium 7_1_58FAA, Subdoligranulum Anaerotruncus colihominis, Eubacterium fissicatena, Ruminococcus torques Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta, Clostridium innocuum and Erysipelotrichaceae_bacterium_21-3. In some embodiments, the disclosure provides compositions having two or more bacteria selected from the group consisting of Flavinofractor plautii, Anaerotruncus colihominis, Eubacterium fissicatena, Clostridium symbiosum, Clostridium bolteae, Dorea longicatena, Blautia producta, and Clostridium innocuum. In some embodiments, the disclosure provides compositions including two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, and SEQ ID NO:122.

[0161] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:124-159. In some embodiments, the compositions comprise two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152 and SEQ ID NO:157.

[0162] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:124-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NO:124-159. In some embodiments, the compositions comprise two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152 and SEQ ID NO:157.

[0163] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, and SEQ ID NO:124-159. In some embodiments, the compositions comprise two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152 and SEQ ID NO:157.

[0164] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-145 and SEQ ID NOs:151-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NOs:124-145 and SEQ ID NOs:151-159. In some embodiments, the compositions comprise two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:152 and SEQ ID NO:157.

[0165] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:124-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159.

[0166] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:124-145, and SEQ ID NO:152-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, 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:21. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:124-145, and SEQ ID NO:152-159.

[0167] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:157-159, and SEQ ID NO:141-156. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, SEQ ID NO:157-159, and SEQ ID NO:141-156.

[0168] Each bacterium in composition B is a BaiCD-strain, which means that the strain expresses the bile-inducible operon gene baiCD and / or the stereospecific NAD(H)-dependent 3-oxo-Δ 4-meaning that it does not encode and / or is not predicted to encode a protein having choline acid oxidoreductase activity. In some embodiments, the disclosure provides a composition comprising two or more bacteria, the bacteria being BaiCD-strains. The strains of composition B are classified as belonging to Clostridium clusters IV, XIVa and XVII. In some embodiments, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium clusters IV, XIVa or XVII. In some embodiments, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium clusters IV or XVII. In some embodiments, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium clusters XIVa or XVII. In some embodiments, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium clusters IV or XIVa. In some embodiments, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium clusters IV or XIVa. In some aspects, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium cluster IV. In some aspects, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium cluster XIVa. In some aspects, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium cluster XVII. In some aspects, the disclosure provides two or more strains, the bacteria being BaiCD-strains and belonging to Clostridium cluster IV, XIVa, and XVII, but not belonging to Clostridium cluster XVI or XVIII.

[0169] In some aspects, the disclosure provides two or more strains, wherein the strains are spore-forming strains. In some aspects, the disclosure provides two or more strains, wherein the bacteria are spore-forming bacteria and the strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:21, SEQ ID NOs:124-140, and SEQ ID NOs:152-156. In some aspects, the disclosure provides two or more strains, wherein the bacteria are spore-forming bacteria and the strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:17, and SEQ ID NO:21. In some aspects, the disclosure provides two or more strains, wherein the bacteria are spore-forming bacteria and the strains comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 124-140 and 152-156.

[0170] In some embodiments, the disclosure provides two or more strains, where the bacteria include both sporulating and non-sporulating bacteria. In some embodiments, the disclosure provides two or more strains, where the bacteria include both sporulating and non-sporulating bacteria, and the sporulating strains include two or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:21, SEQ ID NO:124-140, and SEQ ID NO:152-156. In some embodiments, the disclosure provides two or more strains, where the bacteria include both sporulating and non-sporulating bacteria, and the sporulating strains include two or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:17, and SEQ ID NO:21. In some aspects, the disclosure provides two or more strains, where the bacteria encompass both spore-forming and non-spore-forming bacteria, and the spore-forming strains include two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 124-140 and SEQ ID NOs: 152-156.

[0171] [Table 2]

[0172] In some embodiments, the composition comprises one or more bacterial species from the genus Bacteroides. In some embodiments, the composition comprises one or more bacterial species selected from the group consisting of B. acidifaciens, B. caccae, B. coprocola, B. coprosuis, B. eggerthii, B. finegoldii, B. fragilis, B. helcogenes, B. intestinalis, B. massiliensis, B. nordii, B. ovatus, B. thetaiotaomicron, B. vulgatus, B. plebeius, B. uniformis, B. salyersai, B. pyogenes, B. goldsteinii, B. dorei, and B. johnsonii. In some embodiments, the composition comprises Bacteroides ovatus. In some embodiments, the Bacteroides ovatus has a 16S rDNA sequence comprising SEQ ID NO:83. In some embodiments, the Bacteroides ovatus has a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence comprising SEQ ID NO: 83. In some embodiments, the Bacteroides ovatus has a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence comprising SEQ ID NO: 101.

[0173] Without being limited to a particular mechanism, it is believed that the inclusion of Bacteroides species in the bacterial compositions disclosed herein increases the ability of the bacteria to sense and adapt to nutrient availability or affect the host immune system so that it is more effective in fighting pathogens (such as C. difficile). In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:124-159, and SEQ ID NO:83. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:83. (See Composition B1, e.g., Table B1). In some embodiments, the compositions comprise two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:124-159 and SEQ ID NO:83.

[0174] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-145, SEQ ID NO:152-159, and SEQ ID NO:83. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:83. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-145, SEQ ID NO:152-159, and SEQ ID NO:83.

[0175] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:124-159, and SEQ ID NO:83. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:83. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:124-159, SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NO:83.

[0176] In some embodiments, the compositions comprise two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO: 93, SEQ ID NO: 95, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 106, SEQ ID NO: 110, and SEQ ID NO: 122. It should be understood that the compositions disclosed herein, in some embodiments, do not encompass bacterial species from the genus Bacteroides.

[0177] [Table 3]

[0178] In some aspects, the compositions disclosed herein do not include Clostridium orbiscindens 1_3_50AFAA, Flavinofractor plautii, Subdoligranulum, or Lachnospiraceae bacterium 7_1_58FAA. In some aspects, the compositions disclosed herein do not include Clostridium orbiscindens 1_3_50AFAA. In some aspects, the compositions disclosed herein do not include Flavinofractor plautii. In some aspects, the compositions disclosed herein do not include Subdoligranulum. In some aspects, the compositions disclosed herein do not include Lachnospiraceae bacterium 7_1_58FAA.

[0179] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NOs:124-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10 and SEQ ID NOs:157-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 124-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NOs: 157-159.

[0180] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-146 and SEQ ID NOs:152-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10 and SEQ ID NOs:157-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:22, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NOs:124-146, and SEQ ID NOs:152-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NOs:157-159.

[0181] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NOs:124-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10 and SEQ ID NOs:157-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:22, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:22, and SEQ ID NOs:124-159, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NOs:157-159.

[0182] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, and SEQ ID NO:122, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:93.

[0183] In some embodiments, the composition includes one or more bacterial species from the genus Bacteroides, and does not include Clostridium orbiscindens 1_3_50AFAA, Flavinofractor plautii, Subdoligranulum, or Lachnospiraceae bacterium 7_1_58FAA. (See composition B2, e.g., Table B2.) In some embodiments, the composition includes Bacteroides ovatus, and does not include Clostridium orbiscindens 1_3_50AFAA, Flavinofractor plautii, Subdoligranulum, or Lachnospiraceae bacterium 7_1_58FAA.

[0184] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:83, and SEQ ID NOs:124-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10 and SEQ ID NOs:157-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:83, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:83 and SEQ ID NOs:124-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NOs:157-159.

[0185] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:83, SEQ ID NO:124-145, and SEQ ID NO:152-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10 and SEQ ID NO:157-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:83, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:83, SEQ ID NOs:124-145, and SEQ ID NOs:152-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NOs:157-159.

[0186] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:83, and SEQ ID NO:124-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10 and SEQ ID NO:157-159. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:83, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NO:10. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:83, and SEQ ID NOs:124-156, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence of SEQ ID NOs:157-159.

[0187] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, and SEQ ID NO:122, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:93.

[0188] [Table 4]

[0189] In one aspect, the disclosure provides composition C (see, e.g., FIG. 1, Table C). As shown in FIG. 1, composition C contains bacteria having the following 16S rDNA sequences: SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the disclosure provides a composition having two or more purified strains comprising a 16S rDNA sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the composition encompasses four or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the composition includes at least 10 purified strains comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the composition consists of 10 purified strains comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16, respectively. In some embodiments, the composition consists essentially of 10 purified strains comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16, respectively.

[0190] In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the composition comprises four or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the composition comprises at least ten purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the composition consists of ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the composition consists essentially of ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16.

[0191] The bacterial strains in composition C relate to the following species: Clostridium scindens, Clostridium hathewayi, Blautia hansenii, Blautia wexlerae, Blautia producta, Blautia coccoides, Dorea longicatena, Clostridium innocuum, Flavinofractor plautii, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Anaerotruncus colihominis and Clostridium symbiosum. In some aspects, the disclosure provides compositions having two or more strains of a species selected from the group consisting of Clostridium scindens, Clostridium hathewayi, Blautia hansenii, Blautia wexlerae, Blautia producta, Blautia coccoides, Dorea longicatena, Clostridium innocuum, Flavinofractor plautii, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Anaerotruncus colihominis, and Clostridium symbiosum. In some aspects, the disclosure provides compositions comprising two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:106, and SEQ ID NO:122.

[0192] In some embodiments, the compositions disclosed herein do not include Flavinofractor plautii, Subdoligranulum, or Lachnospiraceae bacterium 7_1_58FAA. In some embodiments, the compositions include two or more purified strains that include a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:7, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:14, and SEQ ID NO:16, and the compositions do not include a strain that includes a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:10. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:106, and SEQ ID NO:122, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:93.

[0193] The strains of composition C include both BaiCD+ and BaiCD- strains. In some embodiments, the disclosure provides a composition comprising two or more bacteria, where one or more bacteria are BaiCD+ strains and one or more bacteria are BaiCD- strains. In some embodiments, the one or more bacteria that are BaiCD+ strains are selected from strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, and SEQ ID NO:7. In some embodiments, the one or more bacteria that are BaiCD- strains are selected from strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:14, and SEQ ID NO:16. In some embodiments, the one or more bacteria that are BaiCD+ strains are selected from the bacterial species Clostridium scindens, Clostridium hathewayi, Blautia hansenii, Blautia wexlerae, Blautia product, and Blautia coccoides. In some embodiments, the one or more bacteria that are BaiCD- strains are selected from the bacterial species Dorea longicatena, Clostridium innocuum, Flavonifractor plautii, or Lachnospiraceae bacterium 7_1_58FAA, Anaerotruncus colihominis, and Clostridium symbiosum. The Clostridium genus strains of composition C are classified as belonging to Clostridium clusters IV, XIVa, and XVII. In some aspects, the disclosure provides two or more strains, the bacteria being BaiCD- and BaiCD+ strains, belonging to Clostridium cluster IV, XIVa, or XVII. In some aspects, the disclosure provides two or more strains, the bacteria being BaiCD- and BaiCD+ strains, belonging to Clostridium cluster XIVa or XVII. In some aspects, the disclosure provides two or more strains, the bacteria being BaiCD- and BaiCD+ strains, belonging to Clostridium cluster IV or XIVa.

[0194]

Table 5

[0195] In one aspect, the disclosure provides composition D (see, e.g., FIG. 1, Table D). As shown in FIG. 1, composition D contains bacteria having the following 16S rDNA sequences: SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6. In some embodiments, the disclosure provides a composition having two or more purified strains comprising a 16S rDNA sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6. In some embodiments, the disclosure provides a composition including three or more purified strains comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6. In some aspects, the disclosure provides a composition comprising at least 10 purified strains comprising a 16S rDNA sequence of a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6. In some aspects, the disclosure provides a composition consisting of 10 purified strains comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6, respectively. In some aspects, the disclosure provides a composition consisting essentially of 10 purified strains comprising a 16S rDNA sequence of a nucleic acid sequence of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6, respectively. In some aspects, the disclosure provides a composition comprising two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6.In some aspects, the disclosure provides a composition that includes three or more purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6. In some aspects, the disclosure provides a composition that includes at least ten purified strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6. In some aspects, the disclosure provides a composition that consists of ten purified strains that each include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6. In some aspects, the disclosure provides a composition consisting essentially of ten purified strains each comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequences of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, SEQ ID NO:2, and SEQ ID NO:6.

[0196] The bacterial strains in composition D are related to the following bacteria: Clostridium scindens, Clostridium hathewayi, Blautia hansenii, Blautia wexlerae, Anaerotruncus colihominis, Dorea longicatena, Clostridium innocuum, Flavinofractor plautii, Lachnospiraceae bacterium 7_1_58FAA, Subdoligranulum, Turicibacter sanguinis and Lactobacillus mucosae. In some aspects, the disclosure provides compositions having two or more strains selected from the group of species consisting of Clostridium scindens, Clostridium hathewayi, Blautia hansenii, Blautia wexlerae, Anaerotruncus colihominis, Dorea longicatena, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Flavinofractor plautii, Lachnospiraceae bacterium 7_1_58FAA, Turicibacter sanguinis, and Lactobacillus mucosae. In some aspects, the disclosure provides compositions having two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, and SEQ ID NO:105.

[0197] In some embodiments, the compositions disclosed herein do not include Flavinofractor plautii, Subdoligranulum, or Lachnospiraceae bacterium 7_1_58FAA. In some embodiments, the compositions include two or more purified strains that include a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:2, and SEQ ID NO:6, and the compositions do not include a strain that includes a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:10. In some embodiments, the composition comprises two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99 and SEQ ID NO:105, and the composition does not include a strain comprising a 16S rDNA sequence having at least 97% homology to the nucleic acid sequence of SEQ ID NO:93.

[0198] The strains of composition D include both BaiCD+ and BaiCD- strains. In some embodiments, the disclosure provides a composition comprising two or more bacteria, where one or more bacteria are BaiCD+ strains and one or more bacteria are BaiCD- strains. In some embodiments, the one or more bacteria that are BaiCD+ strains are selected from strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:5, and SEQ ID NO:1. In some embodiments, the one or more bacteria that are BaiCD- strains are selected from strains that include a 16S rDNA sequence that has at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:10, and SEQ ID NO:14. In some embodiments, the one or more bacteria that are BaiCD+ strains are selected from the bacterial species Clostridium scindens, Clostridium hathewayi, Blautia hansenii, and Blautia wexlerae. In some embodiments, the one or more bacteria that are BaiCD- strains are selected from the bacterial species Dorea longicatena, Clostridium innocuum, Flavonifractor plautii, and Anaerotruncus colihominis. The Clostridium genus strains of composition D are classified as belonging to Clostridium clusters IV, XIVa, and XVII. In some embodiments, the disclosure provides two or more strains, the bacteria are BaiCD- strains and BaiCD+ strains, and belong to Clostridium clusters IV, XIVa, or XVII. In some embodiments, the disclosure provides two or more strains, the bacteria are BaiCD- strains and BaiCD+ strains, and belong to Clostridium clusters XIVa or XVII. In some embodiments, the disclosure provides two or more strains, the bacteria are BaiCD- strains and BaiCD+ strains, and belong to Clostridium clusters IV or XIVa.

[0199] Compound D is Clostridium-free Turicibact sanguinis and Lactobacillus mucosae and the smooth mucous membrane is 2 and one of the skeletal muscles The ingredient contains the active ingredient Clostridium The main ingredient in the preparation is specific Clostridium ingredient Lactobac illus strain and Lactobacillus strain L. acetotolerance、L. acidifarinae、L. acidipiscis、L. acidophilus、L. agilis、L. algidus、L. alimentarius、L. amylolyticus、L. amylophilus、L. amylotrophicus、L. amylovorus、L. animalis、L. antri、L. apodemi、L. aviarius、L. bifermentans、L. brevis、L. buchneri、L. camelliae、L. casei、L. catenaformis、L. ceti、L. coleohominis、L. collinoides、L. compost、L. concavus、L. coryniformis、L. crispatus、L. crustorum、L. curvatus、L. delbrueckii subsp. bulgaricus、L. delbrueckii subsp. delbrueckii、L. delbrueckii subsp. lactis、L. dextrinicus、L. diolivorans、L. equi、L. equigenerosi、L. farraginis、L. farciminis、L. fermentum、L. fornicalis、L. fructivorans、L. frumenti、L. fuchuensis、L. gallinarum、L. gasseri、L. gastricus、L. ghanensis、L. graminis、L. hammesii、L. hamstery、L. harbinensis、L. hayakitensis、L. helveticus、L.hilgardii, L. homohiochii, L. iners, L. ingluviei, L. intestinalis, L. jensenii, L. johnsonii, L. kalixensis, L.kefiranofaciens, L. kefiri, L. kimchii, L. kitasatonis, L. kunkeei, L. leichmannii, L. lindneri, L. malefermentans, L. mali, L. manihotivorans, L. mindensis, L. mucosae, L. murinus, L. nagelii, L. namurensis, L. nantensis, L. oligofermentans, L. oris, L. panis, L. pantheris, L. parabrevis, L. parabuchneri, L. paracasei, L. paracollinoides, L. parafarraginis, L. parakefiri, L. paraalimentarius, L. paraplantarum, L. pentosus, L. perolens, L. plantarum, L. pontis, L. protectus, L. psittaci, L. rennini, L. reuteri, L. rhamnosus, L. rimae, L. rogosae, L. rossiae, L. ruminis, L. saerimneri, L. sakei, L. salivarius, L. sanfranciscensis, L. satsumensis, L. secaliphilus, L. sharpeae, L. siliginis, L. spicheri, L. suebicus, L. thailandensis, L. ultunensis, L. vaccinostercus, L. vaginalis, L. versmoldensis, L. vini, L. vitulinus, L. zeae and L.zymae. In some embodiments, the non-Clostridium strain is Lactobacillus mucosae. In some embodiments, the non-Clostridium strain is Lactobacillus mucosae. In some embodiments, the Lactobacillus mucosae has a 16S rDNA sequence comprising SEQ ID NO:2. In some embodiments, the Lactobacillus mucosae has a 16S rDNA sequence having at least 97% homology to a nucleic acid comprising SEQ ID NO:2. In some embodiments, the Lactobacillus mucosae has a 16S rDNA sequence having at least 97% homology to a nucleic acid comprising SEQ ID NO:91.

[0200] In some aspects, the disclosure provides compositions comprising two or more bacteria, the compositions encompassing both Clostridium and non-Clostridium strains. In some aspects, the non-Clostridium strain is a member of the Turicibacter genus. In some aspects, the non-Clostridium strain is Turicibacter sanguinis. In some aspects, the Turicibacter sanguinis has a 16S rDNA sequence comprising SEQ ID NO:6. In some aspects, the Turicibacter sanguinis has a 16S rDNA sequence having at least 97% homology to a nucleic acid comprising SEQ ID NO:6. In some aspects, the Turicibacter sanguinis has a 16S rDNA sequence having at least 97% homology to a nucleic acid comprising SEQ ID NO:90.

[0201] In some aspects, the disclosure provides compositions comprising two or more bacteria, the compositions including both Clostridium and non-Clostridium strains, hi some aspects, the non-Clostridium strains are Lactobacillus mucosae and Turicibacter sanguinis.

[0202] In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Lactobacillus. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Turicibacter. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Lactobacillus or Turicibacter. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition includes only Clostridium strains. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition includes only Clostridium strains belonging to Clostridium cluster IV, XIVa or XVII strains. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Clostridium cluster XI strains.

[0203] In some aspects, the disclosure provides compositions comprising two or more purified strains selected from the group consisting of Clostridium scindens, Pseudoflavonifractor capillosus, and Blautia hansenii. In some aspects, the compositions disclosed herein do not include Clostridium scindens, Pseudoflavonifractor capillosus, or Blautia hansenii.

[0204] [Table 6]

[0205] In one aspect, the disclosure provides composition F (see, eg, Figures 13 and 14, and Tables F1 and F2). As shown in FIG. 13, Composition F contains bacteria having the following 16S rDNA sequences: SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, 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, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, and SEQ ID NO:79.

[0206] In some aspects, the disclosure provides a 16S sequence selected from the group consisting of SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, 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, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, and SEQ ID NO:79. A composition is provided having two or more purified strains that contain rDNA sequences.

[0207] In some embodiments, the composition comprises SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, 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, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO: 53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78 and SEQ ID NO:79.

[0208] The strains in composition F are related to the following bacteria: Dorea longicatena, Ruminococcus obeum, Megasphaera elsdenii, Acidaminococcus fermentans, Acidaminococcus intestine, Megasphaera elsdenii, Ruminococcus faecis, Bacteroides cellulosilyticus, Anaerostipes hadrus, Ruminococcus obeum, Flavonifractor plautii, Eubacterium rectale, Flavonifractor plautii, Megasphaera elsdenii, Eubacterium rectale, Ruminococcus champanellensis, Ruminococcus albus, Ruminococcus champanellensis, Ruminococcus faecis, Bifidobacterium bifidum, Anaerostipes hadrus, Anaerostipes hadrus, Anaerostipes hadrus, Eubacterium rectale, Ruminococcus faecis, Blautia luti, Ruminococcus faecis, Anaerostipes hadrus, Anaerostipes hadrus, Ruminococcus faecis, Eubacterium rectale, Eubacterium rectale, Anaerostipes hadrus, Ruminococcus faecis, Ruminococcus faecis, Dorea longicatena, Roseburia faecis, Blautia luti, Fusicatenibacter saccharivorans, Fusicatenibacter saccharivorans, Roseburia faecis, Megasphaera elsdenii, Eubacterium rectale, Eubacterium rectale, Roseburia faecis, Blautia faecis, Fusicatenibactersaccharivorans and Dorea formicigenerans.

[0209] In some embodiments, the present disclosure provides a method for the preparation of a microorganism comprising: Dorea longicatena, Ruminococcus obeum, Megasphaera elsdenii, Acidaminococcus fermentans, Acidaminococcus intestine, Megasphaera elsdenii, Ruminococcus faecis, Bacteroides cellulosilyticus, Anaerostipes hadrus, Ruminococcus obeum, Flavonifractor plautii, Eubacterium rectale, Flavonifractor plautii, Megasphaera elsdenii, Eubacterium rectale, Ruminococcus champanellensis, Ruminococcus albus, Ruminococcus champanellensis, Ruminococcus faecis, Bifidobacterium bifidum, Anaerostipes hadrus, Anaerostipes hadrus, Anaerostipes hadrus, Eubacterium rectale, Ruminococcus faecis, Blautia luti, Ruminococcus faecis, Anaerostipes hadrus, Anaerostipes hadrus, Ruminococcus faecis, Eubacterium rectale, Eubacterium rectale, Anaerostipes hadrus, Ruminococcus faecis, Ruminococcus faecis, Dorea longicatena, Roseburia faecis, Blautia luti, Fusicatenibacter saccharivorans, Fusicatenibacter saccharivorans, Roseburia faecis, Megasphaera elsdenii, Eubacterium rectale, Eubacterium rectale, Roseburia faecis, Blautia faecis, FusicatenibacterThe present invention provides a composition having two or more strains of a species selected from the group consisting of Dorea saccharivorans and Dorea formicigenerans.

[0210] In some aspects, the disclosure provides compositions comprising two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119 and SEQ ID NO:120. It should be understood that the multiple strains of the compositions disclosed herein may have the same related bacterial species. For example, composition F comprises 12 strains having Eubacterium rectale as the closest relative.

[0211] In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IV. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XIVa. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IX. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IV. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XIVa and at least one of the strains belongs to Clostridium cluster IX. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IV, at least one of the strains of the composition belongs to Clostridium cluster XIVa and at least one of the strains of the composition belongs to Clostridium cluster IX. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IV, at least one of the strains of the composition belongs to Clostridium cluster XIVa and at least one of the strains of the composition belongs to Clostridium cluster IX. In some aspects, the compositions provided herein do not include strains belonging to Clostridium cluster XVIII. In some aspects, the compositions provided herein do not include strains belonging to Clostridium cluster XVI or XVIII.

[0212] Composition F includes a non-Clostridium strain. In some embodiments, the disclosure provides compositions comprising two or more bacteria, the compositions including both Clostridium and non-Clostridium strains. In some embodiments, the non-Clostridium strain is a member of the Bacteroides genus. In some embodiments, the non-Clostridium strain is Bacteroides cellulosilyticus. In some embodiments, the non-Clostridium strain is a member of the Bifidobacterium genus. In some embodiments, the non-Clostridium strain is Bifidobacterium bifidum. In some embodiments, the disclosure provides compositions comprising two or more strains, the compositions including both Clostridium and non-Clostridium strains, the non-Clostridium strains are Bacteroides cellulosilyticus and Bifidobacterium bifidum.

[0213] In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Bacteroides. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Bifidobacterium. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Bacteroides and does not include Bifidobacterium. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include a non-Clostridium strain. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition includes only Clostridium strains belonging to Clostridium cluster IV, XIVa or XVII strains. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Clostridium cluster XI strains.

[0214] Table F1 Composition F [Table 7]

[0215] Table F2 Composition F, grouping of strains [Table 8] *Legend for short chain fatty acids: A, acetate; B, butyrate; L, lactate; P, propionate; S, succinate

[0216] In one aspect, the disclosure provides composition G (see, eg, FIG. 19, Table G). As shown in FIG. 19, composition G contains bacteria having the following 16S rDNA sequence: SEQ ID NO:27, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:68, SEQ ID NO:72, SEQ ID NO:70, SEQ ID NO:24, SEQ ID NO:34, SEQ ID NO:37, SEQ ID NO:46, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:35, SEQ ID NO:62, SEQ ID NO:26, SEQ ID NO:63, SEQ ID NO:67, SEQ ID NO:40, SEQ ID NO:38, SEQ ID NO:47, SEQ ID NO:56, SEQ ID NO:25 and SEQ ID NO:32.

[0217] In some aspects, the disclosure provides a composition having two or more purified strains comprising a 16S rDNA sequence selected from the group consisting of SEQ ID NO:27, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:68, SEQ ID NO:72, SEQ ID NO:70, SEQ ID NO:24, SEQ ID NO:34, SEQ ID NO:37, SEQ ID NO:46, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:35, SEQ ID NO:62, SEQ ID NO:26, SEQ ID NO:63, SEQ ID NO:67, SEQ ID NO:40, SEQ ID NO:38, SEQ ID NO:47, SEQ ID NO:56, SEQ ID NO:25, and SEQ ID NO:32.

[0218] In some embodiments, the compositions include two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:27, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:68, SEQ ID NO:72, SEQ ID NO:70, SEQ ID NO:24, SEQ ID NO:34, SEQ ID NO:37, SEQ ID NO:46, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:35, SEQ ID NO:62, SEQ ID NO:26, SEQ ID NO:63, SEQ ID NO:67, SEQ ID NO:40, SEQ ID NO:38, SEQ ID NO:47, SEQ ID NO:56, SEQ ID NO:25, and SEQ ID NO:32.

[0219] The strains in composition G are related to the following bacteria: Acidaminococcus fermentans, Acidaminococcus intestine, Anaerostipes hadrus, Blautia faecis, Blautia hansenii, Dorea formicigenerans, Dorea longicatena, Eubacterium rectale, Flavinofractor plautii, Fusicatenibacter saccharivorans, Megasphaera elsdenii, Roseburia faecis, Ruminococcus champanellensis, Ruminococcus albus, Ruminococcus faecis and Ruminococcus obeum.

[0220] In some aspects, the disclosure provides compositions having two or more strains of a species selected from the group consisting of Acidaminococcus fermentans, Acidaminococcus intestine, Anaerostipes hadrus, Blautia faecis, Blautia hansenii, Dorea formicigenerans, Dorea longicatena, Eubacterium rectale, Flavinofractor plautii, Fusicatenibacter saccharivorans, Megasphaera elsdenii, Roseburia faecis, Ruminococcus champanellensis, Ruminococcus albus, Ruminococcus faecis, and Ruminococcus obeum.

[0221] In some aspects, the disclosure provides a composition including two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:104, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, and SEQ ID NO:119.

[0222] Table G Composition G [Table 9]

[0223] In one aspect, the disclosure provides composition H (see, e.g., FIG. 26, Table H). As shown in FIG. 26, composition H contains bacteria having the following 16S rDNA sequences: SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:21, SEQ ID NO:82, SEQ ID NO:81, and SEQ ID NO:80. In some embodiments, the disclosure provides compositions having two or more purified strains comprising a 16S rDNA sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:21, SEQ ID NO:82, SEQ ID NO:81, and SEQ ID NO:80.

[0224] In some embodiments, the composition includes two or more purified strains that comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:21, SEQ ID NO:82, SEQ ID NO:81, and SEQ ID NO:80. In some embodiments, the composition includes four or more purified strains that comprise a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:21, SEQ ID NO:82, SEQ ID NO:81, and SEQ ID NO:80.

[0225] The strains in composition H are associated with the following bacteria: Anaerotruncus colihominis, Clostridium symbiosum, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Clostridium disporicum, Clostridium bolteae, and Erysipelatoclostridium ramosum. In some aspects, the disclosure provides compositions having two or more strains selected from the group consisting of Anaerotruncus colihominis, Clostridium symbiosum, Clostridium innocuum, Erysipelotrichaceae_bacterium_21-3, Clostridium disporicum, Clostridium bolteae, and Erysipelatoclostridium ramosum. In some aspects, the disclosure provides a composition comprising two or more purified strains comprising a 16S rDNA sequence having at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NO:86, SEQ ID NO:95, SEQ ID NO:98, SEQ ID NO:110, SEQ ID NO:122, and SEQ ID NO:123.

[0226] Composition H includes bacteria from Clostridium clusters I, IV, XIVa, XVII, and XVIII. In some embodiments, the disclosure provides compositions including two or more purified strains from Clostridium clusters I, IV, XIVa, XVII, and XVIII. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster IV. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XIVa. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XVII. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster I. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XVIII. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XIVa and at least one of the strains belongs to Clostridium cluster IV. In some embodiments, at least one of the strains of the composition belongs to Clostridium cluster XIVa and at least one of the strains belongs to Clostridium cluster XVII.

[0227] Table H [Table 10]

[0228] In some aspects, the disclosure provides compositions comprising two or more bacteria, where the composition does not include a bacterium from Clostridium cluster I. In some aspects, the disclosure provides compositions comprising two or more bacteria, where the composition does not include a bacterium from Clostridium cluster XVIII. In some aspects, the disclosure provides compositions comprising two or more bacteria, where the composition does not include a bacterium from Clostridium cluster I and does not include a bacterium from Clostridium cluster XVIII.

[0229] In some aspects, the disclosure provides a composition comprising two or more bacteria, where all of the bacteria are anaerobic. In some aspects, the disclosure provides a composition comprising two or more bacteria, where all of the bacteria are obligate anaerobic.

[0230] In some aspects, the disclosure provides a composition comprising two or more bacteria (e.g., purified strains), where the composition does not include Clostridium scindens. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Flavonifractor plautii. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Parabacteroides. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Lactobacillus. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Colinsella. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Dialister. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Raoultella. In some aspects, the disclosure provides a composition comprising two or more bacteria, where the composition does not include Streptococcus. In some aspects, the disclosure provides a composition comprising two or more bacteria, wherein the composition does not include Staphylococcus. In some aspects, the disclosure provides a composition comprising two or more bacteria, wherein the composition does not include Microbacterium. In some aspects, the disclosure provides a composition comprising two or more bacteria, wherein the composition does not include Proteobacteria. In some aspects, the disclosure provides a composition comprising two or more bacteria, wherein the composition does not include Peptostreptococcaceae. In some aspects, the disclosure provides a composition comprising two or more bacteria, wherein the composition does not include Oscillospiraceae.

[0231] In one aspect, the disclosure provides a strain having a 16S rDNA sequence that has a homology to any one of the nucleic acid sequences of the strains or species sequences described herein. In some embodiments, the strain has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8% or 99.9% homology to any of the strains or bacterial species described herein over the specified region or over the entire sequence. Those skilled in the art will recognize that the term "homology" or "percent homology" in the context of two or more nucleic acid or amino acid sequences refers to a measure of similarity between two or more sequences or a portion or portions thereof. Homology can exist over a region in the sequence that is at least about 50 nucleotides in length, or more preferably over a region that is 100-500 or 1000 or more nucleotides in length. In some embodiments, homology exists over the length of the 16S rRNA or 16S rDNA sequence, or a portion thereof.

[0232] Additionally or alternatively, two or more sequences may be calculated for identity between the sequences. The term "identical" or percent "identity" in the context of two or more nucleic acid or amino acid sequences refers to two or more sequences or subsequences that are the same. Two sequences are "substantially identical" if they have a specified percentage of the same (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8% or 99.9% identical) amino acid residues or nucleotides over a specified region or throughout the entire sequence when compared and aligned for maximum correspondence over a comparison window or specified region, as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the identity exists over a region at least about 50 nucleotides in length, or more preferably over a region 100-500 or 1000 or more nucleotides in length. In some embodiments, the identity exists over the length of the 16S rRNA or 16S rDNA sequence.

[0233] Additionally or alternatively, two or more sequences may be calculated for alignment between sequences. The term "alignment" or "percent alignment" in the context of two or more nucleic acid or amino acid sequences refers to two or more sequences or subsequences that are the same. Two sequences are "substantially aligned" if they have a specified percentage of the same (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8% or 99.9% identical) amino acid residues or nucleotides over a specified region or over the entire sequence when compared and aligned for maximum identity over a comparison window or specified region, as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the alignment exists over a region at least about 50 nucleotides long, or preferably over a region 100 to 500 or 1000 or more nucleotides long. In some embodiments, identity exists across the entire 16S rRNA or 16S rDNA sequence.

[0234] In sequence comparison, typically one sequence serves as a reference sequence to which test sequences are compared. Methods of sequence alignment for comparison are well known in the art. See, e.g., by the local homology algorithm of Smith and Waterman (1970) Adv. Appl. Math. 2:482c, by the homology alignment algorithm of Needleman and Wunsch, J. Mol. Biol. (1970) 48:443, by the similarity searching methods of Pearson and Lipman. Proc. Natl. Acad. Sci. USA (1998) 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group., Madison. WI), or by manual alignment and visual inspection (see, e.g., Brent et al., Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (Ringbou ed., 2003)). Two examples of algorithms that are suitable for determining sequence identity and sequence similarity (percent) are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., Nuc. Acids Res. (1977) 25:3389-3402 and Altschul et al., J. Mol. Biol. (1990) 215:403-410, respectively.

[0235] In one aspect, the disclosure provides compositions (e.g., compositions A-J) comprising multiple purified strains. For example, Figures 1, 13, 19 and 26 show several exemplary compositions comprising multiple strains. In one aspect, the 16S rDNA sequences of the purified strains of the composition were compared to 16S rDNA sequences of known bacterial species / strains in bacterial genome databases to identify the closest known related bacterial species to the strains disclosed herein (see, e.g., Table 1). It should be understood that multiple strains of the compositions disclosed herein may have the same closest related bacterial species. In one aspect, the disclosure provides compositions comprising one or more strains or species having a 16S rDNA sequence having homology to the nucleic acid sequence of any one of the sequences provided in SEQ ID NOs: 1-83 and 124-159. In some embodiments, a species having a 16S rDNA sequence having homology to the nucleic acid sequence of any one of the most closely related species to any of the strains described herein corresponds to a strain having a 16S rDNA sequence provided by SEQ ID NOs:84-123.

[0236] In some embodiments, the compositions disclosed herein provide at least one of the strains (e.g., purified strains) described herein. In some embodiments, the compositions comprising at least one strain comprise at least one strain having a 16S rDNA sequence selected from any one of SEQ ID NOs: 1-122 and 124-159. In some embodiments, the compositions comprising at least one strain comprise at least one strain having 97% homology to a 16S rDNA sequence selected from any one of SEQ ID NOs: 1-122 and 124-159.

[0237] In some embodiments, the compositions disclosed herein comprise two or more strains, hi some embodiments, the compositions described herein comprise at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20, or more strains (e.g., purified strains).

[0238] It should be understood that the compositions and methods provided herein can be distinguished from available compositions and methods associated with the treatment of C. difficile infection. For example, it has been proposed that non-toxigenic C. difficile strains (i.e., strains that do not produce C. difficile toxins) can be used to treat C. difficile infection (see, e.g., US 6,635,260). The compositions disclosed herein can be distinguished at least because the compositions described herein do not include non-toxigenic strains of C. difficile. Thus, in some aspects, the compositions of the present application do not include non-toxigenic strains of C. difficile. C. difficile belongs to Clostridium cluster XI. In some aspects, the compositions of the present invention do not include strains that belong to Clostridium cluster XI.

[0239] It is also believed in the art that strains expressing the bile-inducible 7α / β-dehydroxylation operon can be used in the treatment of C. difficile (see, e.g., Buffie et al. Nature (2015) 517:205-208). The bile acid 7a-dihydroxylation catalysis is mediated by the conformation-specific NAD(H)-dependent 3-oxo-Δ 4 -Cholenic acid oxidoreductase mediates bile acid 7-α-dehydroxylation. In some aspects, the compositions provided herein do not mediate bile acid 7-α-dehydroxylation.

[0240] Contrary to what is known in the art, in some embodiments, as shown herein, a combination of strains that do not encode baiCD (or a homolog thereof) or that have one or more mutations resulting in a non-functional BaiCD protein ("baiCD-") are more effective in treating C. difficile infections and / or reducing or inhibiting B toxin production by C. difficile than a combination of strains that have a functional BaiCD protein ("baiCD+"). Thus, in some embodiments, the compositions of strains provided herein are baiCD- (i.e., a combination of bacteria that does not have effective baiCD+ function). In some embodiments, all of the strains of the compositions provided herein are baiCD-. In some embodiments, a majority (i.e., 50% or more) of the strains of the composition are baiCD-. In some embodiments, a majority (i.e., 50% or more) of the strains of the composition are baiCD- and the composition does not have effective BaiCD function. In some embodiments, a minority (i.e., 50% or less) of the strains of the composition are baiCD- and the composition does not have effective BaiCD function. In some embodiments, the strains of the composition are selected based on the absence (or presence) of the baiCD gene or predicted baiCD gene. In some embodiments, the expression of the baiCD gene is prevented or reduced and / or the NAD(H)-dependent 3-oxo-ΔB protein of the BaiCD protein is inhibited. 4 The strain can be modified (e.g., by genetic engineering) to reduce or eliminate choline acid oxidoreductase activity. 4 -cholenic acid oxidoreductase activity can be assessed, for example, by measuring the amount of 7α-dehydroxylated bile acids. In some embodiments, the compositions described herein are characterized in that they are capable of encoding the baiCD operon (baiCD - ) or strains lacking the baiCD function.

[0241] In some aspects, the compositions described herein do not include Clostridium scindens. In some aspects, the compositions described herein do not include Barnesiella intestihominis. In some aspects, the compositions described herein do not include Blautia hansenii. In some aspects, the compositions described herein do not include Pseudoflavinofractor capillosus. In some aspects, the compositions described herein do not include Clostridium scindens, Barnesiella intestihominis, Blautia hansenii, or Pseudoflavinofractor capillosus.

[0242] In some aspects, the compositions provided herein do not include Colinsella aerofaciens. In some aspects, the compositions provided herein do not include Acetovibrio ethanolgignens. In some aspects, the compositions provided herein do not include a strain belonging to Clostridium cluster I. In some aspects, the compositions provided herein do not include Clostridium butyricum. In some aspects, the compositions provided herein do not include Clostridium disporicum. In some aspects, the compositions provided herein do not include a strain belonging to Clostridium cluster XI. In some aspects, the compositions provided herein do not include Clostridium glycolicum. In some aspects, the compositions provided herein do not include Faecalibacterium prausnitzii. In some aspects, the compositions provided herein do not include Turicibacter sanguinis. In some aspects, the compositions provided herein do not include Eubacterium rectale. In some aspects, the compositions provided herein do not include Eubacterium ventriosum. In some aspects, the compositions provided herein do not include Ruminococcus obeum. In some aspects, the compositions provided herein do not include Pseudobutyrivibrio. In some aspects, the compositions provided herein do not include Christensenellaceae. In some aspects, the compositions do not include gram-negative bacteria. In some aspects, the compositions do not include Escherichia coli. In some aspects, the compositions do not include fungi, such as Monilla species.

[0243] In some embodiments of the compositions provided herein, the compositions do not include strains that are resistant to one or more antibiotics. It should be understood that it may be desirable to have a mechanism for removing the bacterial composition provided herein from the subject's body after administration. One such mechanism is removing the bacterial composition by antibiotic treatment. Thus, in some embodiments, the compositions do not include strains that are resistant to one or more antibiotics. In some embodiments, the compositions do not include strains that are resistant to one or more antibiotics selected from the group consisting of penicillin, benzylpenicillin, ampicillin, sulbactam, amoxicillin, clavulanic acid, tazobactam, piperacillin, cefmetazole, vancomycin, imipenem, meropenem, metronidazole, and clindamycin. In some embodiments, the compositions do not include strains that are resistant to vancomycin.

[0244] In some embodiments, the composition includes strains that are sensitive to at least four antibiotics that are effective in humans. In some embodiments, the composition includes strains that are sensitive to at least three antibiotics that are effective in humans. In some embodiments, the composition includes strains that are sensitive to at least two antibiotics that are effective in humans. In some embodiments, the composition includes strains that are sensitive to at least one antibiotic that is effective in humans. In some embodiments, the composition includes only strains that are sensitive to at least four antibiotics that are effective in humans. In some embodiments, the composition includes only strains that are sensitive to at least three antibiotics that are effective in humans. In some embodiments, the composition includes only strains that are sensitive to at least two antibiotics that are effective in humans. In some embodiments, the composition includes strains that are sensitive to at least one antibiotic that is effective in humans. As used herein, "antibiotics that are effective in humans" refers to antibiotics that have been used successfully to treat bacterial infections in humans.

[0245] In some embodiments, the compositions described herein include sporulating and non-sporulating strains. In some embodiments, the compositions described herein include sporulating strains. In some embodiments, the compositions described herein include only sporulating strains. In some embodiments, the compositions described herein include only non-sporulating strains. Sporulating bacteria can exist as spore form (i.e., as spores) or as vegetative growth form (i.e., as vegetative cells). In spore form, bacteria are usually more resistant to environmental conditions (e.g., heat, acid, radiation, oxygen, chemicals, and antibiotics). In contrast, in vegetative or actively growing state, bacteria are more susceptible to such environmental conditions compared to spore form. Generally, bacterial spores can germinate from spore form to vegetative / active growth state under appropriate conditions. For example, bacteria in spore format can germinate when introduced into the intestine.

[0246] In some embodiments, at least one of the strains of the composition (e.g., 1, 2, 3, 4, 5 or more) is a spore-forming bacterium. In some embodiments, at least one of the strains of the composition (e.g., 1, 2, 3, 4, 5 or more) is a spore-forming bacterium. In some embodiments, at least one of the strains of the composition (e.g., 1, 2, 3, 4, 5 or more) is a non-spore-forming bacterium. In some embodiments, at least one of the strains of the composition (e.g., 1, 2, 3, 4, 5 or more) is a vegetative form (as described above, spore-forming bacteria may be a vegetative form). In some embodiments, at least one of the strains of the composition (e.g., 1, 2, 3, 4, 5 or more) is a spore-forming bacterium and at least one of the strains of the composition (e.g., 1, 2, 3, 4, 5 or more) is a vegetative form. In some embodiments, at least one strain believed to be capable of forming spores (i.e., spore formers) is present in the composition in a vegetative form. In some embodiments, at least one strain believed to be capable of forming spores (i.e., spore formers) is present in the composition in both spore and vegetative form.

[0247] In some aspects, the disclosure provides compositions comprising strains that are sporulating strains. In some aspects, the disclosure provides compositions comprising strains that are non-sporulating strains. In some aspects, the disclosure provides compositions comprising strains that are sporulating strains and strains that are non-sporulating strains. In some aspects, the disclosure provides compositions comprising mixtures of strains, where at least 10% of the strains are sporulating strains, where at least 20% of the strains are sporulating strains, where at least 30% of the strains are sporulating strains, where at least 40% of the strains are sporulating strains, where at least 50% of the strains are sporulating strains, where at least 60% of the strains are sporulating strains, where at least 70% of the strains are sporulating strains, where at least 80% of the strains are sporulating strains, where at least 90% of the strains are sporulating strains, where up to 100% of the bacteria are sporulating strains. Whether a strain is a sporulating strain can be determined, for example, by analyzing the genome of the strain for the presence of sporulation genes. However, it should be understood that not all bacteria predicted to encode sporulation genes are capable of forming spores. In addition, whether a strain is a sporulating strain can be determined by exposing the strain to stress conditions known to induce sporulation, such as exposure to heat or chemicals (ethanol or chloroform).

[0248] It should be understood that the spore-forming bacteria may be in spore form or vegetative growth form. In some embodiments of the compositions provided herein, the spore-forming bacteria is in spore form. In some embodiments of the compositions provided herein, the spore-forming bacteria is in vegetative growth form. In some embodiments of the compositions provided herein, the spore-forming bacteria is present in both spore form and vegetative growth form. In some aspects, the disclosure provides compositions comprising a spore-forming strain that is at least 10% in spore format, at least 20% in spore format, at least 30% in spore format, at least 40% in spore format, at least 50% in spore format, at least 60% in spore format, at least 70% in spore format, at least 80% in spore format, at least 90% in spore format, up to 100% in spore format.

[0249] The strains of the compositions provided herein are alive and are assumed to be alive when they reach the target site (e.g., the intestine). Bacterial spores are considered alive in this respect. In some embodiments, bacteria administered as spores can germinate at the target site (e.g., the intestine). It should be further understood that not all bacteria are alive and the composition may include a percentage (e.g., by weight) of bacteria that are not alive. In addition, in some embodiments, the composition includes strains that are not alive when administered or when the composition reaches the target site (e.g., the intestine). It is assumed that dead bacteria may still be useful by providing some nutrients and metabolic products to other strains in the composition. Methods for inducing sporulation in sporulating strains are well known in the art (see, for example, Paredes-Sabja et al., Trends Microbiol. (2011) 19(2):85-94). Generally, strains that are sporulating can be made to undergo sporulation by subjecting the strain to stress. Non-limiting examples of stresses that can induce sporulation are elevated temperature, changes in nutrient availability, and / or exposure to chemicals (e.g., ethanol or chloroform). It should be noted that bacteria that are non-sporulating, e.g., because they lack sporulation genes, cannot be made to sporulate by stress. To prepare a composition in which all strains are in sporulation, the composition or bacterial culture used to prepare the composition can be subjected to a treatment to kill any bacteria that are not in sporulation (e.g., in vegetative growth form), e.g., by heating the composition and chemically decomposing the non-sporulating bacteria. The sporulating bacteria can then be separated from the non-sporulating bacteria, e.g., by filtration.

[0250] The amount of spores can be quantified using methods known in the art. These methods include counting spores under phase contrast microscopy using a hemocytometer. In addition, spore viability can be determined by plating the spores and growing them. For example, spores can be plated on a suitable medium and incubated in a chamber under anaerobic conditions for a given time (e.g., 48-96 hours). Viability can then be determined by quantifying the colony forming units corresponding to the germinated spores. For example, spores can be plated on TCCFA plates (taurocholate, cycloserine, cefoxintin, fructose-containing agar plates), where taurocholate promotes spore germination. In addition, spores can be quantified using the dipicolinic acid assay (DPA assay). DPA is an agent that allows for the selection of spores and is a clear indicator of endospores. When complexed with terbium, a bright green luminescence is observed.

[0251] In any of the compositions provided herein, in some embodiments, the strain is purified. In any of the compositions provided herein, in some embodiments, the strain is isolated. Any of the strains described herein can be isolated and / or purified from a source, such as, for example, a culture medium or a microbiota sample (e.g., feces). The strains used in the compositions provided herein are generally isolated from the microbiome of a healthy individual. However, the strains may also be isolated from an individual considered to be unhealthy. In some embodiments, the composition comprises strains from multiple individuals.

[0252] As used herein, the term "isolated" refers to bacteria that have been separated from one or more undesirable components (e.g., other bacteria or strains), one or more components of the growth medium, and / or one or more components in a sample (e.g., a fecal sample). In some embodiments, the bacteria are substantially isolated from a source such that other components in the source are undetectable.

[0253] The term "purified" in this application also refers to a strain or a composition comprising the same being separated from one or more components (e.g., contaminants). In some embodiments, the strain is substantially contaminant-free. In some embodiments, one or more strains of a composition can be purified independently from one or more other strains occurring and / or present in a culture or sample comprising the bacteria. In some embodiments, the strain is isolated or purified from a sample and then cultured under conditions suitable for bacterial replication, such as anaerobic culture conditions. The bacteria grown under conditions suitable for bacterial replication can then be isolated / purified from the medium in which they were grown.

[0254] In some aspects, the strains of the compositions provided herein are obligate anaerobes. In some aspects, the strains of the compositions provided herein are facultative anaerobes.

[0255] Aspects of the present disclosure relate to a method of treating a pathogen infection in a subject by administering a therapeutically effective amount of any of the compositions described herein. In some aspects, the subject is a mammalian subject, such as a human, non-human primate, rodent, rabbit, sheep, pig, dog, cat, horse, or cow. In some aspects, the subject is a human subject. In some aspects, the subject is a pig. In some embodiments, the subject is a carrier of a pathogen and is suffering from the effects of the infection (e.g., diarrhea caused by C. difficile toxins). In some embodiments, the subject is an asymptomatic carrier of a pathogen. In some embodiments, the subject is a carrier of C. difficile. In some embodiments, the subject is an asymptomatic carrier of C. difficile. In some embodiments, the subject is experiencing a recurrent or chronic pathogen infection. In some embodiments, the subject is suffering from a primary specific pathogen infection. In some embodiments, the subject is suffering from a recurrent pathogen infection as a result of treatment with an antibiotic. In some embodiments, the subject is suffering from a primary pathogen infection as a result of treatment with an antibiotic. In some embodiments, the subject is undergoing a treatment that increases the subject's risk of infection. In some embodiments, the compositions provided herein are administered to the subject to reduce the risk of infection by a pathogen.

[0256] In some aspects, the compositions provided herein are administered to a subject when the subject has a dysbiosis (e.g., has a microbiome associated with a disease state). In some aspects, treatment with the compositions provided herein results in a change in the subject's microbiome. In some aspects, treatment with the compositions provided herein removes the subject's dysbiosis, resulting in a healthy microbiome. In some aspects, treatment with the compositions provided herein removes the subject's dysbiosis, resulting in an increased resistance or decreased susceptibility to infection by a pathogen of the microbiome.

[0257] As used herein, the term "pathogen" in reference to a pathogen infection refers to a microorganism (e.g., bacteria) that causes a disease or disease state in a subject. In some embodiments, the disease or disease state in a subject may include symptoms such as colitis, diarrhea, watery stool, abdominal cramps, fever, blood or pus in the stool, nausea, dehydration, loss of appetite, intolerance to cold, weight loss, and / or renal failure. In some embodiments, a pathogen infection can be diagnosed, for example, by detecting the pathogen (or a protein or nucleic acid associated with the pathogen) in a stool sample collected from a subject. In some embodiments, a pathogen infection can be diagnosed, for example, by comparing the microbiota in a stool sample from a healthy individual with the microbiota in a stool sample from a subject.

[0258] In some embodiments, the pathogen infection is selected from the group consisting of C. difficile, Clostridium perfringens, Clostridium botulinum, Clostridium tributrycum, Clostridium sporogenes, Escherichia coli, Pseudomonas aeruginosa (e.g., multidrug-resistant Pseudomonas aeruginosa), vancomycin-resistant Enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), Neisseria gonorrhea, Acinetobacter, multidrug-resistant Acinetobacter, Campylobacter, multidrug-resistant Campylobacter, Candida, fluconazole-resistant Candida, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, Salmonella, Salmonella Typhimurium, drug-resistant non-typhoidal Salmonella spp., drug-resistant Salmonella In some embodiments, the pathogen infection is caused by C. difficile. In some embodiments, the C. difficile is antibiotic-resistant C. difficile, e.g., fluoroquinolone-resistant C. difficile. In some embodiments, the pathogen infection is vancomycin-resistant Enterococci.

[0259] With a slightly less expensive background, you can find a range of snowflakes One of the main organisms is Leishmania, Staphylococcus epidermis、Staphylococcus saprophyticus、Streptococcus pyogenes、Streptococcus pneumoniae、Streptococcus agalactiae、Enterococcus faecalis、Corynebacterium diptheriae、Bacillus anthracis、Listeria monocytogenes Clostridium perfringens Clostridium tetanus Clostridium botulinum Clostridium difficile Neisseria meningitidis Neisseria gonorrhoeae Escherichia coli Salmonella typhimurium Salmonella cholerasui Salmonella enterica、Salmonella enteriditis、Yersinia pestis、Yersinia pseudotuberculosis、Yersinia enterocolitica、Vibrio cholerae、Campylobacter jejuni、Campylobacter fetus、Helicobacter pylori、Pseudomonas aeruginosa、Pseudomonas mallei、Haemophilus influenzae、Bordetella pertussis、Mycoplasma pneumoniae、Ureaplasma urealyticum、Legionella pneumophila、Treponema pallidum、Leptospira interrogans、Borrelia burgdorferi、Mycobacterium tuberculosis、Mycobacterium leprae、Chlamydia psittaci、Chlamydia trachomatis、Chlamydia pneumoniae、RickettsiaThe following bacteria are considered pathogens: Brucella ricketsii, Rickettsia akari, Rickettsia prowazekii, Brucella abortus, Brucella melitens, Brucella suis and Francisella tularensis. In general, any bacteria that can induce disease in a subject and / or that is not present in healthy individuals shall be considered a pathogen herein. It should be understood that a subject may carry multiple pathogens and / or suffer from multiple pathogen infections.

[0260] Any of the compositions described herein can be administered to a subject in a therapeutically effective amount or dose to treat or prevent a pathogen infection (e.g., one or more pathogen infections). The term "treat" or "treatment" refers to alleviating or alleviating one or more symptoms associated with a pathogen infection, reducing the amount of bacterial toxins produced by a pathogen infection, and / or reducing the amount of bacteria caused by a pathogen infection. The term "prevent" or "prevention" may encompass prophylactic administration and may refer to reducing the incidence or likelihood of a pathogen infection or a recurrent or chronic pathogen infection. For example, in some embodiments, administration of a composition provided herein results in a healthy microbiome that is less susceptible to pathogen infection, thereby preventing pathogen infection.

[0261] A "therapeutically effective amount" of a composition (e.g., a pharmaceutical composition) described herein is any amount that results in a desired response or outcome in a subject, such as those described herein, including, but not limited to, prevention of infection, immune response or enhanced immune response to a pathogenic infection, prevention or reduction of symptoms associated with a pathogenic infection, and / or reduction or inhibition of toxin production by a pathogenic infection. It should be understood that the term "effective amount" can be expressed as the number of bacteria or bacterial spores administered. It should also be understood that bacteria may divide once administered. Thus, administration of even a relatively small amount of bacteria may have a therapeutic effect.

[0262] In some embodiments, a therapeutically effective amount of any of the compositions described herein is an amount sufficient to improve survival in a subject, reduce the bacterial load of a pathogen infection in a subject, and / or reduce or inhibit toxin production by a pathogen infection. In some embodiments, a therapeutically effective amount is an amount sufficient to increase survival in a subject, reduce the bacterial load of a pathogen infection in a subject, and / or reduce or inhibit toxin production by a pathogen infection. In some embodiments, a therapeutically effective amount is an amount sufficient to increase survival in a subject, reduce the bacterial load of a pathogen infection in a subject, and / or reduce or inhibit toxin production by a pathogen infection. In some embodiments, a therapeutically effective amount is an amount sufficient to increase survival in a subject, reduce the bacterial load of a pathogen infection in a subject that has not received any of the compositions described herein, or ... 4 Double, 10 5 fold or more, sufficient to reduce the bacterial load of a pathogenic infection in a stool sample from the subject.

[0263] In some embodiments, the compositions provided herein inhibit the production of bacterial toxins (e.g., B toxin of C. difficile). In some embodiments, a therapeutically effective amount is an amount sufficient to reduce the amount of bacterial toxins in a fecal sample from a subject by at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 150-fold, 200-fold, 500-fold or more compared to the amount of bacterial toxins (e.g., B toxin of C. difficile) in a pathogen-infected subject that has not received any of the compositions described herein, or compared to the amount of bacterial toxins in a fecal sample from the same subject collected prior to administration of any of the compositions.

[0264] In some embodiments, the compositions provided herein induce the proliferation and / or accumulation of regulatory T cells in a subject.As is clear to those skilled in the art, regulatory T cells (also referred to as "Treg") are a subset of T lymphocytes that are generally believed to suppress abnormal or excessive immune responses and play a role in immune tolerance.Regulatory T cells may be identified based on the expression of markers Foxp3 and CD4 (Foxp3+CD4+).The term regulatory T cells may also include Foxp3-negative regulatory T cells, which are IL-10-producing CD4-positive T cells.

[0265] In some embodiments, a therapeutically effective amount is an amount sufficient to induce at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 150-fold, 200-fold, 500-fold or more proliferation and / or accumulation of Tregs in a subject (or a sample obtained from a subject) compared to the amount of Tregs in a subject (e.g., a subject suffering from a pathogen infection) that has not received a composition described herein, or compared to a stool sample from the same subject collected prior to administration of the composition.

[0266] As used herein, the term "inducing proliferation and / or accumulation of regulatory T cells" refers to the effect of inducing differentiation of immature T cells into regulatory T cells, which differentiation results in proliferation and / or accumulation of regulatory T cells. Furthermore, the meaning of "inducing proliferation and / or accumulation of regulatory T cells" encompasses in vivo effects, in vitro effects, and ex vivo effects. In some embodiments, the proliferation and / or accumulation of regulatory T cells can be calculated by detecting cells expressing markers of regulatory T cells (e.g., Foxp3 and CD4) and / or quantifying cell number (e.g., by flow cytometry). In some embodiments, the proliferation and / or accumulation of regulatory T cells can be calculated by measuring the activity of regulatory T cells, such as the production of cytokines (e.g., IL-10).

[0267] In some embodiments, a therapeutically effective amount is an amount sufficient to recolonize or repopulate the subject's digestive tract with non-pathogenic bacteria. In some embodiments, a therapeutically effective amount is an amount sufficient to graft one or more strains of the composition into the digestive tract of the subject. In some embodiments, a fecal sample is collected from the subject to assess the bacterial burden of a pathogen infection and / or evaluate the efficacy of administration of the bacterial composition described herein. In some embodiments, the subject's microbiota (e.g., the identity and abundance of the strains and / or species of the microbiota) can be evaluated to determine the subject's disease state and / or assess the progress of treatment. In some embodiments, the microbiota of a subject with a pathogen infection is compared to the microbiota of a healthy subject, e.g., a subject that does not or has not experienced a pathogen infection. In some embodiments, the microbiota of a subject with a pathogen infection is compared to the microbiota of a fecal sample obtained from the same subject before the subject contracted the pathogen infection.

[0268] Any of the compositions described herein, including pharmaceutical compositions and food products containing the compositions, may contain the strains, for example, in an aqueous form, such as a solution or suspension, embedded in a semi-solid form, in a powder form or in a lyophilized form. In some embodiments, the composition or the strains of the composition are lyophilized. In some embodiments, a subset of the strains in the composition are lyophilized. Methods for lyophilizing compositions, particularly compositions containing bacteria, are well known in the art. See, for example, US 3,261,761, US 4,205,132, PCT Publications WO2014 / 029578 and WO2012 / 098358, the contents of which are incorporated herein by reference in their entirety. The bacteria may be lyophilized in combination and / or may be lyophilized separately and then combined prior to administration. The strains may be combined with a pharmaceutical excipient prior to combination with other strains, or multiple lyophilized bacteria may be combined in lyophilized form and the bacteria combined as a mixture prior to combination with a pharmaceutical excipient. In some embodiments, the strains are a lyophilized cake. In some embodiments, the composition comprising one or more strains is a lyophilized cake.

[0269] The bacterial strains of the composition can be produced using fermentation techniques well known in the art. In some embodiments, the active ingredients are produced using anaerobic fermenters, which can support the rapid growth of anaerobic bacterial species. The anaerobic fermenters can be, for example, stirred tank reactors or disposable wave bioreactors. Culture media (e.g., BL and EG media) or similar versions of these media without animal components can be used to support the growth of the bacterial species. The bacterial products can be purified and concentrated from the fermentation broth by conventional techniques (e.g., centrifugation and filtration) and can be optionally dried and lyophilized by techniques well known in the art.

[0270] In some embodiments, the composition of the strains may be formulated for administration as a pharmaceutical composition. As used herein, the term "pharmaceutical composition" refers to a product resulting from the mixing or combination of at least one active ingredient (e.g., any two or more purified strains described herein) and one or more inactive ingredients, which may include one or more pharmacologically acceptable excipients.

[0271] An "acceptable" excipient refers to an excipient that must be compatible with the active ingredient and not harmful to the subject to which it is administered. In some aspects, the pharmacologically acceptable excipient is selected based on the intended route of administration of the composition, for example, a composition for oral or nasal administration may contain different pharmacologically acceptable excipients than a composition for rectal administration. Excipients include sterile water, physiological saline, solvents, base materials, emulsifiers, suspending agents, surfactants, stabilizers, flavors, fragrances, excipients, vehicles, preservatives, binders, diluents, isotonicity agents, soothing agents, fillers, disintegrants, buffers, coating agents, lubricants, colorants, sweeteners, thickeners, and solubilizers.

[0272] The pharmaceutical compositions of the present invention can be prepared according to routinely practiced methods well known in the art (see, for example, Remington: The Science and Practice of Pharmacy, Mack Publishing Co. 20th ed. 2000). The pharmaceutical compositions described herein may further comprise any carrier or stabilizer in the form of a lyophilized formulation or an aqueous solution. Acceptable excipients, carriers or stabilizers may include, for example, buffers, antioxidants, preservatives, polymers, chelating agents and / or surfactants. The pharmaceutical compositions are preferably manufactured under GMP conditions. The pharmaceutical compositions may be used for oral, intranasal or parenteral administration, for example in the form of capsules, tablets, pills, sachets, liquids, powders, granules, fine granules, film coated preparations, pellets, troches, sublingual preparations, chewable, buccal preparations, pastes, syrups, suspensions, elixirs, emulsions, salves, ointments, bandages, poultices, transdermal systems, lotions, inhalants, aerosols, injections, suppositories, and the like.

[0273] In some embodiments, the bacteria are formulated for delivery to the intestine (e.g., the small intestine and / or colon). In some embodiments, the bacteria are formulated with an enteric coating that enhances the survival of the bacteria in the harsh environment of the stomach. The enteric coating is resistant to the action of gastric juice in the stomach, thereby allowing the bacteria incorporated therein to pass from the stomach to the intestine. Upon contact with intestinal juice, the enteric coating can be easily dissolved, resulting in the release of the bacteria encapsulated within the coating into the intestinal tract. The enteric coating can be made of polymers and copolymers known in the art, such as the commercially available EUDRAGIT (Evonik Industries). (See, e.g., Zhang, AAPS PharmSciTech, (2016) 17 (1), 56-67).

[0274] The bacteria may also be formulated for delivery through the rectum into the intestine (e.g., colon). Thus, in some embodiments, the bacterial composition may be formulated for delivery by suppository, colonoscope, endoscope, sigmoidoscope, or enema. The pharmaceutical preparation or formulation, particularly the formulation for oral administration, may include additional components that allow for efficient delivery of the composition according to the present disclosure to the intestine (e.g., colon). Various pharmaceutical preparations that allow for delivery of the composition to the intestine (e.g., colon) can be used. Examples include pH-sensitive compositions, more specifically buffered sachets or enteric polymers that release their contents when the pH becomes alkaline after the enteric polymer has passed through the stomach. When a pH-sensitive composition is used to formulate the pharmaceutical preparation, the pH-sensitive composition is preferably a polymer with a pH threshold for degradation of the composition between about 6.8 and about 7.5. Such a numerical range is the range in which the pH shifts to the alkaline side at the distal part of the stomach, and is therefore a suitable range for use in delivery to the colon. Furthermore, it should be understood that each part of the intestine (e.g., duodenum, jejunum, ileum, cecum, colon and rectum) has a different biochemical and chemical environment. For example, different parts of the intestine have different pHs, and compositions with specific pH sensitivity can provide target-specific delivery. Thus, the compositions provided herein can be formulated for delivery to the intestine or specific parts of the intestine (e.g., duodenum, jejunum, ileum, cecum, colon and rectum) by providing suitable pH-sensitive formulations (see, for example, Villena et al., Int JP harm 2015, 487 (1-2): 314-9).

[0275] Another embodiment of the pharmaceutical preparation useful for delivery of compositions to the intestine (e.g., colon) ensures delivery to the colon by delaying the release of the contents (e.g., strains) for about 3-5 hours, which corresponds to the transit time in the small intestine. In one embodiment of the pharmaceutical preparation for delayed release, a hydrogel is used as the shell. The hydrogel hydrates and expands upon contact with the body fluids in the gastrointestinal tract, resulting in effective release of the contents (mainly in the colon). Dosage units for delayed release include drug-containing compositions having materials that coat or selectively coat the drug or active ingredient to be administered. Examples of such selective coating materials include in vivo degradable polymers, stepwise hydrolyzable polymers, stepwise water-soluble polymers and / or enzymatically degradable polymers. A wide variety of coating materials are available for efficient delayed release, including, for example, cellulosic polymers such as hydroxypropylcellulose, acrylic polymers and copolymers such as methacrylic acid polymers and copolymers, and vinylic polymers and copolymers such as polyvinylpyrrolidone.

[0276] Additional examples of pharmaceutical compositions that allow for delivery to the intestine (e.g., colon) include bioadhesive compositions that specifically adhere to the colonic mucosa (e.g., the polymers described in U.S. Pat. No. 6,368,586) and compositions that incorporate protease inhibitors to protect biopharmaceutical preparations in the gastrointestinal tract, particularly from degradation due to protease activity.

[0277] Another example of a system that enables delivery to the intestine (e.g., colon) is a system that delivers a composition to the colon by pressure change, such as a system that utilizes air pressure changes caused by gas generation due to fermentation of bacteria in the distal part of the stomach to release the contents. Such a system is not particularly limited, and a more specific example thereof is a capsule having the contents dispersed in a suppository base and coated with a hydrophobic polymer (e.g., ethyl cellulose).

[0278] Further examples of systems that allow for delivery of a composition to the intestine (e.g., colon) are compositions that include a coating that can be removed by enzymes (e.g., carbohydrate hydrolases or carbohydrate reductases) present in the digestive tract (e.g., colon). Such systems are not particularly limited, and more specific examples include systems that use food ingredients such as non-starch polysaccharides, amylose, xanthan gum, and azopolymers.

[0279] The compositions provided herein can also be delivered to specific target sites (e.g., intestines) by delivery through opening (e.g., nasogastric tube) or through surgery.In addition, the compositions provided herein that are formulated for delivery to specific sites (e.g., cecum or colon) can be administered by tube (e.g., directly to the small intestine).Mechanical delivery methods such as tubes can also be combined with chemical delivery methods such as pH-specific coating to deliver the compositions provided herein to desired target sites (e.g., cecum or colon).

[0280] The composition comprising the strain is formulated into a pharmacologically acceptable dosage form by conventional methods known to those skilled in the art. The dosage regimen is adjusted to provide the optimum desired response (e.g., prophylactic or therapeutic effect). In some embodiments, the composition is in the form of a tablet, pill, capsule, powder, granule, solution, or suppository. In some embodiments, the pharmaceutical composition is formulated for oral administration. In some embodiments, the pharmaceutical composition is formulated such that the bacteria or a portion thereof in the composition remains viable after passing through the stomach of the subject. In some embodiments, the pharmaceutical composition is formulated for rectal administration, for example, as a suppository. In some embodiments, the pharmaceutical composition is formulated for delivery to the intestine or a specific site in the intestine (e.g., colon) by providing an appropriate coating (e.g., a pH-specific coating, a coating that is degraded by a target site-specific enzyme, or a coating that can bind to a receptor present at the target site).

[0281] The dosage of the active ingredient in the pharmaceutical composition of the present invention can be varied to provide an effective amount of the active ingredient to obtain the desired drug response in a particular subject, composition and mode of administration, without being toxic or adversely affecting the subject. The selection of dosage level depends on a variety of factors, such as the activity of the particular composition of the present invention employed, the route of administration, the time of administration, the duration of treatment, other drugs, compounds and / or materials used in combination with the particular composition employed, the age, sex, weight, condition, general health and medical history of the subject to be treated.

[0282] A physician, veterinarian, or other trained practitioner may begin administering the pharmaceutical composition at a level lower than that required to achieve the desired therapeutic effect, and gradually increase the dose until the desired effect (e.g., treatment of a pathogen infection, reduction of the bacterial load of a pathogen infection, reduction or inhibition of toxin production) is achieved. In general, the effective dose of the compositions of the present invention, in the case of prophylactic treatment of a group of humans as described herein, will vary depending on many different factors, such as the route of administration, the physiological state of the subject, whether the subject is human or animal, other drugs administered, and the therapeutic effect desired. The dose needs to be titrated to optimize safety and efficacy. In some embodiments, the administration regimen involves oral administration of a dose of any of the compositions described herein. In some embodiments, the administration regimen involves oral administration of multiple doses of any of the compositions described herein. In some embodiments, the composition is orally administered to the subject one, three, four, five, six, seven, eight, nine, or at least ten times.

[0283] Compositions, including pharmaceutical compositions, disclosed herein include compositions that contain various active ingredients (e.g., live bacteria, bacteria in spore format). The amount of bacteria in the composition can be expressed by weight, number of bacteria, and / or CFU (colony forming units). In some embodiments, the pharmaceutical compositions disclosed herein contain each bacterium of the composition in an amount of about 10, about 10 per dose ... 2 , about 10 3 , about 10 4 , about 10 5 , about 106 , about 10 7 , about 10 8 , about 10 9 , about 10 10 , about 10 11 , about 10 12 , about 10 13 In some embodiments, the pharmaceutical compositions disclosed herein contain about 10, about 10 total bacteria per dose. 2 , about 10 3 , about 10 4 , about 10 5 , about 10 6 , about 10 7 , about 10 8 , about 10 9 , about 10 10 , about 10 11 , about 10 12 , about 10 13 It should be further understood that the bacteria of the composition may be present in different amounts. That is, for example and as a non-limiting example, the composition may contain 10 or more bacteria A. 3 10 pieces of bacteria B 4 10 pieces, and bacteria C 6 In some embodiments, the pharmaceutical compositions disclosed herein may contain about 10, about 10 of each bacterium in the composition per dose. 2 , about 10 3 , about 10 4 , about 10 5 , about 10 6 , about 10 7 , about 10 8 , about 10 9 , about 10 10 , about 10 11 , about 10 12 , about 10 13 In some embodiments, the pharmaceutical compositions disclosed herein contain at least about 10 total bacteria in a mixture per dose. 1 , about 10 2 , about 103, about 10 4 , about 10 5 , about 10 6 , about 10 7 , about 10 8 , about 10 9 , about 10 10 , about 10 11 , about 1012 , about 10 13 As noted above, the bacteria of the composition may be present in different amounts. In some embodiments, the pharmaceutical compositions disclosed herein contain each bacterium of the composition at about 10 CFU per dose. -7 , about 10 -6 , about 10 -5 , about 10 -4 , about 10 -3 , about 10 -2 , about 10 -1 In some embodiments, the pharmaceutical compositions disclosed herein contain more than about 10 g of total bacteria per dose. -7 , about 10 -6 , about 10 -5 , about 10 -4 , about 10 -3 , about 10 -2 , about 10 -1 In some embodiments, a dose is the amount in one administration device (e.g., one tablet, pill, or capsule). In some embodiments, a dose is the amount administered in a particular period (e.g., one day or one week).

[0284] In some embodiments, the pharmaceutical compositions disclosed herein contain between 10 and 10 13 , 10 2 ~10 13 , 10 3 ~10 13 , 10 4 ~10 13 , 10 5 ~10 13 , 10 6 ~10 13 , 10 7 ~10 13 , 10 8 ~10 13 , 10 9 ~10 13 , 10 10 ~10 13 , 10 11 ~10 13 , 10 12 ~10 13 , 10~10 12 , 10 2 ~10 12、10 3 ~10 12 、10 4 ~10 12 、10 5 ~10 12 、10 6 ~10 12 、10 7 ~10 12 、10 8 ~10 12 、10 9 ~10 12 、10 10 ~10 12 、10 11 ~10 12 、10~10 11 、10 2 ~10 11 、10 3 ~10 13 、10 4 ~10 13 、10 5 ~10 13 、10 6 ~10 13 、10 7 ~10 11 、10 8 ~10 11 、10 9 ~10 11 、10 10 ~10 11 、10~10 10 、10 2 ~10 10 、10 3 ~10 10 、10 4 ~10 10 、10 5 ~10 10 、10 6 ~10 10 、10 7 ~10 10 、10 8 ~10 10 、10 9 ~10 10 、10~10 9 、10 2 ~10 9 、10 3 ~10 9 、10 4 ~10 9 、10 5~10 9 , 10 6 ~10 9 , 10 7 ~10 9 , 10 8 ~10 9 , 10~10 8 , 10 2 ~10 8 , 10 3 ~10 8 , 10 4 ~10 8 , 10 5 ~10 8 , 10 6 ~10 8 , 10 7 ~10 8 , 10~10 7 , 10 2 ~10 7 , 10 3 ~10 7 , 10 4 ~10 7 , 10 5 ~10 7 , 10 6 ~10 7 , 10~10 6 , 10 2 ~10 6 , 10 3 ~10 6 , 10 4 ~10 6 , 10 5 ~10 6 , 10~10 5 , 10 2 ~10 5 , 10 3 ~10 5 , 10 4 ~10 5 , 10~10 4 , 10 2 ~10 4 , 10 3 ~10 4 , 10~10 3 , 10 2 ~10 3 Or 10 to 10 2 In some embodiments, the pharmaceutical compositions disclosed herein contain between 10 and 10 total bacteria per dose. 13 , 10 2 ~1013 、10 3 ~10 13 、10 4 ~10 13 、10 5 ~10 13 、10 6 ~10 13 、10 7 ~10 13 、10 8 ~10 13 、10 9 ~10 13 、10 10 ~10 13 、10 11 ~10 13 、10 12 ~10 13 、10~10 12 、10 2 ~10 12 、10 3 ~10 12 、10 4 ~10 12 、10 5 ~10 12 、10 6 ~10 12 、10 7 ~10 12 、10 8 ~10 12 、10 9 ~10 12 、10 10 ~10 12 、10 11 ~10 12 、10~10 11 、10 2 ~10 11 、10 3 ~10 13 、10 4 ~10 13 、10 5 ~10 13 、10 6 ~10 13 、10 7 ~10 11 、10 8 ~10 11 、10 9 ~10 11 、10 10 ~10 11 、10~10 10 、102 ~10 10 、10 3 ~10 10 、10 4 ~10 10 、10 5 ~10 10 、10 6 ~10 10 、10 7 ~10 10 、10 8 ~10 10 、10 9 ~10 10 、10~10 9 、10 2 ~10 9 、10 3 ~10 9 、10 4 ~10 9 、10 5 ~10 9 、10 6 ~10 9 、10 7 ~10 9 、10 8 ~10 9 、10~10 8 、10 2 ~10 8 、10 3 ~10 8 、10 4 ~10 8 、10 5 ~10 8 、10 6 ~10 8 、10 7 ~10 8 、10~10 7 、10 2 ~10 7 、10 3 ~10 7 、10 4 ~10 7 、10 5 ~10 7 、10 6 ~10 7 、10~10 6 、10 2 ~10 6 、10 3 ~10 6 、10 4 ~10 6, 10 5 ~10 6 , 10~10 5 , 10 2 ~10 5 , 10 3 ~10 5 , 10 4 ~10 5 , 10~10 4 , 10 2 ~10 4 , 10 3 ~10 4 , 10~10 3 , 10 2 ~10 3 Or 10 to 10 2 Contains pieces.

[0285] In some embodiments, the pharmaceutical compositions disclosed herein contain between 10 and 10 13 , 10 2 ~10 13 , 10 3 ~10 13 , 10 4 ~10 13 , 10 5 ~10 13 , 10 6 ~10 13 , 10 7 ~10 13 , 10 8 ~10 13 , 10 9 ~10 13 , 10 10 ~10 13 , 10 11 ~10 13 , 10 12 ~10 13 , 10~10 12 , 10 2 ~10 12 , 10 3 ~10 12 , 10 4 ~10 12 , 10 5 ~10 12 , 10 6 ~10 12 , 10 7 ~10 12 , 10 8 ~10 12、10 9 ~10 12 、10 10 ~10 12 、10 11 ~10 12 、10~10 11 、10 2 ~10 11 、10 3 ~10 13 、10 4 ~10 13 、10 5 ~10 13 、10 6 ~10 13 、10 7 ~10 11 、10 8 ~10 11 、10 9 ~10 11 、10 10 ~10 11 、10~10 10 、10 2 ~10 10 、10 3 ~10 10 、10 4 ~10 10 、10 5 ~10 10 、10 6 ~10 10 、10 7 ~10 10 、10 8 ~10 10 、10 9 ~10 10 、10~10 9 、10 2 ~10 9 、10 3 ~10 9 、10 4 ~10 9 、10 5 ~10 9 、10 6 ~10 9 、10 7 ~10 9 、10 8 ~10 9 、10~10 8 、10 2 ~10 8 、10 3 ~108 , 10 4 ~10 8 , 10 5 ~10 8 , 10 6 ~10 8 , 10 7 ~10 8 , 10~10 7 , 10 2 ~10 7 , 10 3 ~10 7 , 10 4 ~10 7 , 10 5 ~10 7 , 10 6 ~10 7 , 10~10 6 , 10 2 ~10 6 , 10 3 ~10 6 , 10 4 ~10 6 , 10 5 ~10 6 , 10~10 5 , 10 2 ~10 5 , 10 3 ~10 5 , 10 4 ~10 5 , 10~10 4 , 10 2 ~10 4 , 10 3 ~10 4 , 10~10 3 , 10 2 ~10 3 Or 10 to 10 2 In some embodiments, the pharmaceutical compositions disclosed herein contain 10 to 10 CFU per dose. 13 , 10 2 ~10 13 , 10 3 ~10 13 , 10 4 ~10 13 , 10 5 ~10 13 , 10 6 ~10 13 , 10 7 ~10 13 , 10 8~10 13 、10 9 ~10 13 、10 10 ~10 13 、10 11 ~10 13 、10 12 ~10 13 、10~10 12 、10 2 ~10 12 、10 3 ~10 12 、10 4 ~10 12 、10 5 ~10 12 、10 6 ~10 12 、10 7 ~10 12 、10 8 ~10 12 、10 9 ~10 12 、10 10 ~10 12 、10 11 ~10 12 、10~10 11 、10 2 ~10 11 、10 3 ~10 13 、10 4 ~10 13 、10 5 ~10 13 、10 6 ~10 13 、10 7 ~10 11 、10 8 ~10 11 、10 9 ~10 11 、10 10 ~10 11 、10~10 10 、10 2 ~10 10 、10 3 ~10 10 、10 4 ~10 10 、10 5 ~10 10 、10 6 ~10 10 、10 7 ~10 10、10 8 ~10 10 、10 9 ~10 10 、10~10 9 、10 2 ~10 9 、10 3 ~10 9 、10 4 ~10 9 、10 5 ~10 9 、10 6 ~10 9 、10 7 ~10 9 、10 8 ~10 9 、10~10 8 、10 2 ~10 8 、10 3 ~10 8 、10 4 ~10 8 、10 5 ~10 8 、10 6 ~10 8 、10 7 ~10 8 、10~10 7 、10 2 ~10 7 、10 3 ~10 7 、10 4 ~10 7 、10 5 ~10 7 、10 6 ~10 7 、10~10 6 、10 2 ~10 6 、10 3 ~10 6 、10 4 ~10 6 、10 5 ~10 6 、10~10 5 、10 2 ~10 5 、10 3 ~10 5 、10 4 ~10 5 、10~10 4 、10 2 ~104 , 10 3 ~10 4 , 10~10 3 , 10 2 ~10 3 Or 10 to 10 2 Contains total CFU of In some embodiments, the pharmaceutical compositions disclosed herein contain at least 10 of each bacterium in the composition per dose. -7 ~10 -1 , 10 -6 ~10 -1 , 10 -5 -10 -1 , 10 -4 ~10 -1 , 10 -3 ~10 -1 , 10 -2 ~10 -1 , 10 -7 -10 -2 , 10 -6 ~10 -2 , 10 -5 ~10 -2 , 10 -4 ~10 -2 , 10 -3 -10 -2 , 10 -7 ~10 -3 , 10 -6 ~10 -3 , 10 -5 ~10 -3 , 10 -4 -10 -3 , 10 -7 ~10 -4 , 10 -6 ~10 -4 , 10 -5 ~10 -4 , 10 -7 -10 -5 , 10 -6 ~10 -5 or 10 -7 ~10 -6 In some embodiments, the pharmaceutical compositions disclosed herein contain more than 10 g of the combined total bacteria per dose. -7 ~10 -1 , 10 -6 ~10 -1 , 10 -5 ~10 -1 , 10-4 ~10 -1 , 10 -3 ~10 -1 , 10 -2 ~10 -1 , 10 -7 ~10 -2 , 10 -6 ~10 -2 , 10 -5 ~10 -2 , 10 -4 ~10 -2 , 10 -3 ~10 -2 , 10 -7 ~10 -3 , 10 -6 ~10 -3 , 10 -5 ~10 -3 , 10 -4 ~10 -3 , 10 -7 ~10 -4 , 10 -6 ~10 -4 , 10 -5 ~10 -4 , 10 -7 ~10 -5 , 10 -6 ~10 -5 or 10 -7 ~10 -6 Contains g.

[0286] Also within the scope of this disclosure is a food product that includes any of the strains described herein and nutrients. Food products are generally intended for human or animal consumption. Any of the strains described herein can be formulated as a food product. In some embodiments, the strains are formulated as a food product in spore form. In some embodiments, the strains are formulated as a food product in vegetative form. In some embodiments, the food product includes both vegetative and spore forms of the bacteria. The compositions disclosed herein can be used in foods or beverages (e.g., health foods or beverages, foods or beverages for infants, foods or beverages for pregnant women, athletes, the elderly, or other specific populations, functional foods / beverages, foods or beverages for specified health uses, dietary supplements, foods or beverages for patients, or feed). Non-limiting examples of food and beverages include various beverages (e.g., juices, soft drinks, teas, drinks, jelly drinks and functional drinks), alcoholic beverages (e.g., beer), carbohydrate-containing foods (e.g., rice foods, noodles, bread and pasta), paste products (e.g., fish ham, sausage, seafood paste products), retort pouch products (e.g., curry, foods with thick starchy sauces, soups), dairy products (e.g., milk, milk drinks, ice cream, cheese and yogurt), fermented products (e.g., fermented miso, yogurt, fermented drinks and pickles), soy products, various confectionery products (e.g., Western confectionery products such as biscuits, cookies, etc.), Japanese confectionery products (including manju, anko, etc.), candy, chewing gum, gummy, ice desserts including jellies, cream caramels and frozen desserts, instant foods (e.g., instant soups and instant miso soups), microwave cooked foods, etc. Furthermore, these examples also include health foods and beverages prepared in the form of powders, granules, tablets, capsules, liquids, pastes and jellies.

[0287] Food products containing the bacterial strains described herein can be produced using methods known in the art and can contain the same amount of bacteria (e.g., weight, number, or CFU) as the pharmaceutical compositions provided herein. The appropriate selection of the amount of bacteria in the food product can depend on various factors, such as, for example, the serving size of the food product, the frequency of consumption of the food product, the particular bacterial strain contained in the food product, the amount of water in the food product, and / or additional conditions for the survival of the bacteria in the food product.

[0288] Examples of food products that can be formulated to contain any of the strains described herein include, but are not limited to, beverages, drinks, bars, snacks, dairy products, confectionery products, cereal products, ready-to-eat products, nutritional compositions (e.g., dietary supplements), and food or beverage additives.

[0289] In some embodiments, the subject has not received a dose of antibiotics prior to administration of the bacterial composition. In some embodiments, the subject has not received antibiotics at least 1, at least 2, at least 3, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 60, at least 90, at least 120, at least 180, or at least 360 days prior to administration of the compositions provided herein. In some embodiments, the person has not received antibiotics for the treatment of a pathogen infection. In some embodiments, the compositions provided herein include an initial treatment for a pathogen infection.

[0290] In some embodiments, the subject may be administered one or more doses of antibiotics prior to or in parallel with the bacterial composition. Generally, the first line of defense in treating pathogen infections is the administration of antibiotics. In some embodiments, the subject receives a single dose of antibiotics prior to the bacterial composition. In some embodiments, the subject receives multiple doses of antibiotics prior to the bacterial composition. In some embodiments, the subject receives at least 2, 3, 4, 5 or more doses of antibiotics prior to the bacterial composition. In some embodiments, the subject receives a dose of antibiotics substantially simultaneously with the bacterial composition. Examples of antibiotics that can be administered include, but are not limited to, kanamycin, gentamicin, colistin, metronidazole, vancomycin, clindamycin, fidaxomicin, and cefoperazone.

[0291] Table 1 below shows the SEQ ID NOs and associated strain IDs used in the compositions of the experiments disclosed herein. The closest bacterial species to the indicated strains are shown by genus-species. Also shown is the 16S rDNA sequence associated with each genus-species identified as the closest related genus-species. The percent alignment indicates the percent identity between the sequence of the indicated strain and the sequence from the closest genus-species. The alignment length is also shown. The GenBank accession numbers of the closest relatives are shown in the last column.

[0292] Table 1: Closest bacterial species to the strains described herein [Table 11-1] [Table 11-2] [Table 11-3] [Table 11-4]

[0293] Table 2: Bacterial species with high homology based on whole genome analysis [Table 12]

[0294] Table 3: Bacterial species with the highest degree of homology based on whole genome analysis [Table 13]

[0295] In some embodiments, in any of the compositions described herein, Clostridium bolteae can be replaced by Clostridium bolteae 90A9. In some embodiments, in any of the compositions described herein, Anaerotruncus colihominis can be replaced by Anaerotruncus colihominis DSM 17241. In some embodiments, in any of the compositions described herein, Eubacterium fissicatena can be replaced by Sellimonas instestinalis, Drancourtella massiliensis, or Drancourtella massiliensis GP1. In some embodiments, in any of the compositions described herein, Clostridium symbiosum can be replaced by Clostridium symbiosum WAL-14163. In some embodiments, in any of the compositions described herein, Blautia producta can be replaced by Clostridium bacterium CD5.1-1D4 or Blautia product ATCC27340. In some embodiments, in any of the compositions described herein, Dorea longicatena can be replaced by Dorea longicatena CAG:42. In some embodiments, in any of the compositions described herein, Clostridium innocuum can be replaced by Erysipelotrichaceae bacterium 21_3. In some embodiments, in any of the compositions described herein, Flavonifractor plautii can be replaced by Clostridium orbiscindens 1_3_50AFAA.

[0296] Aspects described herein provide pharmaceutical compositions comprising a purified bacterial mixture consisting of a strain comprising a 16S rDNA sequence having at least 95% homology to SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some aspects, the strain has at least 97% homology to SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some aspects, the strain has at least 98% homology to SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some aspects, the strain has at least 99% homology to SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21.

[0297] In some aspects, at least a portion of the bacteria in the pharmaceutical composition is in spore form. In some aspects, the pharmaceutical composition further comprises a pharma- cologically acceptable excipient.

[0298] In some aspects, the pharmaceutical composition is formulated for oral administration. In some aspects, the pharmaceutical composition is in the form of a capsule. In some aspects, the pharmaceutical composition is formulated for delivery to the colon. In some aspects, the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

[0299] Aspects described herein provide pharmaceutical compositions comprising a purified bacterial mixture consisting of a strain comprising a 16S rDNA sequence having at least 95% homology to SEQ ID NO: 124, SEQ ID NO: 129, SEQ ID NO: 132, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 146, SEQ ID NO: 152, and SEQ ID NO: 157. In some aspects, the strain has at least 97% homology to SEQ ID NO: 124, SEQ ID NO: 129, SEQ ID NO: 132, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 146, SEQ ID NO: 152, and SEQ ID NO: 157. In some aspects, the strain has at least 98% homology to SEQ ID NO: 124, SEQ ID NO: 129, SEQ ID NO: 132, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 146, SEQ ID NO: 152, and SEQ ID NO: 157. In some aspects, the strain has at least 99% homology to SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152 and SEQ ID NO:157.

[0300] In some aspects, at least some of the strains are in spore form.In some aspects, the pharmaceutical composition further comprises a pharma- cologically acceptable excipient.

[0301] In some aspects, the pharmaceutical composition is formulated for oral administration. In some aspects, the pharmaceutical composition is in the form of a capsule. In some aspects, the pharmaceutical composition is formulated for delivery to the colon. In some aspects, the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

[0302] Aspects described herein provide pharmaceutical compositions comprising a purified bacterial mixture comprising a strain comprising a 16S rDNA sequence having at least 95% homology to SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some aspects, the strain has at least 97% homology to SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some aspects, the strain has at least 98% homology to SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some aspects, the strain has at least 99% homology to SEQ ID NO:10, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21.

[0303] In some aspects, at least some of the strains are in spore form.In some aspects, the pharmaceutical composition further comprises a pharma- cologically acceptable excipient.

[0304] In some aspects, the pharmaceutical composition is formulated for oral administration. In some aspects, the pharmaceutical composition is in the form of a capsule. In some aspects, the pharmaceutical composition is formulated for delivery to the colon. In some aspects, the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

[0305] Aspects described herein provide pharmaceutical compositions comprising a purified bacterial mixture comprising a strain comprising a 16S rDNA sequence having at least 95% homology to SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157. In some aspects, the strain has at least 97% homology to SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157. In some aspects, the strain has at least 98% homology to SEQ ID NO:124, SEQ ID NO:129, SEQ ID NO:132, SEQ ID NO:137, SEQ ID NO:141, SEQ ID NO:146, SEQ ID NO:152, and SEQ ID NO:157. In some aspects, the strain has at least 99% homology to SEQ ID NO: 124, SEQ ID NO: 129, SEQ ID NO: 132, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 146, SEQ ID NO: 152, and SEQ ID NO: 157. In some aspects, at least some of the strains are in spore form. In some aspects, the pharmaceutical composition further comprises a pharma- cologically acceptable excipient.

[0306] In some aspects, the pharmaceutical composition is formulated for oral administration. In some aspects, the pharmaceutical composition is in the form of a capsule. In some aspects, the pharmaceutical composition is formulated for delivery to the colon. In some aspects, the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

[0307] Aspects described herein provide a pharmaceutical composition comprising a purified bacterial mixture consisting of the following strains: Clostridium bolteae, Anaerostruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea Longicatena, Erysipelotrichaceae bacterium, and Clostridium orbiscindens.

[0308] In some aspects, at least some of the strains are in spore form.In some aspects, the pharmaceutical composition further comprises a pharma- cologically acceptable excipient.

[0309] In some aspects, the pharmaceutical composition is formulated for oral administration. In some aspects, the pharmaceutical composition is in the form of a capsule. In some aspects, the pharmaceutical composition is formulated for delivery to the colon. In some aspects, the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

[0310] Aspects described herein provide a pharmaceutical composition comprising a purified bacterial mixture including the following strains: Clostridium bolteae, Anaerostruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea Longicatena, Erysipelotrichaceae bacterium, and Clostridium orbiscindens.

[0311] In some aspects, at least some of the strains are in spore form.In some aspects, the pharmaceutical composition further comprises a pharma- cologically acceptable excipient.

[0312] In some aspects, the pharmaceutical composition is formulated for oral administration. In some aspects, the pharmaceutical composition is in the form of a capsule. In some aspects, the pharmaceutical composition is formulated for delivery to the colon. In some aspects, the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

[0313] As an aspect described herein, there is provided a method of treating an infectious disease in a subject, the method comprising administering to the subject a pharmaceutical composition of any of the aspects described herein in an amount sufficient to treat the infectious disease. In some aspects, the infectious disease is a Clostridium difficile infection.

[0314] The nucleic acid sequences of 16S rDNA, or portions thereof, for the strains described herein are provided below:

[0315] [ka]

[0316] [ka]

[0317] [ka]

[0318] [ka]

[0319] [ka]

[0320] [ka]

[0321] [ka]

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[0376] The present invention is not limited in its application to the details of the construction and organization of components set forth in the following description or illustrated in the drawings. The present invention can be implemented or carried out in other embodiments and in various ways. Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. In this specification, the words "comprise," "include," "have," "contain," "involve," and variations thereof are meant to encompass the items listed thereafter and equivalents thereof, as well as additional items.

[0377] Unless otherwise defined herein, scientific and technical terms used in connection with this disclosure have the meanings commonly understood by those skilled in the art. Furthermore, unless otherwise required by context, singular terms include the plural, and plural terms include the singular. The methods and techniques of this disclosure are generally carried out according to conventional methods well known in the art. The nomenclature used in connection with, and techniques of, biochemistry, enzymology, molecular cell biology, microbiology, virology, cell or tissue culture, genetics, and protein and nucleic acid chemistry described herein are generally well known and commonly used in the art. The methods and techniques of this disclosure are generally carried out according to conventional methods well known in the art, and conventional methods described in various general and more specific references cited and described throughout this specification, unless otherwise indicated.

[0378] The present invention is further illustrated by the following examples, which should not be construed as further limiting in any way. The entire contents of the references cited throughout this application (including literature references, issued patents, published patent applications, and co-pending patent applications) are hereby specifically incorporated by reference, particularly for the teachings referenced herein above. However, the citation of any reference is not intended as an admission that the reference is prior art. EXAMPLES

[0379] Example 1: Mouse model of C. difficile infection Mouse husbandry Experiments were performed with C57BL / 6J female mice purchased from Jackson Laboratories (Bar Harbor, ME) and housed in ventilated, sterile cages. All animals were maintained in an SPF facility. Animals were acclimated in the animal facility for at least 3 days prior to testing (i.e., initiation of antibiotic test course). For experiments involving C. difficile infection, 10–10 4 Mice were gavaged with spores of C. difficile VPI 10463. Experiments were performed in accordance with institutional guidelines and with the approval of the Institutional Animal Care and Use Committee. Animals were provided with sterile food and drinking water.

[0380] Preparation of live biotherapeutics (LBP) Each strain was isolated from fecal material obtained from a healthy donor. Individual strains were streaked from 15 percent glycerol frozen stocks onto Eggerth Gagnon (EG) agar plates containing 5% horse blood in an anaerobic chamber and incubated at 37°C for 24-48 hours. Colonies were inoculated into pre-reduced liquid peptone yeast glucose (PYG) medium and grown to density (static in an anaerobic chamber) for 24-48 hours. The optical density (OD 600 ) and prepare live biotherapeutic product (LBP) cocktails in an anaerobic chamber at OD 200 / mL for equal CFU ratio cocktails in PBS (sterile, pretreated). 600 The amount added was adjusted based on this.

[0381] Determination of C. difficile colony forming units (CFU) Fecal pellets were collected and transferred to an anaerobic chamber (<2 h) and homogenized in 500 μL of pre-reduced PBS by repeated pipetting with a pipette tip. Serial dilutions of fecal homogenates were prepared in pre-reduced PBS and 100 μL was spread onto cycloserine-cefoxitin-fructose agar (TCCFA) plates containing sodium taurocholate and incubated at 37°C under anaerobic conditions. CFU of C. difficile were enumerated at 48 h.

[0382] Susceptibility of mice to C. difficile infection Groups of mice were evaluated for susceptibility to C. difficile using three antibiotic regimens: (1) antibiotic cocktail, (2) clindamycin, or (3) cefoperazone (Figures 2 and 3). The antibiotic cocktail consisted of kanamycin (0.4 mg / ml), gentamicin (0.035 mg / ml), colistin (0.056 mg / ml), metronidazole (0.215 mg / ml), and vancomycin (0.045 mg / ml) in drinking water from day -10 to day -3, followed by a single intraperitoneal clindamycin injection (200 μg / mouse). Clindamycin administration was with a single intraperitoneal injection of clindamycin (200 μg / mouse) on day -1. Day designations are relative to day 0, the day of infection with C. difficile.

[0383] Mice were treated with the indicated antibiotic regimen and then administered 10 or 10 4 difficile spores (Figs. 2 and 3). An additional experimental arm was added to the antibiotic treatment model, where mice were treated with vancomycin after C. difficile infection (Fig. 4J, closed triangles).

[0384] Post-infection, mice were monitored daily for mortality / survival (Figures 4A-4D) and body weight (Figures 4E-4H), and fecal pellets were collected daily and used to enumerate C. difficile CFU, expressed as CFU / g feces (Figures 4I-4L).

[0385] Even after administration of 10 C. difficile spores, the group of mice receiving cefoperazone treatment showed significant weight changes (Figure 4H) and substantial C. difficile bacterial burden in fecal pellets (Figure 4L). These results indicated that the cefoperazone pretreatment regimen provides a good model for C. difficile infection and for evaluation of protection and / or treatment of C. difficile infection. In the absence of preinfection antibiotic treatment, C. difficile infection could not be established (Figure 4I) and all mice survived (Figure 4A) with no significant changes in weight (Figure 4E).

[0386] Example 2: Protection against C. difficile infection with a live biotherapeutic product (LBP) preparation

[0387] The following LBP compositions were evaluated for their ability to prevent and / or treat C. difficile infection. Composition A, Composition B, Composition C, Composition D, Composition E (e.g., Narushima et al., Gut Microbes (2014) 5(3) 333-339) and Composition I: A mixture of Clostridium scindens, Pseudoflavonifractor capillosus and Blautia hansenii (Figure 5).

[0388] Generally, the LBP cocktail was added to PYG medium and each mouse was gavaged with a dose in 250 μL of pre-reconstituted PBS (medium free). For composition E, bacteria were added at equal volume (not equal ratio / CFU) and administered in a 250 μL dose. Each LBP of compositions A-D contained 10 8 Contains a total of 10 CFU of each strain. 7 CFU of 10 8Composition I was administered at 10 CFU in a 250 μL dose. 6 The culture contained a total of 10,000 CFU of each of the three bacteria (approximately 333,000 of each of the three bacteria).

[0389] Groups of mice were treated with cefoperazone as described in Example 1 and then gavaged with the indicated compositions 2 days after the end of cefoperazone treatment. After 24 hours, mice were administered 10 4 Mice were infected with 1000 C. difficile spores (FIG. 5). Mice were also assessed for survival / mortality (FIG. 6), body weight (FIGS. 7A-7I) and CFU of C. difficile (FIGS. 8A-8C). The results indicate that administration of Composition B prior to C. difficile infection is an effective prevention and / or treatment against C. difficile infection.

[0390] Example 3: Protection and / or treatment against C. difficile infection with Composition B Groups of 10-12 week old mice were used in the C. difficile mouse model (Figure 9). The mice were treated with cefoperazone as described in Example 1. One group of mice was then treated with Composition B (10 per mouse) as described in Examples 1 and 2, two days after the end of the cefoperazone treatment. 8 CFU) were orally gavaged. The other group of mice did not receive any live biotherapeutic agent after cefoperazone treatment (control). After 24 hours, the mice were infected with C. difficile (10 4 C. difficile spores), followed by survival / mortality (Figure 10), body weight (Figure 11) and C. difficile load (CFU per gram of faeces, Figure 12). These results confirm the results of Example 2, demonstrating that treatment with Composition B prior to C. difficile infection is an effective prevention or treatment against C. difficile infection.

[0391] Example 4: Protection and / or treatment against C. difficile infection with LBP Composition F Figure 13 shows the strains of live biotherapeutic (LBP) Composition F. The genus-species classification indicates the closest species based on the sequence of the isolated strain. Figure 14 shows the classification of the strains in Composition F by the Clostridium cluster.

[0392] Groups of mice were administered cefoperazone as described in the examples above, followed by LBP or fecal transplants (FMT) from mice or humans (Figure 15). Composition B was administered at 10 4 Composition B was administered to the indicated groups on day -1; -2 and -1; or days -2, -1, 1, 2 and 3 based on infection with 10 C. difficile spores. Composition F was administered to the indicated groups on day -1, or days -2, -1, 1, 2 and 3 based on challenge with C. difficile spores. Additional groups underwent FMT (200 μL of 10 percent fecal sample per mouse) from mice or humans. Mice were then assessed for survival / mortality (FIG. 16), body weight (FIGS. 17A-17H), and C. difficile load (CFU / gram feces) (FIGS. 18A and 18B) on days 1, 3, 8 and 17 post-infection. These data demonstrate that Composition B, Composition F and FMT protect against and / or treat C. difficile infection.

[0393] Example 5: Protection and / or treatment against C. difficile infection with LBP compositions Figure 19 shows the strains of Composition G. The genus-species designation indicates the closest species based on the sequence of the isolated strain. Composition G includes a subset of the strains of Composition F. Groups of mice were administered cefoperazone as described in the examples above, followed by LBP. Composition B; Composition B-1 (Composition B plus Bacteroides); Composition B-2 (composition B excluding Flavonifractor plautii and adding Bacteroides); Composition F; Composition G; ethanol-treated human fecal samples; Composition B treated with ethanol; Frozen composition B; or Composition J: ethanol-treated Clostridium innocuum, Clostridium bolteae and Clostridium symbiosum; (See also Figure 20).

[0394] In compositions B-1 and B-2, Bacteroides ovatus (strain identifier 211-B; SEQ ID NO: 83) was used as the Bacteroides strain. Mice were inoculated with spores (10 4 ) and monitored daily (days 0-7 post-C. difficile infection) for survival / mortality (Figures 21 and 23) and body weight change (Figures 22A-22J and Figure 24). These data indicate that the composition protects against and / or treats C. difficile infection.

[0395] Example 6: Protection and / or treatment against C. difficile infection with LBP compositions Groups of mice were treated with cefoperazone as above and then administered human fecal transplant, Composition B, Composition B + 4 spores, or Composition H (Figure 25). "Composition B + 4 spores" refers to Composition B plus the following four strains in spore form: Clostridium bolteae, Anaerotruncus colihominis, Clostridium symbiosum, and Clostridium innocuum. Composition H contains the following six strains in spore form: Clostridium bolteae, Anaerotruncus colihominis, Clostridium symbiosum, Clostridium innocuum, Clostridium disporicum, and Erysipelatoclostridium ramosum (Figure 26).

[0396] For mice, then 10 4Mice were challenged with C. difficile VPI 10463 spores and monitored for survival / mortality (Figures 27A and 28A) and body weight (Figures 27B and 28B). Mice that lost more than 20% body weight relative to baseline were included in the mortality count in the survival curves. C. difficile burden was calculated by CFU in fecal pellets on days 1, 4, and 19 post-infection (Figures 29A-29C).

[0397] These data indicate that Composition B, as well as other compositions, can improve survival in a cefoperazone-induced C. difficile mouse model and may protect against and / or treat C. difficile infection.

[0398] Example 7: C. difficile toxin experiments Vero cells, epithelial cells derived from African green monkey kidney epithelium, are sensitive to a variety of bacterial toxins, including C. difficile B toxin. Exposure of cells to C. difficile B toxin inhibits the function of Rho, Rac and Cdc42, leading to a decrease in F-actin, changes in cell morphology (e.g., cell rounding) and ultimately apoptosis.

[0399] To determine whether administration of the bacterial compositions described herein affects the production or activity of B toxin of C. difficile, cellular assays were performed. Briefly, groups of mice were treated with cefoperazone as described above, administered human fecal transplant (FMT) ("4-3"), Composition B ("5-3"), Composition B plus four spore-form strains: Clostridium bolteae, Anaerotruncus colihominis, Clostridium symbiosum, and Clostridium innocuum ("7-4"), or were untreated. Each group of mice was then administered 10 4Mice were infected with C. difficile using 100 mg of C. difficile spores. Groups of mice that received no treatment after administration of cefoperazone and before C. difficile infection are designated "2-1 (Cdiff)" and "2-4 (Cdiff)." An additional group of mice, designated "N3 (healthy)," was not exposed to C. difficile.

[0400] Fecal pellets were collected from each group of mice, weighed, homogenized in PBS, and normalized to a constant concentration (approximately 25 mg / mL). Samples were centrifuged to prepare clear sample supernatants, which were then diluted in 10-fold serial dilutions, from 1:10 of the clear pellet supernatant to 1:10 of the clarified pellet supernatant. -6 Dilutions ranging from 0.1 to 0.2 mg / mL were prepared. Cultured Vero cells were exposed to the diluted samples for approximately 18 hours and then observed by phase contrast microscopy to assess morphological changes associated with exposure to C. difficile toxins (i.e., cell rounding). Cells were scored based on the highest concentration of supernatant that showed no morphological changes (Figure 30). Samples from mice treated with Composition B prior to C. difficile infection had reduced amounts of C. difficile B toxin compared to samples from control mice that received no treatment after cefoperazone administration and prior to C. difficile infection ("2-1(Cdiff)" and "2-4(Cdiff)"), as well as compared to samples from mice that underwent FMT. Notably, samples from mice treated with Composition B had reduced amounts of C. difficile B toxin compared to samples from mice treated with Composition B with additional spores.

[0401] Example 8: In vitro competition between Composition B and C. difficile The ability of Composition B to inhibit Clostridium difficile growth in an in vitro mixed culture competition assay was assessed. Individual strains of Composition B, C. difficile (Cdiff), Clostridium bifermentans, and Bacteroides thetaiotaomicron, from glycerol frozen stocks, were streaked onto Eggerth-Gagnon agar plates containing horse blood (EG+HB). Single colonies of each strain were then inoculated into Brain Heart Infusion (BHI) liquid medium and grown in axenic culture for 24-48 hours.

[0402] The semi-turbid cultures were subcultured, then grown to logarithmic phase, and finally diluted and combined to an optical density (OD) of 0.1. 600 ) were prepared. Logarithmic-phase Cdiff cultures were added to the mixed cultures at a final concentration of OD 0.1. Cultures were combined and incubated for 2–3 h, after which samples were collected, serially diluted, and plated on taurocholate-cycloserine-cefoxitin-fructose agar (TCCFA) plates to select for Cdiff growth. After 48–72 h, colony-forming units (CFU) of Cdiff were determined for each competition experiment by manual colony counting.

[0403] EG+HB agar plates were prepared according to standard procedures and reduced in an anaerobic environment for at least 6–8 h before use. Liquid BHI medium was purchased from BD Biosciences (catalog #211059, San Jose, CA), prepared according to the manufacturer's instructions, and reduced in an anaerobic environment for at least 18–24 h before use. TCCFA plates were prepared according to standard procedures and reduced in an anaerobic environment for at least 6–8 h before use. Clostridium difficile strains used in the experiments: American Type Culture Collection (ATCC) 43255.

[0404] Table 4: Composition B strain [Table 14]

[0405] Strains were streaked from glycerol frozen stocks onto EG+HB agar plates and grown inside an anaerobic chamber for 48-72 hours. A single colony was inoculated into 10 mL of BHI medium and grown in an anaerobic chamber at 37°C for 24-48 hours. The semi-turbid culture was then diluted to an OD of 0.1 and grown in an anaerobic chamber at 37°C for 2-3 hours.

[0406] Exponentially growing cultures were diluted and combined at equal OD. In the competition assay, OD 600 Each strain in Composition B (Table 4) was combined in equal portions based on the final consortium OD of 0.1. 600 C. bifermentans and B. thetaiotaomicron were prepared and competed with Cdiff individually at OD 0.1. The OD600 of Cdiff for each mixed culture competition experiment was 0.1. After combination, the cultures were incubated in an anaerobic chamber at 37°C for 2-3 hours and then prepared for enumeration on Cdiff selection plates.

[0407] TCCFA plates are selective for Cdiff growth; neither strains from Composition B nor any of the control strains (C. bifermentans and B. thetaiotaomicron) grow on these plates. A 100 μL sample of each competing culture was withdrawn in the anaerobic chamber and serially diluted 1:10 to a final concentration of 1 × 10 -6 The antibody was diluted to 1 × 10 -4 ~1×10 -6 CFU count plates were prepared by spreading 100 μL of each dilution onto TCCFA plates using a sterile spreading loop. CFU plates were incubated in an anaerobic chamber at 37°C for 48-72 hours. CFU counts were performed by manual counting of colonies.

[0408] To determine the effect of competition, the CFU ratios determined for the competition samples versus Cdiff alone were calculated and expressed as a percentage. Inhibition of Cdiff growth by Composition B cocktail was compared to the response of B. thetaiotaomicron (negative control) and C. bifermentans (positive control). The results are shown in Table 5 and Figure 31.

[0409] Table 5: Summary of in vitro competition results. [Table 15]

[0410] Data are expressed as Cdiff CFU as a percentage of control. Each n represents a single biological replicate, independent of other measurements.

[0411] In in vitro competition, Composition B inhibited Cdiff growth by 15.1±16.2% versus control (no competitor strain(s)). This result is consistent with the inhibition observed with the positive control C. bifermentans, which was 11.7±16.5% versus control. The negative control B. thetaiotaomicron showed a negligible effect on Cdiff growth, at 65.6±43.8% versus control. Given the inherent variability in CFU assessment, <25% growth inhibition versus control is considered significant inhibition, and the positive control and Composition B cocktails met this threshold of activity. The Composition B consortium showed Cdiff growth attenuation in vitro equivalent to that observed with direct competition with C. bifermentans. Direct competition with B. thetaiotaomicron did not significantly inhibit Cdiff growth.

[0412] Example 9: Determination of in vitro short chain fatty acid production Each strain in Composition B was evaluated for individual short chain fatty acid (SCFA) production in vitro. Composition B strains were grown in pure culture in an anaerobic chamber. Spent supernatants after incubation in liquid medium were collected by centrifugation, filter sterilized, and then stored at <-70°C. Frozen clarified supernatant samples were analyzed for short chain fatty acids (SCFA).

[0413] EG+HB agar plates (Eggerth-Gagnon agar plates with horse blood) were prepared according to standard procedures and reduced in an anaerobic environment for at least 6–8 h before use. Liquid PYG medium (prepared, reduced) was purchased from Anaerobe Systems (catalog #AS-822, Morgan Hill, CA).

[0414] Strains were streaked onto EG+HB agar plates from 15% glycerol frozen stocks and grown in an anaerobic chamber for 48–72 h. A single colony was inoculated into 7 mL of PYG medium and grown in an anaerobic chamber at 37°C for 24–48 h. Samples were harvested for CFU enumeration and filtration when the optical density (OD) was ≥ 0.2, unless otherwise stated. In an anaerobic chamber, 100 μL of semi-turbid culture sample was harvested and serially diluted 1:10 to a final concentration of 1 × 10 -6 Diluted to 1 × 10 -4 ~1×10 -6For dilutions of , CFU counting plates were prepared by spreading 100 μL of dilution onto EG+HB agar plates using sterile glass beads. CFU plates were incubated in an anaerobic chamber for 48–72 h. CFU counting was performed using EasyCount 2 (bioMerieux SA, Marcy-l'Etoile, France). Immediately after the semi-turbid culture samples were harvested for CFU counting, the remaining semi-turbid culture was centrifuged at approximately 1000 RCF for 10 min until a pellet of cellular debris was produced. The clear supernatant was transferred to a 0.2 μm plate filter and vacuum filtered to remove any remaining particulates prior to bioanalysis. In case of clogging of the filter plate, the clear supernatant was manually filtered using a 0.2 μm syringe filter. Aliquots of the filtered supernatant were prepared and stored at <-70 °C prior to bioanalysis for SCFAs.

[0415] To facilitate comparison between samples, raw SCFA data (μg / mL) were expressed as the log of CFU measured / estimated for each corresponding culture. 10 The results are shown in Tables 6 and 7 below.

[0416] Table 6: CFU counts for Composition B strains [Table 16]

[0417] Table 7: SFCA produced by individual composition B strains [Table 17]

[0418] Seven strains in Composition B were found to produce significant amounts (>1 μg / Log(CFU / mL)*mL) of a two-carbon SCFA (acetate). One strain (#211) produced substantial amounts of a three-carbon SCFA (propionate). Four strains in Composition B produced substantial amounts of a four-carbon SCFA (butyrate). Trace amounts of other SCFAs (<1 μg / Log(CFU / mL)*mL) were also produced by strains in Composition B.

[0419] Example 10: Induction of regulatory T cells (Treg) by Composition B Each of the strains in Composition B was grown to logarithmic phase and combined to give approximately 10 8 The total dose of cfu was determined. Germ-free mice were inoculated by oral gavage with Composition B or a negative control and sacrificed after 4 weeks of colony formation. Lamina propria leukocytes were isolated from colonic tissue of individual mice by standard procedures and counted by flow cytometry. Regulatory T cell content was assessed as the percentage of Foxp3 positive cells among CD4+ T cells.

[0420] As shown in FIG. 32, mice vaccinated with Composition B were found to have significantly more regulatory T cells compared to control vaccinated mice.

Claims

1. (i) a strain belonging to the species Flavonifractor plautii; (ii) Strains belonging to the species Anaerotruncus colihominis; (iii) a strain belonging to the species Sellimonas intestinalis; (vi) strains belonging to the species Clostridium symbiosum; (V) a strain belonging to the species Clostridium bolteae; (vi) Strains belonging to the species Dorea longicatena; (vii) a strain belonging to the species Blautia producta; and (viii) Strains belonging to the species Clostridium innocuum wherein the medicament comprises two or more dosage forms, each dosage form comprising at least one of said strains.

2. (i) a strain belonging to the species Flavonifractor plautii; (ii) a strain belonging to the species Anaerotruncus colihominis; (iii) a strain belonging to the species Drancourtella massiliensis; (vi) strains belonging to the species Clostridium symbiosum; (V) a strain belonging to the species Clostridium bolteae; (vi) Strains belonging to the species Dorea longicatena; (vii) a strain belonging to the species Blautia producta; and (viii) strains belonging to the species Clostridium innocuum wherein the medicament comprises two or more dosage forms, each dosage form comprising at least one of said strains.

3. (i) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 124; (ii) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 129; (iii) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 132; (iv) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 137; (v) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 141; (vi) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 146; (vii) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 152; and (viii) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 157; wherein the medicament comprises two or more dosage forms, each dosage form comprising at least one of said strains.

4. (i) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 124; (ii) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 129; (iii) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 132; (iv) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 137; (v) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 141; (vi) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 146; (vii) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 152; The medicament of claim 3, wherein the strain of (viii) comprises a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO:

157.

5. 5. A medicament according to any one of claims 1 to 4 for use in a method for treating or preventing Clostridium difficile in a subject, the method comprising administering to the subject two or more dosage forms.

6. 1. A medicament for use in a method for treating or preventing a Clostridium difficile infection in a subject, the medicament comprising: (i) a strain belonging to the species Flavonifractor plautii; (ii) a strain belonging to the species Anaerotruncus colihominis; (iii) a strain belonging to the species Sellimonas intestinalis; (vi) strains belonging to the species Clostridium symbiosum; (V) a strain belonging to the species Clostridium bolteae; (vi) Strains belonging to the species Dorea longicatena; (vii) a strain belonging to the species Blautia producta; and (viii) strains belonging to the species Clostridium innocuum wherein the strains (i) to (viii) are administered in more than one administration device.

7. 1. A medicament for use in a method for treating or preventing a Clostridium difficile infection in a subject, the medicament comprising: (i) a strain belonging to the species Flavonifractor plautii; (ii) a strain belonging to the species Anaerotruncus colihominis; (iii) a strain belonging to the species Drancourtella massiliensis; (vi) strains belonging to the species Clostridium symbiosum; (V) a strain belonging to the species Clostridium bolteae; (vi) Strains belonging to the species Dorea longicatena; (vii) a strain belonging to the species Blautia producta; and (viii) strains belonging to the species Clostridium innocuum wherein the strains (i) to (viii) are administered in more than one administration device.

8. 1. A medicament for use in a method for treating or preventing a Clostridium difficile infection in a subject, the medicament comprising: (i) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 124; (ii) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 129; (iii) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 132; (iv) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 137; (v) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 141; (vi) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 146; (vii) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 152; and (viii) a strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 157; wherein the strains (i) to (viii) are administered in more than one administration device.

9. (i) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 124; (ii) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 129; (iii) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 132; (iv) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 137; (v) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 141; (vi) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 146; (vii) The strain comprises a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 152; The medicament described in claim 8, wherein the strain of (viii) comprises a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO:

157.

10. The pharmaceutical composition according to any one of claims 5 to 9, wherein the method is for preventing Clostridium difficile infection in a subject.

11. The pharmaceutical composition of claim 10, wherein the method is for preventing recurrence of Clostridium difficile infection in a subject.

12. The method of any one of claims 1 to 11, wherein the strain is present in two or more pharmaceutical compositions, each pharmaceutical composition comprising a pharmacologically acceptable excipient.

13. The method of claim 12, wherein each pharmaceutical composition is formulated for delivery to the small intestine.

14. 14. The method of claim 12 or 13, wherein each pharmaceutical composition is formulated for delivery to the colon.

15. The method of any one of claims 12 to 14, wherein each pharmaceutical composition comprises a pH-sensitive composition comprising one or more enteric polymers.

16. The pharmaceutical composition according to any one of claims 12 to 15, wherein each pharmaceutical composition comprises a hydrogel.

17. The pharmaceutical of claim 16 , wherein the hydrogel comprises a cellulosic polymer.

18. The pharmaceutical composition according to any one of claims 12 to 17, wherein the subject is administered an antibiotic prior to administration of the pharmaceutical composition.

19. 19. The pharmaceutical of claim 18, wherein the antibiotic is vancomycin, kanamycin, gentamicin, colistin, metronidazole, clindamycin, fidaxomicin or cefoperazone.

20. The pharmaceutical composition according to claim 19, wherein the antibiotic is vancomycin.