Compositions and methods for controlling pathogenic organisms

Abstract

Provided herein are compositions and methods for inhibiting infection by pathogenic organisms. Also provided herein are compositions and methods for reducing or preventing colonization by pathogenic organisms, and methods for treating infection by pathogenic organisms. Also provided herein are compositions comprising taurine, and methods of using such compositions for inhibiting infection by pathogenic organisms, preventing colonization by pathogenic organisms, and methods for treating infectious pathogenic organisms.

Description

[Technical Field]

[0001] Related Applications This application claims the benefit under 35 USC § 119(e) of U.S. Provisional Patent Application No. 63 / 151,003, filed February 18, 2021, the entire contents of which are incorporated herein by reference.

[0002] Reference to a sequence listing submitted as a text file via EFS-WEB This application contains a Sequence Listing that was submitted in ASCII format via EFS-Web and is incorporated herein by reference in its entirety. The ASCII copy, created on February 17, 2022, is named P074570026WO00-SEQ-NTJ.txt and is 157,149 bytes in size. [Background technology]

[0003] background Multidrug-resistant organisms (MDROs; "superbugs"), microorganisms that have developed resistance to one or more classes of antimicrobial agents, such as antibiotics, have emerged as a serious global health threat. It is estimated that more than 2 million people in the United States suffer from serious bacterial infections resistant to one or more antibiotics each year (CDC, Antibiotic Resistance Threats in the United States, 2013, Publication No. CS239559-B). Treatment options for individuals with MDROs are extremely limited, making prevention of transmission crucial. The most important factors contributing to the creation and proliferation of MDROs are the use and overuse / misuse of antibiotics, and the problem is expected to increase in severity as additional pathogenic organisms with antibiotic resistance emerge (CDC, 2013; WHO 2017). Summary of the Invention

[0004] overview In some embodiments, the present disclosure provides: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaThe present invention provides a composition comprising two or more purified bacterial strains of a species selected from the group consisting of purified bacterial strains of Akkermansia wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.

[0005] In some aspects, the disclosure provides a composition comprising two or more purified bacterial strains, wherein the two or more purified bacterial strains comprise a 16S rDNA sequence having at least 97% sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-47.

[0006] 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, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, or at least 47 purified bacterial strains.

[0007] In some aspects, the disclosure provides compositions comprising purified bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae. In some aspects, the disclosure provides compositions comprising purified bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36.

[0008] In some embodiments of the compositions provided herein, the compositions comprise bacterial strains derived from two or more human donors. In some embodiments, any of the compositions described herein may further comprise taurine.

[0009] In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes or Bacteroidetes; one or more purified bacterial strains selected from the group consisting of Escherichia species and Fusobacterium species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes; one or more purified bacterial strains of Escherichia species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes; one or more purified bacterial strains of Fusobacterium species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Bacteroidetes; one or more purified bacterial strains of Escherichia species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Bacteroidetes; one or more purified bacterial strains of Fusobacterium species; and taurine.

[0010] In some aspects, the present disclosure provides purified bacterial strains belonging to the Escherichia species, purified bacterial strains belonging to the Fusobacterium species, as well as Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium The present invention provides a composition comprising one or more purified bacterial strains of a species selected from the group consisting of: faecis; and taurine.

[0011] In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species, and one or more purified bacterial strains of a species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, and Phascolarctobacterium faecium; and taurine.

[0012] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the Escherichia species and one or more purified bacterial strains of a species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.

[0013] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the Fusobacterium species and one or more purified bacterial strains of a species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faeces; and taurine.

[0014] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species, and one or more purified bacterial strains of a species selected from the group consisting of Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteriodes cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.

[0015] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the species Escherichia and one or more purified bacterial strains of a species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteriodes cellulosilyticus, Bacteroides faeces, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.

[0016] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the species Fusobacterium and one or more purified bacterial strains of a species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteriodes cellulosilyticus, Bacteroides faeces, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.

[0017] In some aspects, the disclosure provides a composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species; and taurine.

[0018] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, Escherichia; and taurine.

[0019] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, Fusobacterium; and taurine.

[0020] In some aspects, the disclosure provides a composition comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species; and taurine.

[0021] In some aspects, the present disclosure provides a composition comprising a purified bacterial strain belonging to the species Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, Escherichia; and taurine.

[0022] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, Fusobacterium; and taurine.

[0023] In some cases, Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613)、cf.Clostridium sp.MLG055(Erysipelotrichaceae bacterium 2_2_44A)、Clostridium indolis(Anaerostipes caccae DSM 14662)、Anaerotruncus colihominis(Anaerotruncus colihominis DSM 17241)、Ruminococcus sp.ID8(Lachnospiraceae bacterium 2_1_46FAA)、Clostridium lavalense(Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp.D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp.The present invention provides a composition comprising a purified bacterial strain belonging to the species Escherichia 316002 / 08 (Clostriales bacterium 1_7_47FAA), a purified bacterial strain belonging to the species Fusobacterium 3_1_57FAA_CT1, a purified bacterial strain belonging to the species Escherichia 316002 / 08 (Clostriales bacterium 1_7_47FAA), a purified bacterial strain belonging to the species Fusobacterium ...

[0024] In some cases, Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613)、cf.Clostridium sp.MLG055(Erysipelotrichaceae bacterium 2_2_44A)、Clostridium indolis(Anaerostipes caccae DSM 14662)、Anaerotruncus colihominis(Anaerotruncus colihominis DSM 17241)、Ruminococcus sp.ID8(Lachnospiraceae bacterium 2_1_46FAA)、Clostridium lavalense(Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp.D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp.The present invention provides a composition comprising purified bacterial strains belonging to the Escherichia species, such as Clostriales bacterium 1_7_47FAA, Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), and Escherichia sp.; and taurine.

[0025] In some cases, Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613)、cf.Clostridium sp.MLG055(Erysipelotrichaceae bacterium 2_2_44A)、Clostridium indolis(Anaerostipes caccae DSM 14662)、Anaerotruncus colihominis(Anaerotruncus colihominis DSM 17241)、Ruminococcus sp.ID8(Lachnospiraceae bacterium 2_1_46FAA)、Clostridium lavalense(Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp.D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp.The present invention provides a composition comprising purified bacterial strains belonging to the species Fusobacterium 316002 / 08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), and Fusobacterium; and taurine.

[0026] In some aspects, the disclosure provides a composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to the species Escherichia, a purified bacterial strain belonging to the species Fusobacterium; and taurine.

[0027] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, Escherichia; and taurine.

[0028] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, Fusobacterium; and taurine.

[0029] In some aspects, the present disclosure relates to Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comest, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faeci, a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species; and taurine.

[0030] In some aspects, the present disclosure relates to Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteriodes cellulosilyticus, Bacteroides uniformis, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Alistipes shahii, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecis, a purified bacterial strain belonging to the species Escherichia, a purified bacterial strain belonging to the species Fusobacterium; and taurine.

[0031] In some aspects, the disclosure provides a composition comprising Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteriodes cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Alistipes putredinis, Alistipes shahii, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, a purified bacterial strain belonging to the species Escherichia, a purified bacterial strain belonging to the species Fusobacterium; and taurine.

[0032] In some embodiments, the present disclosure provides a composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.

[0033] In some embodiments, the present disclosure provides a composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Clostridium clostridioforme, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.

[0034] In some embodiments, the present disclosure provides a composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.

[0035] In some embodiments, the present disclosure provides a composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.

[0036] In some embodiments, the present disclosure provides a composition comprising Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.

[0037] In some embodiments, the present disclosure provides a composition comprising Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Clostridium citroniae, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Escherichia coli; and taurine.

[0038] In some embodiments, the present disclosure provides a composition comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.

[0039] In some embodiments, the present disclosure provides a composition comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Fusobacterium mortiferum, Escherichia coli; and taurine.

[0040] In some embodiments, the present disclosure provides a composition comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.

[0041] In some aspects, the disclosure provides a composition comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.

[0042] In some aspects, the disclosure provides compositions comprising one or more purified bacterial strains of the species Bacteroides vulgatus, Clostridium citroniae, and Phascolarctobacterium faecium, and a species selected from the group consisting of Bacteroides faecis, Bacteroides ovatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Agathobaculum butyriciproducens, Fusobacterium mortiferum, and Escherichia coli; and taurine.

[0043] In some aspects, the disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides faecis, Bacteroides vulgatus, Odoribacter splanchnicus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.

[0044] In some aspects, the disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.

[0045] In some aspects, the disclosure provides a composition comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.

[0046] In some aspects, the disclosure provides compositions comprising a purified bacterial strain of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae; and taurine. In some aspects, the disclosure provides compositions comprising a purified bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36; and taurine.

[0047] In some embodiments, any of the compositions described herein may further comprise one or more strains selected from the group consisting of Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.

[0048] In some embodiments, the composition further comprises taurine. In some embodiments, the composition comprises about 40 mg to about 3000 mg of taurine. In some embodiments, the composition comprises about 100 mg to about 2000 mg of taurine. In some embodiments, the composition comprises about 500 mg to about 1500 mg of taurine.

[0049] In some embodiments, the composition is effective in inhibiting the replication, survival, and / or colonization of one or more pathogenic organisms. In some embodiments, the composition is effective in treating an infection by a pathogenic organism in a subject. In some embodiments, the pathogenic organism is susceptible to an antibiotic. In some embodiments, the pathogenic organism is resistant to one or more antibiotics. In some embodiments, the pathogenic organism is a multidrug-resistant organism.

[0050] In some embodiments, the multidrug-resistant organism is carbapenem-resistant Enterobacteriaceae (CRE) or extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. In some embodiments, the carbapenem-resistant Enterobacteriaceae (CRE) is carbapenem-resistant Klebsiella pneumoniae. In some embodiments, the carbapenem-resistant Klebsiella pneumoniae is carbapenem-resistant Klebsiella pneumoniae ATCC 700721. In some embodiments, the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae or EBSL-producing E. coli. In some embodiments, the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae subsp. pneumoniae (ATCC 700721), ESBL-producing E. coli ATCC BAA 2777, adherent / invasive E. coli (AIEC), Shiga toxin-producing E. coli (STEC), Verocytotoxin-producing E. coli (VTEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), or diffusely adherent E. coli (DAEC).

[0051] In some embodiments, the bacterial strains are freeze-dried. In some embodiments, the bacterial strains are spray-dried. In some embodiments, one or more of the bacterial strains are in spore form. In some embodiments, each bacterial strain is in spore form. In some embodiments, one or more of the bacterial strains are in vegetative form. In some embodiments, each of the bacterial strains is in vegetative form. In some embodiments, the composition further comprises one or more enteric polymers.

[0052] In some embodiments, the pharmaceutical composition comprises 1 x 10 per bacterial strain. 6 ~1×10 10In some embodiments, each bacterial strain is present in the composition in the same CFU amount (e.g., 1 x 10 8 present in CFU).

[0053] In some aspects, the present disclosure provides a pharmaceutical composition comprising any of the compositions described herein and a pharmaceutically acceptable excipient.

[0054] In some embodiments, the pharmaceutical composition is formulated for oral delivery. In some embodiments, the pharmaceutical composition is formulated for intestinal delivery. In some embodiments, the pharmaceutical composition is formulated for colonic delivery. In some embodiments, the pharmaceutical composition is administered as a single dose. In some embodiments, the pharmaceutical composition is administered as multiple doses. In some embodiments, each dose comprises the administration of multiple capsules.

[0055] In some aspects, the present disclosure provides a food product comprising any of the compositions comprising the bacterial strains provided herein and nutrients.

[0056] In some aspects, the present disclosure provides methods for inhibiting infection by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of any of the bacterial strains, pharmaceutical compositions, or food-containing compositions described herein.

[0057] In some aspects, the present disclosure provides methods of reducing or preventing colonization by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of any of the bacterial strains, pharmaceutical compositions, or food-containing compositions described herein.

[0058] In some aspects, the present disclosure provides methods of treating an infection by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of any of the bacterial strains, pharmaceutical compositions, or food-containing compositions described herein.

[0059] In some embodiments of the methods provided herein, the pathogenic organism is a multidrug-resistant organism. In some embodiments, the pathogenic organism is Klebsiella pneumoniae. In some embodiments, the Klebsiella pneumoniae is multidrug-resistant. In some embodiments, the multidrug-resistant Klebsiella pneumoniae is carbapenem-resistant Klebsiella pneumoniae.

[0060] In some embodiments, the pathogenic organism is an extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. In some embodiments, the ESBL-producing Enterobacteriaceae is Escherichia coli (E. coli). In some embodiments, the E. coli is adherent / invasive E. coli (AIEC), Shiga toxin-producing E. coli (STEC), Verocytotoxin-producing E. coli (VTEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), or diffusely adherent E. coli (DAEC).

[0061] In some embodiments, the subject is a human. In some embodiments, the composition is administered to the subject by oral administration. In some embodiments, the composition is administered to the subject by rectal administration. In some embodiments, the administering inhibits replication, survival, and / or colonization of a pathogenic organism. In some embodiments, administration of the composition is not preceded by administration of vancomycin. In some embodiments, the administration further comprises administering an antibiotic to the subject prior to administration of the composition. In some embodiments, the antibiotic is vancomycin.

[0062] In some embodiments, the method further includes administering to the subject a composition comprising taurine. In some embodiments, the composition comprising taurine is administered to the subject before or after administration of any of the compositions or foods described herein containing the purified bacterial mixture. In some embodiments, the subject is administered about 40 mg to about 3000 mg of taurine per day. In some embodiments, the subject is administered about 100 mg to about 2000 mg of taurine per day. In some embodiments, the subject is administered about 500 mg to about 1500 mg of taurine per day. [Brief explanation of the drawings]

[0063] The accompanying drawings are not drawn to scale. The drawings are merely illustrative and are not necessary to enable the present disclosure. For clarity, not every component may be labeled in every drawing. In the drawings: [Figure 1] FIG. 1 shows a timeline of an exemplary mouse model of carbapenem-resistant Enterobacteriaceae (“CRE”) or extended-spectrum β-lactamase-producing Enterobacteriaceae (“ESBL”) colonization experiments. [Figure 2] Figure 2 shows extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae colonization (colony-forming units, "CFU") levels in mice 14 days after treatment ("D14 post-Tx"). From left to right, control (PBS), a composition of 36 bacterial strains ("36 mix"), or a stool fraction from a human donor (Donor 1 "SFL"). The dashed line represents the limit of detection. [Figure 3-1] FIG. 3 is a table showing the phylum, family, and species names of the bacterial strains present in a composition of 47 bacterial strains, referred to herein as the "47 mix." [Figure 3-2] FIG. 3 is a table showing the phylum, family, and species names of the bacterial strains present in a composition of 47 bacterial strains, referred to herein as the "47 mix." [Figure 4]Figure 4 shows carbapenem-resistant Klebsiella pneumoniae (CRE) or extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae colonization (colony-forming units, "CFU") levels in mice 14 days after treatment ("D14 post-Tx"). Mice were treated with control (PBS) or a composition of 47 bacterial strains. For each treatment, the data points in the left column represent CRE colonization, the data points in the right column represent ESBL colonization, and the LoD (dashed line) represents the limit of detection. [Figure 5A] Figures 5A and 5B show colonization of ESBL-producing Enterobacteriaceae and carbapenem-resistant Klebsiella pneumoniae (CRE) in mice treated with the indicated compositions. Figure 5A shows extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae colonization (colony-forming units, "CFU") levels in mice 7, 10, and 14 days after treatment ("days post-Tx"). [Figure 5B] Figures 5A and 5B show colonization of ESBL-producing Enterobacteriaceae and carbapenem-resistant Klebsiella pneumoniae (CRE) in mice treated with the indicated compositions. Figure 5B shows CRE colonization (colony-forming units, "CFU") levels in mice 7, 10, and 14 days after treatment ("days post-Tx"). For each time point, data are shown from left to right from mice treated with control (PBS), a 47-strain composition (47 Mix), a stool fraction from a second human donor (Donor 2 "SFL"), or a bacterial composition obtained by introducing stool from a first human donor into germ-free mice, obtaining stool from the mice, and preparing a fecal graft (Donor 1-inoculated mice FMT). The dashed line represents the limit of detection. DETAILED DESCRIPTION OF THE INVENTION

[0064] Detailed Description It can be difficult to suppress or prevent unwanted bacteria in a subject or bacterial colonization in a specific region of the body. Bacterial colonization can induce an immune response (local or systemic) in a subject, which can lead to serious illness. In particular, for multidrug-resistant organisms or organisms that have acquired antibiotic resistance, elimination with many conventional therapeutic agents, such as antibiotics, can be impossible due to resistance or tolerance to the therapeutic agent. Furthermore, it has recently been recognized that intestinal colonization by bacteria from the oral microbiota can affect the intestinal immune environment, such as by inducing a Th1-dominant immune response, leading to chronic inflammation and inflammatory conditions (see, e.g., Atarashi et al. Science (2017) 358 (359-365)). Normal bacterial colonization in different regions of the body, such as the oral cavity, can provide a reservoir of bacteria that can migrate and colonize other regions, such as the intestine.

[0065] The development of a live biological therapeutic product effective in promoting decolonization of the intestine against multiple pathogens (e.g., both carbapenem-resistant Enterobacteriaceae and extended-spectrum β-lactamase-producing Enterobacteriaceae) has been challenging. Provided herein are compositions and methods for reducing / inhibiting and / or preventing colonization by pathogenic organisms, such as multidrug-resistant organisms, e.g., carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Provided herein are compositions and methods for inhibiting infection by pathogenic organisms. Provided herein are compositions and methods for treating infection by pathogenic organisms. Also provided herein are compositions and methods for inducing regulatory T cell (Treg) production in response to pathogenic organisms. Provided herein are compositions and methods for inducing short-chain fatty acid (SCFA) production in response to pathogenic organisms. Also provided herein are compositions comprising a purified bacterial mixture and taurine, which may further assist in the colonization of the microbiome by beneficial bacterial strains and / or reducing colonization (resistance) to pathogens.

[0066] In some embodiments, one or more bacterial strains of the compositions provided herein colonize or recolonize the intestinal tract or a portion of the intestinal tract (e.g., the colon or cecum) of a subject. Such colonization or recolonization may also be referred to as grafting. In some embodiments, one or more bacterial strains of the compositions recolonize the intestinal tract (e.g., the colon or cecum) of a subject, for example, after another organism or population of organisms has been partially or completely removed (e.g., by antibiotic treatment). In some embodiments, one or more bacterial strains of the compositions recolonize the intestinal tract (e.g., the colon or cecum) after one or more pathogenic or other organisms (e.g., bacteria that induce an immune response) have been removed. In some embodiments, recolonization of the intestinal tract or a portion thereof by the bacterial strains of the compositions described herein prevents or inhibits colonization by undesirable organisms (e.g., pathogenic organisms, multidrug-resistant organisms, oral microbiota bacteria, bacteria that induce an immune response, pathogens, bacteria that reduce Treg production, bacteria that reduce SCFA production).

[0067] In some embodiments, one or more of the bacterial strains of the compositions can "outgrow" a pathogen or unwanted bacteria, such as a pathogenic organism, such as carbapenem-resistant Enterobacteriaceae (CRE) and / or extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Thus, in some embodiments, when a pathogen or unwanted bacteria (e.g., a pathogenic organism, a multidrug-resistant organism, e.g., carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae) and one or more bacteria of the compositions provided herein are both present in the intestinal tract (e.g., the colon or cecum), the one or more bacteria of the compositions provided herein outgrow (e.g., have a shorter doubling time) than the pathogen, thereby preventing the pathogen from accumulating in the intestinal tract (e.g., the colon or cecum). In some embodiments, the one or more bacteria of the compositions provided herein outgrow the pathogen in an otherwise intact or intact microbiota. In some embodiments, one or more bacteria of the compositions provided herein grow faster than pathogens in a depleted microbiota (e.g., after antibiotic treatment). In some embodiments, the faster growth occurs because one or more bacteria of the compositions provided herein are better at engrafting in the intestinal tract (e.g., the colon or cecum). In some embodiments, the faster growth occurs because one or more bacteria of the compositions provided herein are better at metabolizing nutrients present in the intestinal tract (e.g., the colon or cecum). In some embodiments, the bacterial strain compositions provided herein prevent or inhibit the replication of pathogens. In some embodiments, the bacterial strain compositions provided herein induce (kill) the death of pathogens. In some embodiments, the bacterial strains of the compositions provided herein can treat pathogenic infections due to synergistic effects between the bacterial strains.

[0068] In some embodiments, the bacterial compositions described herein prevent recolonization by pathogens or unwanted bacteria (e.g., pathogenic organisms, multidrug-resistant organisms, e.g., carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae). For example, in some embodiments, pathogens or unwanted bacteria have been reduced or eliminated from a subject using, e.g., a first therapeutic agent (such as an antibiotic), and the bacterial compositions described herein are administered to prevent recolonization of the subject. In some embodiments, the bacterial compositions described herein reduce or eliminate pathogens or unwanted bacteria from a subject and prevent recolonization of the subject.

[0069] In some embodiments, the bacterial strain combinations of the compositions provided herein are superior in nutrient utilization compared to pathogens or undesirable bacteria, thereby inhibiting the growth of pathogens or undesirable bacteria. In some embodiments, the bacterial strain combinations of the compositions provided herein are superior in grafting compared to pathogens or undesirable bacteria, thereby inhibiting the growth of pathogens or undesirable bacteria. In some embodiments, the bacterial strain combinations of the compositions provided herein are superior in nutrient utilization and grafting compared to pathogens or undesirable bacteria, thereby inhibiting the growth of pathogens or undesirable bacteria. In some embodiments, the bacterial strain combinations of the compositions provided herein inhibit the growth, survival, and / or colonization of pathogens or undesirable bacteria.

[0070] In some embodiments, the combination of bacterial strains of the compositions provided herein has antagonistic or inhibitory activity against pathogens or undesirable bacteria, thereby inhibiting the growth, survival, and / or colonization of the pathogens or undesirable bacteria. In some embodiments, at least one bacterial strain of the compositions provided herein has antagonistic or inhibitory activity against pathogens or undesirable bacteria, thereby inhibiting the growth, survival, and / or colonization of the pathogens or undesirable bacteria.

[0071] In some embodiments, the bacterial strains of the composition provide a synergistic effect in colonizing a specific niche in the intestinal tract (e.g., the colon or cecum). In some embodiments, the synergistic effect is provided by the ability of the combination to metabolize a specific nutrient. In some embodiments, the synergistic effect is provided by the ability of the combination to provide a specific metabolic product to the environment.

[0072] The bacterial strains used in the compositions provided herein are generally isolated from the microbiome of healthy individuals. In some embodiments, the compositions include strains derived from a single individual. In some embodiments, the compositions include strains derived from multiple individuals. In some embodiments, the bacterial strains are obtained, isolated, and grown individually from multiple individuals. The individually grown bacterial compositions may then be combined to provide the compositions of the present disclosure. It should be understood that the origin of the bacterial strains in the compositions provided herein is not limited to the human microbiome from a healthy individual. In some embodiments, the bacterial strains are derived from a human with a dysbiotic microbiome. In some embodiments, the bacterial strains are derived from a non-human animal or the environment (e.g., soil or surface water). In some embodiments, the combinations of bacterial strains provided herein are derived from multiple sources (e.g., a human and a non-human animal).

[0073] 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.

[0074] Generally, bacterial strains can be phylogenetically classified with other closely related strains and species based on their 16S rRNA (or 16S rDNA) nucleic acid sequences. Methods for determining the identity of a particular bacterial species based on 16S rRNA (or 16S rDNA) nucleic acid sequences are well known in the art (see, for example, Jumpstart Consortium Human Microbiome Project Data Generation Working, G. PLoS One (2012) 7, e39315).

[0075] It should be understood that any of the compositions described herein may contain multiple strains of a particular bacterial species. For example, in some embodiments, a composition may include two strains of the species Absiella innocuum.

[0076] The present disclosure includes Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Clostridium bifermentans, Paeniclostridium sordellii, Clostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium citroniae, Clostridium_M clostridioforme, Clostridium clostridioforme, Eubacterium_E hallii, Eubacterium hallii, Agathobacer rectale, Eubacterium rectale, Blautia producta, Blautia_A obeum, Blautia obeum Dorea longicatena, Coprococcus_B comes, Coprococcus comes, Anaerostipes caccae, Agathobaculum sp, AgathobaculumThe present invention encompasses compositions comprising bacterial strains that share close sequence identity or homology with and / or fall within the species of Acinetobacter pylori, Acinetobacter cystis ...

[0077] In some embodiments, the compositions disclosed herein comprise two or more bacterial strains. In 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, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47 or more bacterial strains (e.g., purified bacterial strains).

[0078] It should be understood that the terms "bacteria" and "bacterial strain" as used herein are interchangeable. Compositions described herein containing multiple purified bacterial strains may also be referred to as "live bacterial products."

[0079] In one aspect, the present disclosure provides a live bacterial product called the "47 mix" (see Figures 3-5). As shown in Figure 3 and Table 1, the composition called 47 mix contains the following species: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, RuminococcusIn some embodiments, the composition further comprises taurine.

[0080] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises two or more (e.g., 2, 3, 4, 5, or more) purified bacterial strains of a species selected from the group consisting of: Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.

[0081] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaThe bacterial strains comprise two or more (e.g., 2, 3, 4, 5, or more) bacterial strains of species selected from the group consisting of A. wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.

[0082] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises taurine.

[0083] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises bacterial strains of the species: Akkermansia wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.

[0084] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises a bacterial strain of the species: Akkermansia wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.

[0085] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition consists essentially of bacterial strains of the species: A. wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine. In some embodiments, "consisting essentially of," as used herein, refers to a composition that does not include additional therapeutically active bacterial strains.

[0086] It has a range of 38 sq. ft. and 38 sq. ft. With a slightly larger range of snowflakes, Collinsella aerofaciens、Bifidobacterium longum、Bifidobacterium pseudocatenulatum、Bifidobacterium adolescentis、Bacteroides caccae、Bacteroides xylanisolvens、Bacteroides cellulosilyticus、Bacteroides uniformis、Bacteroides_B vulgatus、Bacteroides fragilis、Bacteroides thetaiotaomicron、Bacteroides faecis、Bacteroides ovatus、Odoribacter splanchnicus、Parabacteroides distasonis、Parabacteroides merdae、Alistipes putredinis、Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectal.Blautia producta intestinhominis、Blautia luti、Blautia faecis、Blautia wexlerae、Ruminococcus faecis、ClostridiumIn some embodiments, the composition further comprises 38 bacterial strains of species selected from the group consisting of: Bacteroides diffusa, ...

[0087] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises taurine.

[0088] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises taurine.

[0089] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises 33 bacterial strains of species selected from the group consisting of: Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.

[0090] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises taurine.

[0091] In some embodiments, the composition comprises: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaIn some embodiments, the composition further comprises taurine.

[0092] In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes or Bacteroidetes; one or more purified bacterial strains selected from the group consisting of Escherichia species and Fusobacterium species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes; one or more purified bacterial strains of Escherichia species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes; one or more purified bacterial strains of Fusobacterium species; and taurine.

[0093] The phylum Firmicutes, also known as the phylum Bacillote, is a phylum of Gram-positive bacteria, many of which are spore-forming. Classes within the phylum Firmicutes include Clostridia, which are obligate anaerobes, and Bacilli, which can be obligate or facultative anaerobes. In some embodiments of a composition comprising a purified bacterial strain belonging to the phylum Firmicutes, the bacterial strain belongs to a class selected from the group consisting of Bacilli, Clostridia, and Negativicutes. In some embodiments, the composition comprises two or more bacterial strains belonging to the phylum Firmicutes, each of which independently belongs to a class selected from the group consisting of Bacilli, Clostridia, and Negativicutes.

[0094] Families within the phylum Firmicutes include Peptostreptococcaceae, Erysipelatotrichiaceae, Lachnospiraceae, Ruminococcaceae, Acidaminococcaceae, and Clostridiaceae. In some embodiments of a composition comprising a purified bacterial strain belonging to the phylum Firmicutes, the strain belongs to a family selected from the group consisting of Peptostreptococcaceae, Erysipelatotrichiaceae, Lachnospiraceae, Ruminococcaceae, Acidaminococcaceae, and Clostridiaceae. In some embodiments, the composition comprises two or more strains belonging to the phylum Firmicutes, wherein the two or more strains independently belong to a family independently selected from the group consisting of Peptostreptococcaceae, Erysipelatotrichiaceae, Lachnospiraceae, Ruminococcaceae, Acidaminococcaceae, and Clostridiaceae. In some embodiments, each of the strains belonging to the phylum Firmicultes independently belongs to a family selected from the group consisting of Peptostreptococcaceae, Erysipelatotrichiaceae, Lachnospiraceae, Ruminococcaceae, Acidaminococcaceae, and Clostridiaceae.

[0095] The phylum Bacteroidetes, also known as the phylum Bacteroidota, is a phylum of Gram-negative, non-spore-forming bacteria, which may be aerobic or anaerobic. The class of the phylum Bacteroidetes includes Bacteroidia, Chitinophagia, Cytophagia, Flavobacteria, Saprospiria, and Sphingobacteriia. In some embodiments of a composition comprising a purified bacterial strain belonging to the phylum Bacteroidetes, the bacterial strain belongs to the class Bacteroidia. In some embodiments, the composition comprises two or more bacterial strains belonging to the phylum Bacteroidetes, and the two or more bacterial strains belong to the class Bacteroidia. In some embodiments, each bacterial strain in the composition belonging to the phylum Bacteroidetes belongs to the class Bacteroidia.

[0096] Families within the phylum Bacteroidetes include Bacteroidaceae, Marinifilaceae, Tannerellaceae, Rikenellaceae, Porphyromonadaceae, Odorbacteraceae, and Prevotellaceae. In some embodiments of a composition comprising a purified bacterial strain belonging to the phylum Bacteroidetes, the bacterial strain belongs to a family selected from the group consisting of Bacteroidaceae, Marinifilaceae, Tannerellaceae, Rikenellaceae, Porphyromonadaceae, Odorbacteraceae, and Prevotellaceae. In some embodiments, the composition comprises two or more bacterial strains belonging to the phylum Bacteroidetes, wherein the two or more bacterial strains belong to families independently selected from the group consisting of Bacteroidaceae, Marinifilaceae, Tannerellaceae, Rikenellaceae, Porphyromonadaceae, Odorbacteraceae, and Prevotellaceae.

[0097] In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Bacteroidetes; one or more purified bacterial strains of an Escherichia species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Bacteroidetes; one or more purified bacterial strains of a Fusobacterium species; and taurine.

[0098] In some aspects, the present disclosure provides purified bacterial strains belonging to the Escherichia species, purified bacterial strains belonging to the Fusobacterium species, as well as Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium The present invention provides a composition comprising one or more purified bacterial strains of a species selected from the group consisting of: faecis; and taurine.

[0099] In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species, and one or more purified bacterial strains of a species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, and Phascolarctobacterium faecium; and taurine.

[0100] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the Escherichia species and one or more purified bacterial strains of a species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.

[0101] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the Fusobacterium species and one or more purified bacterial strains of a species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faeces; and taurine.

[0102] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species, and one or more purified bacterial strains of a species selected from the group consisting of Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteriodes cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.

[0103] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the species Escherichia and one or more purified bacterial strains of a species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteriodes cellulosilyticus, Bacteroides faeces, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.

[0104] In some aspects, the disclosure provides compositions comprising a purified bacterial strain belonging to the species Fusobacterium and one or more purified bacterial strains of a species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteriodes cellulosilyticus, Bacteroides faeces, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.

[0105] In some aspects, the disclosure provides a composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species; and taurine.

[0106] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, Escherichia; and taurine.

[0107] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, Fusobacterium; and taurine.

[0108] In some aspects, the disclosure provides a composition comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species; and taurine.

[0109] In some aspects, the present disclosure provides a composition comprising a purified bacterial strain belonging to the species Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, Escherichia; and taurine.

[0110] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, Fusobacterium; and taurine.

[0111] In some cases, Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613)、cf.Clostridium sp.MLG055(Erysipelotrichaceae bacterium 2_2_44A)、Clostridium indolis(Anaerostipes caccae DSM 14662)、Anaerotruncus colihominis(Anaerotruncus colihominis DSM 17241)、Ruminococcus sp.ID8(Lachnospiraceae bacterium 2_1_46FAA)、Clostridium lavalense(Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp.D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp.The present invention provides a composition comprising a purified bacterial strain belonging to the species Escherichia 316002 / 08 (Clostriales bacterium 1_7_47FAA), a purified bacterial strain belonging to the species Fusobacterium 3_1_57FAA_CT1, a purified bacterial strain belonging to the species Escherichia 316002 / 08 (Clostriales bacterium 1_7_47FAA), a purified bacterial strain belonging to the species Fusobacterium ...

[0112] In some cases, Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613)、cf.Clostridium sp.MLG055(Erysipelotrichaceae bacterium 2_2_44A)、Clostridium indolis(Anaerostipes caccae DSM 14662)、Anaerotruncus colihominis(Anaerotruncus colihominis DSM 17241)、Ruminococcus sp.ID8(Lachnospiraceae bacterium 2_1_46FAA)、Clostridium lavalense(Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp.D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp.The present invention provides a composition comprising purified bacterial strains belonging to the Escherichia species, such as Clostriales bacterium 1_7_47FAA, Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), and Escherichia sp.; and taurine.

[0113] In some cases, Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613)、cf.Clostridium sp.MLG055(Erysipelotrichaceae bacterium 2_2_44A)、Clostridium indolis(Anaerostipes caccae DSM 14662)、Anaerotruncus colihominis(Anaerotruncus colihominis DSM 17241)、Ruminococcus sp.ID8(Lachnospiraceae bacterium 2_1_46FAA)、Clostridium lavalense(Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp.D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp.The present invention provides a composition comprising purified bacterial strains belonging to the species Fusobacterium 316002 / 08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), and Fusobacterium; and taurine.

[0114] In some aspects, the disclosure provides a composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to the species Escherichia, a purified bacterial strain belonging to the species Fusobacterium; and taurine.

[0115] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, Escherichia; and taurine.

[0116] In some aspects, the disclosure provides a composition comprising a purified bacterial strain belonging to the species Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, Fusobacterium; and taurine.

[0117] In some aspects, the present disclosure relates to Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comest, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faeci, a purified bacterial strain belonging to the Escherichia species, a purified bacterial strain belonging to the Fusobacterium species; and taurine.

[0118] In some aspects, the present disclosure relates to Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteriodes cellulosilyticus, Bacteroides uniformis, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Alistipes shahii, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecis, a purified bacterial strain belonging to the species Escherichia, a purified bacterial strain belonging to the species Fusobacterium; and taurine.

[0119] In some aspects, the disclosure provides a composition comprising Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteriodes xyalinosolvens, Bacteroides caccae, Bacteriodes cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Alistipes putredinis, Alistipes shahii, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, a purified bacterial strain belonging to the species Escherichia, a purified bacterial strain belonging to the species Fusobacterium; and taurine.

[0120] In some embodiments, the present disclosure provides a composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.

[0121] In some embodiments, the present disclosure provides a composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Clostridium clostridioforme, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.

[0122] In some embodiments, the present disclosure provides a composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.

[0123] In some embodiments, the present disclosure provides a composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.

[0124] In some embodiments, the present disclosure provides a composition comprising Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.

[0125] In some embodiments, the present disclosure provides a composition comprising Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Clostridium citroniae, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Escherichia coli; and taurine.

[0126] In some embodiments, the present disclosure provides a composition comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.

[0127] In some embodiments, the present disclosure provides a composition comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Fusobacterium mortiferum, Escherichia coli; and taurine.

[0128] In some embodiments, the present disclosure provides a composition comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.

[0129] In some aspects, the disclosure provides a composition comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.

[0130] In some aspects, the disclosure provides compositions comprising one or more purified bacterial strains of the species Bacteroides vulgatus, Clostridium citroniae, and Phascolarctobacterium faecium, and a species selected from the group consisting of Bacteroides faecis, Bacteroides ovatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Agathobaculum butyriciproducens, Fusobacterium mortiferum, and Escherichia coli; and taurine.

[0131] In some aspects, the disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides faecis, Bacteroides vulgatus, Odoribacter splanchnicus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.

[0132] In some aspects, the disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.

[0133] In some aspects, the disclosure provides a composition comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.

[0134] In some aspects, the disclosure provides compositions comprising a purified bacterial mixture including bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae. In some aspects, the disclosure provides compositions comprising a purified bacterial mixture consisting of bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae. In some aspects, the disclosure provides compositions comprising bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae; and taurine. In some aspects, the disclosure provides compositions comprising taurine and a purified bacterial mixture consisting of bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae. In some embodiments, the Bacteroides faecis bacterial strain comprises a 16S rDNA sequence comprising at least 97% sequence identity to the nucleic acid sequence of SEQ ID NO: 30. In some embodiments, the Bacteroides vulgatus bacterial strain comprises a 16S rDNA sequence comprising at least 97% sequence identity to the nucleic acid sequence of SEQ ID NO: 10. In some embodiments, the Phascolartcobacterium faecium bacterial strain comprises a 16S rDNA sequence comprising at least 97% sequence identity to the nucleic acid sequence of SEQ ID NO: 36. In some embodiments, the Clostridium citroniae bacterial strain comprises a 16S rDNA sequence comprising at least 97% sequence identity to the nucleic acid sequence of SEQ ID NO: 29.

[0135] In some aspects, the disclosure provides a composition comprising a purified bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36. In some aspects, the disclosure provides a composition comprising a purified bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36; and taurine. In some aspects, the disclosure provides a composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36. In some aspects, the disclosure provides a composition comprising taurine and a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36.

[0136] In some embodiments, any of the compositions described herein further comprises one or more strains selected from the group consisting of Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.

[0137] As will be appreciated by one of skill in the art, any one or more bacterial strains identified as having pathogen-antagonizing activity may be included in any of the compositions described herein.

[0138] Aspects of the present disclosure relate to bacterial strains having a 16S rDNA sequence that has sequence identity to the nucleic acid sequence of any one of the bacterial strain or species sequences described herein. 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 amino acid residues or nucleotides that are 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% sequence identity) over a comparison window, or over a designated region of the nucleic acid or amino acid sequence, or over the entire sequence, when compared and aligned for maximum correspondence over a 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 that is at least about 50 nucleotides in length, or more preferably over a region that is 100 to 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.

[0139] In some embodiments, the bacterial strain has at least 60%, at least 70%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or up to 100% sequence identity to any of the strains or bacterial species described herein over a designated region or entire sequence. It will be understood by those of skill in the art that the term "sequence identity" or "percent sequence identity" 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 portions thereof.

[0140] Additionally, or alternatively, two or more sequences may be assessed for alignment between the 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. When compared over a comparison window or designated region and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection, two sequences are "substantially aligned" if they have a specified percentage of amino acid residues or nucleotides that are the same over the designated region or over the entire sequence (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% identical). Optionally, the alignment exists over a region that is at least about 50 nucleotides in length, or more preferably over a region that is 100 to 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.

[0141] For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. Methods of alignment of sequences for comparison are well known in the art. See, for example, the local homology algorithm of Smith and Waterman (1970) Adv. Appl. Math. 2:482c, the homology alignment algorithm of Needleman and Wunsch, J. Mol. Biol. (1970) 48:443, the similarity search method of Pearson and Lipman, Proc. Natl. Acad. Sci. USA 85:2444, 1988, 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, for example, Brent et al., Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (Ringbou ed., 2003)). Two examples of algorithms that are suitable for determining percent sequence identity and percent sequence similarity are BLAST and BLAST 2.0, described in Altschul et al., Nuc. Acids Res. 25:3389-3402, 1977; and Altschul et al., J. Mol. Biol. 215:403-410, 1990, respectively.

[0142] In one aspect, the bacterial composition includes two or more (e.g., 2, 3, 4, 5 or more) purified bacterial strains comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to a nucleic acid sequence selected from SEQ ID NOs: 1-83. In one aspect, the bacterial composition comprises two or more (e.g., two, three, four, five or more) purified bacterial strains comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to a nucleic acid sequence selected from SEQ ID NOs: 1-83. In one aspect, the bacterial composition consists essentially of two or more (e.g., two, three, four, five or more) purified bacterial strains comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to a nucleic acid sequence selected from SEQ ID NOs: 1-83.

[0143] In one aspect, the bacterial composition includes two or more (e.g., 2, 3, 4, 5 or more) purified bacterial strains comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to a nucleic acid sequence selected from SEQ ID NOs: 1-47. In one aspect, the bacterial composition comprises two or more (e.g., two, three, four, five or more) purified bacterial strains comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to a nucleic acid sequence selected from SEQ ID NOs: 1-47. In one aspect, the bacterial composition consists essentially of two or more (e.g., two, three, four, five or more) purified bacterial strains comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to a nucleic acid sequence selected from SEQ ID NOs: 1-47.

[0144] In some embodiments, the compositions disclosed herein comprise two or more bacterial strains. In 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, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47 or more bacterial strains (e.g., purified bacterial strains).

[0145] In some embodiments, the bacterial composition comprises a purified bacterial strain comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to the nucleic acid sequence provided by SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists of a purified bacterial strain comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to the nucleic acid sequence of SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists essentially of a purified bacterial strain comprising a 16S rDNA sequence having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to a nucleic acid sequence of SEQ ID NO: 1-47.

[0146] In some embodiments, the bacterial composition comprises 38 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to any of the nucleic acid sequences provided by SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists of 38 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to any of the nucleic acid sequences of SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists essentially of 38 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to any of the nucleic acid sequences of SEQ ID NOs: 1-47.

[0147] In some embodiments, the bacterial composition comprises 33 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to any of the nucleic acid sequences provided by SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists of 33 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to any of the nucleic acid sequences of SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists essentially of 33 purified bacterial strains containing 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity to any of the nucleic acid sequences of SEQ ID NOs: 1-47.

[0148] Provided herein are bacterial strains and combinations of bacterial strains that are homologous or have a high percentage of homology to bacterial strains comprising a 16S rDNA sequence selected from SEQ ID NOs: 1 to 83. It is understood that the bacterial strains described herein have a 16S rDNA sequence selected from SEQ ID NOs: 1 to 83 and may also be homologous to other strains based on their entire genome sequences or subsets of their entire genome sequences.

[0149] In one aspect, the composition comprises a fraction of a fecal sample. In some embodiments, the composition comprises a non-sporulating fraction of a fecal sample. In some embodiments, the composition comprises a sporulating fraction of a fecal sample.

[0150] In some embodiments, the compositions described herein comprise spore-forming and non-spore-forming bacterial strains. In some embodiments, the compositions described herein comprise spore-forming bacterial strains. In some embodiments, the compositions described herein comprise only spore-forming bacterial strains. In some embodiments, the compositions described herein comprise only non-spore-forming bacterial strains. Spore-forming bacteria can be in a spore form (i.e., as spores) or a vegetative form (i.e., as vegetative cells). In the spore form, bacteria are generally more resistant to environmental conditions such as heat, acid, radiation, oxygen, chemicals, and antibiotics. In contrast, in a vegetative or actively growing state, bacteria are more susceptible to such environmental conditions compared to the spore form. Generally, bacterial spores can germinate from the spore form to a vegetative / actively growing state under appropriate conditions. For example, spore-form bacteria can germinate when introduced into the intestine.

[0151] In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is a sporulating agent. In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is in spore form. In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is a non-sporulating agent. In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is in vegetative form. As described above, spore-forming bacteria can be in vegetative form. In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is in spore form, and at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is in vegetative form. In some embodiments, at least one bacterial strain believed to be capable of forming spores (i.e., a sporulating agent) is present in the composition in vegetative form. In some embodiments, at least one bacterial strain believed to be capable of forming spores is present in the composition in both spore and vegetative form.

[0152] In some embodiments, the composition comprises a bacterial strain that is a spore-forming bacterial strain. In some embodiments, the composition comprises a bacterial strain that is a non-spore-forming bacterial strain. In some embodiments, the composition comprises a bacterial strain that is a spore-forming bacterial strain and a bacterial strain that is a non-spore-forming bacterial strain. In some embodiments, the composition comprises a mixture of bacterial strains, wherein at least 10% of the bacterial strains are spore-forming bacterial strains, at least 20% of the bacterial strains are spore-forming bacterial strains, at least 30% of the bacterial strains are spore-forming bacterial strains, at least 40% of the bacterial strains are spore-forming bacterial strains, at least 50% of the bacterial strains are spore-forming bacterial strains, at least 60% of the bacterial strains are spore-forming bacterial strains, at least 70% of the bacterial strains are spore-forming bacterial strains, at least 80% of the bacterial strains are spore-forming bacterial strains, at least 90% of the bacterial strains are spore-forming bacterial strains, or up to 100% of the bacterial strains are spore-forming bacterial strains. Whether a bacterial strain is a spore-forming strain can be determined, for example, by evaluating the bacterial strain's genome for the presence of spore formation genes. However, it should be understood that not all bacteria predicted to encode sporulation genes can be made to sporulate. Furthermore, whether a bacterial strain is a sporulating strain can be determined by exposing the bacterial strain to stress conditions, such as exposure to heat or chemicals known to induce sporulation (e.g., ethanol or chloroform).

[0153] It should be understood that spore-forming bacteria can be in spore form or vegetative form. In some embodiments of the compositions provided herein, the spore-forming bacteria are in spore form. In some embodiments, the spore-forming bacteria are in vegetative form. In some embodiments, the spore-forming bacteria exist in both spore form and vegetative form. In some embodiments, the composition comprises spore-forming bacteria, wherein at least 10% of the spore-forming bacteria are in spore form, at least 20% of the spore-forming bacteria are in spore form, at least 30% of the spore-forming bacteria are in spore form, at least 40% of the spore-forming bacteria are in spore form, at least 50% of the spore-forming bacteria are in spore form, at least 60% of the spore-forming bacteria are in spore form, at least 70% of the spore-forming bacteria are in spore form, at least 80% of the spore-forming bacteria are in spore form, at least 90% of the spore-forming bacteria are in spore form, or up to 100% of the spore-forming bacteria are in spore form.

[0154] It is envisioned that the bacterial strains in the compositions provided herein are viable and will remain viable upon reaching the target area (e.g., the intestine). Bacterial spores are considered viable in this regard. In some embodiments, bacteria administered as spores may germinate in the target area (e.g., the intestine). It should be further understood that not all bacteria are viable, and that the composition may include a non-viable percentage (e.g., by weight). Furthermore, in some embodiments, the composition includes bacterial strains that are not viable at the time of administration or when the composition reaches the target area (e.g., the intestine). It is envisioned that non-viable bacteria may still be useful by providing some nutrients and metabolic products to other bacterial strains in the composition.

[0155] Methods for inducing sporulation in spore-forming bacterial strains are well known in the art (see, for example, Paredes-Sabja et al., Trends Microbiol. (2011) 19(2):85-94). Generally, sporulating bacterial strains can be brought into spore form by stressing the bacterial strain. Non-limiting examples of stresses that can induce sporulation include an increase in temperature, a change in available nutrients, and / or exposure to chemicals (e.g., ethanol or chloroform). It should be noted that bacteria that are non-sporulators, for example, because they lack sporulation genes, cannot be induced to sporulate by stress. To prepare a composition in which all bacterial strains are in spore form, the composition or the bacterial culture used to prepare the composition can be subjected to a treatment to kill any bacteria that are not in spore form (e.g., vegetative forms), for example, by exposing the composition to heat and chemically destroying non-sporulating bacteria. Subsequently, the spore-form bacteria can be separated from the non-sporulating bacteria, for example, by filtration.

[0156] Spore abundance can be quantified using techniques known in the art. These techniques include phase-contrast microscopy and counting spores using a hemocytometer. Furthermore, spore viability can be determined by seeding and growing spores. For example, spores can be seeded on an appropriate medium and incubated in an anaerobic chamber for a period of time (e.g., 48-96 hours). Viability can then be determined by quantifying the colony-forming units corresponding to germinated spores. For example, spores can be plated on TCCFA (taurocholate, cycloserine, cefoxintin, fructose agar) plates, where taurocholate supports spore germination. Furthermore, spores can be quantified using the dipicolinic acid assay (DPA assay). DPA is a spore-selective agent and a clear indicator of endospores. When complexed with terbium, a bright green luminescence is observed.

[0157] In some embodiments, the composition comprises a bacterial strain that is a non-spore-forming bacterial strain. In some embodiments, the composition comprises a bacterial strain that is a spore-forming bacterial strain and a bacterial strain that is a non-spore-forming bacterial strain. In some embodiments, the composition comprises a mixture of bacterial strains, wherein at least 10% of the bacterial strains are non-spore-forming bacterial strains, at least 20% of the bacterial strains are non-spore-forming bacterial strains, at least 30% of the bacterial strains are non-spore-forming bacterial strains, at least 40% of the bacterial strains are non-spore-forming bacterial strains, at least 50% of the bacterial strains are non-spore-forming bacterial strains, at least 60% of the bacterial strains are non-spore-forming bacterial strains, at least 70% of the bacterial strains are non-spore-forming bacterial strains, at least 80% of the bacterial strains are non-spore-forming bacterial strains, at least 90% of the bacterial strains are non-spore-forming bacterial strains, or up to 100% non-spore-forming bacterial strains.

[0158] In any of the compositions provided herein, the bacterial strain may be purified. In any of the compositions provided herein, the bacterial strain may be isolated. Any of the bacterial strains described herein may be isolated and / or purified from a source, such as a culture or a microbiota sample (e.g., feces). The bacterial strains used in the compositions provided herein are generally isolated from the microbiota of a healthy individual. However, bacterial strains may also be isolated from individuals considered unhealthy. In some embodiments, the composition includes strains derived from multiple individuals.

[0159] As used herein, the term "isolated" refers to a bacterium or bacterial strain that has been separated from one or more undesirable components, such as another bacterium or bacterial strain, one or more components of a growth medium, and / or one or more components of a sample, such as a fecal sample. In some embodiments, the bacterium is substantially isolated from a source such that other components of the source are not detectable.

[0160] Also, as used herein, the term "purified" refers to a bacterial strain or composition that has been separated from one or more components, such as contaminants. In some embodiments, the bacterial strain is substantially free of contaminants. In some embodiments, one or more bacterial strains of a composition may be purified independently from one or more other bacteria produced and / or present in a culture or sample containing the bacterial strain. In some embodiments, the bacterial strain is isolated or purified from a sample and then cultured under appropriate conditions for bacterial replication, e.g., anaerobic culture conditions. Bacteria grown under appropriate conditions for bacterial replication may then be isolated / purified from the culture in which they were grown.

[0161] In some embodiments, the bacterial strain of the compositions provided herein is an obligate anaerobe. In some embodiments, the bacterial strain of the compositions provided herein is an obligate anaerobe.

[0162] Aspects of the present disclosure relate to methods for inhibiting undesirable bacteria. As used herein, the term "inhibit" refers to any form of inhibiting undesirable bacteria. In some embodiments, the methods described herein reduce / inhibit or prevent colonization, replication, growth, and / or survival of undesirable bacteria (e.g., pathogenic organisms, multidrug-resistant organisms, such as carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae). In some embodiments, the methods described herein directly or indirectly induce the death of undesirable bacteria (e.g., pathogenic organisms, multidrug-resistant organisms, such as carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae).

[0163] Aspects of the present disclosure relate to methods for inhibiting infection by a pathogenic organism in a subject. Aspects of the present disclosure relate to methods for reducing or preventing colonization by a pathogenic organism (e.g., bacteria, virus, fungus, or parasite) in a subject. Aspects of the present disclosure relate to methods for treating infection by a pathogenic organism. In some embodiments, the pathogenic organism is not multidrug resistant. In some embodiments, the pathogenic organism is resistant to one or more drugs (e.g., antibacterial agents, antiviral agents, antifungal agents). In some embodiments, the pathogenic organism is multidrug resistant. The methods described herein involve administering a therapeutically effective amount of any of the compositions described herein to a subject. As used herein, "subject," "individual," and "patient" are used interchangeably and refer to a vertebrate, preferably a mammal such as a human. Mammals include, but are not limited to, human primates, non-human primates, or murine, bovine, equine, canine, or feline species. In some embodiments, the subject is human.

[0164] In some embodiments, any of the compositions described herein is effective in inhibiting the replication, survival, and / or colonization of one or more pathogenic organisms. In some instances, the pathogenic organism is susceptible to an antibiotic, while in other instances, the pathogenic organism is resistant to an antibiotic. In some embodiments, the pathogenic organism is a multidrug-resistant organism described elsewhere herein. In some embodiments, the pathogenic organism is an oral microbiota bacterium. Note that oral microbiota bacteria are not necessarily pathogenic, but may become pathogenic when located elsewhere, such as in the gastrointestinal tract. The amount of inhibition of replication, survival, and / or colonization of one or more pathogenic organisms can be measured or determined using standard assays known in the art, some of which are further described and exemplified herein.

[0165] In some embodiments, administration of the compositions described herein reduces / inhibits or prevents the colonization, recolonization, replication, growth and / or survival of pathogenic organisms, such as multidrug-resistant organisms. In some embodiments, administration of the compositions described herein allows colonization of the subject's gastrointestinal tract by the bacterial strain(s) of the composition, thereby preventing colonization by multidrug-resistant organisms.

[0166] In some embodiments, the pathogenic organism is a pathogenic commensal, i.e., a potentially pathogenic organism that survives as a commensal under normal circumstances.

[0167] In some embodiments, the subject is a carrier of a multidrug-resistant organism and is affected by the infection. In some embodiments, the subject is an asymptomatic carrier of a multidrug-resistant organism. In some embodiments, the subject is experiencing recurrent or chronic colonization with a multidrug-resistant organism. In some embodiments, the subject is suffering from an initial outbreak of a particular multidrug-resistant organism. In some embodiments, the subject is at risk for colonization with a multidrug-resistant organism, such as previous antibiotic use. In some embodiments, the subject has risk factors associated with colonization with a multidrug-resistant organism. In some embodiments, the subject has had a previous infection or colonization with a multidrug-resistant organism. In some embodiments, the subject has been treated with an antibiotic that resulted in a recurrence of the multidrug-resistant organism.

[0168] In some embodiments, the subject is undergoing a procedure that places the subject at a higher risk of colonization, and the composition is administered prophylactically. In some embodiments, the subject has a disease or disorder associated with the use of a proton pump inhibitor that may increase the likelihood of oral bacteria migrating to the intestine. In some embodiments, the compositions provided herein are administered to a subject to reduce the risk of colonization with multidrug-resistant organisms. In some embodiments, the bacterial compositions provided herein are administered to a subject receiving a proton pump inhibitor.

[0169] Individuals may be at risk of acquiring multidrug-resistant organisms if they have recently received antimicrobial agents, are immunosuppressed (e.g., chemotherapy, have a malignant tumor, or have undergone or have undergone a transplant), have a chronic disease or inflammatory condition (e.g., diabetes, kidney disease, etc.), are elderly, undergo hemodialysis, surgery, or other invasive procedures, have indwelling devices, and / or live in a long-term care facility or are hospitalized. In some embodiments, the subject is colonized with multidrug-resistant organisms. While colonization of the skin and mucous membranes is common (Cassone et al., Curr Geriatr Rep. (2015) 4(1):87-89), multidrug-resistant organisms can also colonize the gastrointestinal (GI) tract and oral cavity, causing inflammation (Atarashi et al., Science (2017) 358, 359-365). Colonization can cause serious infections of the skin, lungs, urinary tract, or bloodstream, resulting in serious complications, including death (CDC, 2013). In some cases, multidrug-resistant organisms can be ingested, leading to consequences throughout the digestive system. In some embodiments, multidrug-resistant organisms can colonize the oral cavity.

[0170] In some embodiments, the multidrug-resistant organism is vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacteriaceae (CRE), Neisseria gonorrhea, multidrug-resistant Acinetobacter, Campylobacter, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, ESBL-producing Escherichia coli, multidrug-resistant Pseudomonas aeruginosa, Salmonella, drug-resistant non-enteric Salmonella, drug-resistant Salmonella Typhi, drug-resistant Shigella, methicillin-resistant Staphylococcus aureus, drug-resistant Streptococcus pneumoniae, drug-resistant Mycobacterium tuberculosis, vancomycin-resistant Staphylococcus aureus, erythromycin-resistant Group A Streptococcus, or clindamycin-resistant Group B Streptococcus. In some embodiments, the multidrug-resistant organism is vancomycin-resistant Enterococcus (VRE). In some embodiments, the multidrug-resistant organism is a carbapenem-resistant Enterobacteriaceae (CRE).

[0171] In some embodiments, the compositions described herein are effective in reducing or preventing colonization by two or more multidrug-resistant organisms. In some embodiments, the compositions described herein are effective in treating infections by two or more multidrug-resistant organisms. For example, in some embodiments, the compositions described herein are effective in reducing, preventing, or treating infections by carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.

[0172] Enterobacteriaceae is a broad bacterial family that encompasses many bacterial pathogens. Bacteria belonging to the Enterobacteriaceae are characterized as Gram-negative and are frequently found in the intestinal flora of the intestinal tract of humans and mammals, but can also be found in water and soil. Non-limiting examples of bacterial genera belonging to Enterobacteriaceae include Alishewanella, Buttiauxella, Grimontella, Pectobacterium, Salmonella, Yokenella, Alterococcus, Cedecea, Hafnia, Phlomobacter, Samsonia, Aquamonas, Citrobacter, Klebsiella, Photorhabdus, Serratia, Alanicola, Cronobacter, Kluyvera, Poodoomaamaana, S higella, Arsenophonus, Dickeya, Leclercia, Plesiomonas, Sodalis, Azotivirga, Edwardsiella, Leminorella, Pragia, Tatumella, Blochmannia, Enterob acter, Moellerella, Proteus, Trabulsiella, Brenneria, Erwinia, Morganella, Providencia, Wigglesworthia, Buchnera, Escherichia, Obesumbacterium Includes Rahnella, Xenorhabdus, Budvicia, Ewingella, Pantoea, Raoultella, and Yersinia.

[0173] In some embodiments, the compositions described herein are effective in reducing, preventing, or treating infections caused by carbapenem-resistant Enterobacteriaceae (CRE). As used herein, the term "carbapenem-resistant Enterobacteriaceae" or "CRE" refers to a bacterial strain or species that belongs to the Enterobacteriaceae family and has developed resistance to carbapenem antibiotics. In some embodiments, the CRE is resistant to additional antibiotics in addition to carbapenem antibiotics.

[0174] In some embodiments, the carbapenem-resistant Enterobacteriaceae is carbapenem-resistant Klebsiella pneumoniae. An example of a CRE Klebsiella pneumoniae is Klebsiella pneumoniae strain ATCC 700721.

[0175] In some embodiments, the compositions described herein are effective in reducing, preventing, or treating infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. As used herein, the term "extended-spectrum beta-lactamase-producing Enterobacteriaceae" or "ESBL-Enterobacteriaceae" refers to a bacterial strain or species that belongs to the Enterobacteriaceae family and produces or is capable of producing beta-lactamase enzymes that degrade or inactivate antibiotics. In some embodiments, the ESBL Enterobacteriaceae is resistant to one or more antibiotics (e.g., beta-lactam antibiotics). In some embodiments, the ESBL Enterobacteriaceae is resistant to additional antibiotics in addition to beta-lactam antibiotics.

[0176] In some embodiments, the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae or ESBL-producing E. coli. In some embodiments, the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae subsp. pneumoniae (ATCC 700721), ESBL-producing E. coli ATCC BAA 2777, adherent / invasive E. coli (AIEC), Shiga toxin-producing E. coli (STEC), Verocytotoxin-producing E. coli (VTEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), or diffusely adherent E. coli (DAEC).

[0177] In some embodiments, the CRE- or ESBL-producing Enterobacteriaceae is Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter sakasakii, Escherichia coli, Escherichia albertii, Proteus mirabilis, Proteus vulgaris, Salmonella enterica, Serratia marcescens, Shigella dysenterii, Shigella flexneri, Shigella sonnei, Shigella boydii, Yersinia pestis, Yersinia enterocolitica, or Yersinia pseudotuberculosis.

[0178] Aspects of the present disclosure relate to methods for inhibiting pathogenic organisms in a subject. In some embodiments, the pathogenic organisms are susceptible to antibiotics (e.g., are not multidrug-resistant organisms). Pathogenic organisms are organisms that can cause disease in a subject and can be viruses, bacteria, fungi, protozoa, and helminths. Non-limiting examples of pathogenic organisms of the present disclosure include Salmonella, Shigella, Staphylococcus, Streptococcus, Enterococcus, Enterobacteriaceae, Neisseria gonorrheae, Acinetobacter, Campylobacter, Clostridium, Listeria, Escherichia, Pseudomonas aeruginosa, Salmonella, Shigella, Staphylococcus aureus, Streptococcus pneumoniae, Tuberculosis, Group A Streptococcus, or Group B Streptococcus, Toxoplasma, Cyclospora, Giardia, Cryptosporidium, and Trichinella.

[0179] In some embodiments, the pathogenic organism in the subject is resistant to treatment with a drug. In some embodiments, the pathogenic organism in the subject is resistant to treatment with multiple drugs (e.g., multidrug resistance). Drugs that may be used to treat pathogenic organisms of the present disclosure may include antibiotics, antivirals, antifungals, and antiparasitics.

[0180] In some embodiments, a pathogenic organism that is sensitive to a drug may acquire resistance to one or more drugs. In some embodiments, a pathogenic organism that is sensitive to an antibiotic may acquire resistance to one or more antibiotics. In some embodiments, a pathogenic organism is resistant to one or more drugs (e.g., antibiotics) and may acquire resistance to one or more drugs (e.g., antibiotics). In some embodiments, a pathogenic organism is resistant to one or more drugs (e.g., antibiotics) and may become a multidrug-resistant organism by acquiring resistance to two or more drugs (e.g., antibiotics).

[0181] Generally, there are multiple ways in which an organism may acquire drug resistance. In some embodiments, an organism may acquire drug resistance by acquiring a mutation in its genome that promotes the organism's survival in the presence of at least one drug. In some embodiments, an organism acquires DNA from an organism that is resistant to one or more drugs (e.g., antibiotics), thereby becoming resistant to the drug (e.g., antibiotic). In some embodiments, an organism acquires a plasmid, such as a plasmid containing one or more drug (e.g., antibiotic) resistance genes, from an organism that is resistant to one or more drugs (e.g., antibiotics), thereby becoming resistant to the drug (e.g., antibiotic).

[0182] In some embodiments, administration of a composition described herein reduces / inhibits or prevents intestinal colonization by oral microbiota bacteria. In some embodiments, administration of a composition described herein reduces / inhibits or prevents colonization, replication, growth, and / or survival of oral microbiota bacteria in the intestinal tract of a subject. In some embodiments, administration of a composition described herein allows colonization of the subject's digestive tract by the bacterial strain(s) of the composition, thereby preventing colonization by oral microbiota bacteria.

[0183] In some embodiments, the subject is a carrier of oral bacteria and is affected by infection. In some embodiments, the subject is an asymptomatic carrier of oral bacteria. In some embodiments, the subject is experiencing recurrent or chronic oral bacterial colonization. In some embodiments, the subject is at risk for oral bacterial colonization. In some embodiments, the subject has risk factors associated with oral bacterial colonization. In some embodiments, the subject is taking a proton pump inhibitor. In some embodiments, the subject has had a previous infection or colonization with oral bacteria.

[0184] In some embodiments, the subject will undergo a procedure that places the subject at higher risk of colonization, and the composition is administered prophylactically. In some embodiments, the compositions provided herein are administered to a subject to reduce the risk of oral bacterial colonization.

[0185] More than 700 bacterial species or phylotypes have been found in the oral cavity, but over 50% have not yet been cultivated. Numerous phyla have been identified in the oral microbiome: Actinobacteria, Arachnia, Bacteroidetes, Bifidobacterium, Chlamydiae, Chloroflexi, Eubacterium, Euryarchaeota, Fusobacterium, Firmicutes, Fusobacteria, Lactobacillus, Leptotrichia, Peptococcus, Peptostreptococcus, Propionibacterium, Proteobacteria, Selenomonas, Spirochaetes, SR1, Synergistetes, Tenericutes, Treponema, TM7, and Veillonella (Dewhirst et al., J. Bacteriology (2010) 192(19):5002-5010). Examples of oral microbiota bacteria include, but are not limited to, Streptococcus sanguis, Streptococcus salivarius, Streptococcus mitis, Streptococcus mutans, Treponema denticola, Eikenella corrodens, Streptococcus gordonii, Streptococcus oralis, Acinomyces maeslundii, and Bacteroides melaningenicus. A list of exemplary species found in the human oral cavity can be found in the Human Oral Microbiome Database (homd.org). In some embodiments, oral microbiota bacteria can be pathogenic. In some embodiments, oral microbiota bacteria can be pathogenic if the bacteria gain access to another part of the body. In some embodiments, oral microbiota bacteria are not pathogenic.

[0186] In some embodiments, administration of the compositions described herein reduces / inhibits or prevents intestinal colonization by oral microbiota bacteria. In some embodiments, the oral microbiota bacteria is Fusobacterium nucleatum (see, e.g., Yoneda et al. J Gastrointest Dig Syst (2016) 6:2). In some embodiments, the oral microbiota bacteria is Campylobacter concisus (see, e.g., Yoneda et al. J Gastrointest Dig Syst (2016) 6:2). In some embodiments, the oral microbiota bacteria is Streptococcus mutans (see, e.g., Yoneda et al. J Gastrointest Dig Syst (2016) 6:2).The active ingredients of the active ingredients are Rothia mucilaginosa, Neisseria subflava, Granulicatella para-adiacens, Streptococcus salivarius, Streptococcus mitis, and Fusobacterium sp.1_1_41FAA、Streptococcus oralis、Streptococcus salivarius、Neisseria subflava、Prevotella scopos、Veillonella parvula、Streptococcus sp.M143、Haemophilus parainfluenzae、Prevotella sp.CD3_34、Neisseria macacae、Prevotella histicola、Prevotella pallens、Streptococcus infantis、Streptococcus parasanguinis、Porphyromonas CW034、Streptococcus sp.oral strain T1-E5、Twin sp.933-88, Veillonella parvula and Prevotella sp.C561 are listed in table S1A of Atarashi et al.

[0187] In some embodiments, intestinal colonization with oral microbiota bacteria induces a Th1 immune response in a subject. Examples of oral microbiota bacteria that can induce a Th1 immune response have been isolated and show significant similarity (≧96.3%) to the following species: Mogibacterium sp. CM96, Peptostreptococcus stomatis, Bifidobacterium sp. Group III-3, Slackia exigua, Veillonella denticariosi, Atopobium parvulum, Veillonella sp. 2011_oral_VSA_A3, Campylobacter concisus, Actinomyces odontolyticus, Solobacterium moorei, Enterococcus faecium, Bifidobacterium dentium, Veillonella parvela, Fusobacterium sp. 3_1_33, Klebsiella aeromobilis, and Klebsiella pneumoniae (see, e.g., Atarashi et al., J. Immunol. 2011, 2011, 2011). al., Science (2017) 358:359-365, Schirmer et al., Cell Host and Microbe (2018) 24:600-610).

[0188] In some embodiments, the bacteria that induce a Th1 immune response in a subject (e.g., IBD) are pathogens. "Pathogen" refers to potentially pathogenic (disease-causing) organisms that live as commensals under normal circumstances. Examples of pathogens include bacteria associated with chronic inflammatory conditions (e.g., IBD). Non-limiting examples of pathogens include Shigella spp., Campylobacter spp., Cryptosporidium spp., Salmonella spp., Escherichia coli strains (for example, Enteropathogenic E.coli, Enteroaggregative E.coli, Enterotoxigenic E.coli), Veillonella dispar, Aggregatibacter segnis, Campylobacter, Lachnospiraceae, Veillonella parvula, Haemophilus parainfluenzae, Megasphaera, Escherichia coli, Enterobacteriaceae spp., Enterococcus spp., Fusobacterium spp., Gemella spp., Veillonella spp., Pasteurella spp., Neisseria spp., Haemophilus spp., Campylobacter spp., and Bifidobacterium spp.

[0189] In some embodiments, the method can involve determining whether oral bacteria are present in the subject. In some embodiments, the method can involve determining whether oral bacteria colonize the oral cavity of the subject. In some embodiments, if oral bacteria are present in the oral cavity of the subject, the subject can be at risk for intestinal colonization. In some embodiments, the method can involve administering a combination described herein to the subject if oral bacteria are detected in the oral cavity of the subject.

[0190] In some embodiments, the methods may involve determining whether oral bacteria are present in the gut of the subject, hi some embodiments, the methods involve administering a combination described herein to the subject if oral bacteria are detected in the gut of the subject.

[0191] In some embodiments, the method is for treating a disease or disorder associated with bacterial colonization in a subject. In some embodiments, the method is for treating a disease or disorder associated with a bacterially induced immune response in a subject. In some embodiments, the method is for treating a disease or disorder associated with a bacterially induced unwanted immune response in a subject.

[0192] In some embodiments, the method can involve determining whether a subject is colonized by bacteria. In some embodiments, the method can involve determining whether a subject has or is experiencing an immune response induced by bacterial colonization. In some embodiments, if a subject is colonized by bacteria, the subject can be at risk for an immune response induced by bacterial colonization. In some embodiments, the method can involve administering a combination described herein to the subject if it is determined that the subject is colonized by bacteria. In some embodiments, the method can involve administering a combination described herein to the subject if it is determined that the subject is experiencing or has experienced an immune response induced by bacterial colonization.

[0193] In some embodiments, the immune response induced by bacterial colonization is a Th1 immune response. As will be apparent to one of skill in the art, a Th1 immune response is mediated by a Th1 population of CD4+ cells. Th1 cells produce IFN-γ and other pro-inflammatory factors. Differentiation of CD4+ cells into Th1 cells is promoted by the presence of IL-2 and / or IL-12 and activation of the transcription factors STAT4 and T-bet. In some embodiments, the immune response induced by bacterial colonization is a Th1 pro-inflammatory response. Any direct or indirect measure of a Th1 immune response, such as the amount of IFN-γ or the number of Th1 cells, may be used to assess the level or degree of the immune response in a sample from a subject.

[0194] In some embodiments, the compositions provided herein are administered to a subject when the subject has an autoimmune disease.Examples of autoimmune diseases include inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, sprue, autoimmune arthritis, rheumatoid arthritis, graft-versus-host disease, type I diabetes, multiple sclerosis, osteoarthritis, juvenile chronic arthritis, Lyme disease arthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy, systemic lupus erythematosus, insulin-dependent diabetes mellitus, thyroiditis, asthma, psoriasis, scleroderma, atopic dermatitis, sarcoidosis, atherosclerosis, disseminated intravascular coagulation, Kawasaki disease, Graves' disease, renal syndrome, chronic fatigue syndrome, Wegener's granulomatosis, Henoch-Schoenlejn purpura, renal microvasculitis, chronic active Hepatitis, uveitis, cachexia, acute transverse myelitis, Huntington's disease, Parkinson's disease, Alzheimer's disease, stroke, primary biliary cirrhosis, hemolytic anemia, polyglandular deficiency type I syndrome and polyglandular deficiency type II syndrome, Schmidt's syndrome, adult (acute) respiratory distress syndrome, alopecia, alopecia areata, seronegative arthropathy, arthropathy, Reiter's disease, psoriatic arthropathy, chlamydia-, Yersinia- and Salmonella-associated arthropathy, spondyloarthropathy, atherosclerosis / arteriosclerosis, pemphigus vulgaris, pemphigus foliaceus, pemphigoid, type 1 IgA disease, autoimmune hemolytic anemia, Coombs-positive hemolytic anemia, acquired pernicious anemia, juvenile pernicious anemia, myalgic encephalitis / Royal encephalitisFree's disease, chronic mucocutaneous candidiasis, giant cell arteritis, primary sclerosing hepatitis, latent autoimmune hepatitis, acquired immune deficiency syndrome, acquired immune deficiency-related disease, general diverse immune deficiency (common variable hypogammaglobulinemia), dilated cardiomyopathy, fibrotic lung disease, latent fibrosing alveolitis, postinflammatory interstitial pneumonia, connective tissue disease-associated interstitial lung disease, mixed connective tissue disease-associated lung disease, systemic sclerosis-associated interstitial lung disease, rheumatoid arthritis-associated interstitial lung disease, systemic lupus erythematosus-associated lung disease, skin Dermatomyositis / polymyositis-associated lung disease, Sjögren's disease-associated lung disease, ankylosing spondylitis-associated lung disease, vasculitic diffuse lung disease, hemosiderosis-associated lung disease, drug-induced interstitial lung disease, radiation fibrosis, bronchiolitis obliterans, chronic eosinophilic pneumonia, lymphocytic infiltrative lung disease, post-infectious interstitial lung disease, gouty arthritis, autoimmune hepatitis, type 1 autoimmune hepatitis (classic autoimmune or lupoid hepatitis), autoimmune-mediated hypoglycemia, type B insulin resistance with acanthosis nigricans, hypoparathyroidism, Acute immune disorders associated with organ transplantation, chronic immune disorders associated with organ transplantation, osteoarthritis, primary sclerosing cholangitis, idiopathic leukopenia, autoimmune neutropenia, renal disease NOS, glomerulonephritis, microscopic vasculitis of the kidney, discoid lupus, lupus erythematosus, male infertility idiopathic or NOS, sperm autoimmunity, insulin-dependent diabetes mellitus, sympathetic ophthalmia, pulmonary hypertension secondary to connective tissue disease, Goodpasture's syndrome, pulmonary manifestations of polyarteritis nodosa, acute rheumatic fever, rheumatoid spondylitis, Still's disease, systemic Examples of autoimmune diseases include, but are not limited to, sclerosis, Takayasu's disease / arteritis, autoimmune thrombocytopenia, idiopathic thrombocytopenia, autoimmune thyroid disease, hyperthyroidism, goitrous autoimmune hypothyroidism (Hashimoto's disease), atrophic autoimmune hypothyroidism, primary myxedema, suppurative uveitis, primary vasculitis, vitiligo, eosinophilic esophagitis, hypereosinophilic syndrome, eosinophilic gastroenteritis, cutaneous lupus erythematosus, eosinophilic esophagitis, eosinophilic hypereosinophilic syndrome, and eosinophilic gastroenteritis, and diarrhea. In some embodiments, the autoimmune disease is inflammatory bowel disease (IBD). In some embodiments, the autoimmune disease is ulcerative colitis. In some embodiments, the autoimmune disease is Crohn's disease.

[0195] In some embodiments, the compositions provided herein are administered to a subject if the subject has non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), non-alcoholic fatty liver disease (NAFLD), gastroesophageal reflux disease (GERD), or alcoholism.

[0196] In some embodiments, the compositions provided herein are administered to a subject when an immune response associated with bacterial colonization is detected in the subject. In some embodiments, the methods involve determining whether the subject has an immune response induced by or associated with colonization of an undesirable organism.

[0197] In some embodiments, the compositions provided herein are administered to a subject when the subject has dysbiosis (e.g., a microbiota associated with a disease state). In some embodiments, treatment with the compositions provided herein results in a change in the subject's microbiota. In some embodiments, treatment with the compositions provided herein eliminates the dysbiosis in the subject, resulting in a healthy microbiota. In some embodiments, treatment with the compositions provided herein eliminates the dysbiosis in the subject, resulting in a microbiota that is refractory to or less susceptible to infection by pathogens.

[0198] In some embodiments, the compositions and methods described herein are for the treatment and / or prevention of sepsis. In some embodiments, the compositions provided herein are administered to a subject when the subject has sepsis or is at risk of sepsis. In some embodiments, the compositions and methods described herein are for treating and / or preventing sepsis in critically ill patients, such as patients in an intensive care unit (ICU, also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU)). In some embodiments, the compositions provided herein are administered to a subject when the subject is a critically ill subject and has sepsis or is at risk of sepsis. As will be appreciated by those skilled in the art, sepsis is a systemic inflammatory response that typically results from infection with bacteria, fungi, viruses, or protozoa. The severity of sepsis can range from mild (sepsis) to severe sepsis or septic shock. Subjects who are elderly (e.g., over 65 years old), young (e.g., under 1 year old), and / or have an impaired immune system, including those resulting from cancer, diabetes, burns, trauma, or other diseases or disorders that result in serious illness, may be at increased risk of developing sepsis.

[0199] In some embodiments, the compositions and methods described herein are for treating and / or preventing infections in critically ill patients, such as patients in intensive care units (ICUs). In some embodiments, the compositions provided herein are administered to a subject when the subject is a critically ill subject. In some embodiments, the subject may be an intensive care unit patient. In some embodiments, any of the compositions described herein may be administered to a subject to treat and / or prevent bacterial, fungal, viral, or protozoal infections in critically ill subjects.

[0200] In some embodiments, the compositions and methods described herein are for the treatment and / or prevention of infections after a surgical procedure involving the digestive tract (i.e., gastrointestinal surgery). In some embodiments, the compositions and methods described herein are administered to a subject when the subject has undergone a surgical procedure involving the digestive tract. In some embodiments, the compositions and methods described herein are administered to a subject when the subject has undergone a surgical procedure involving the digestive tract (e.g., administered before the surgical procedure). In some embodiments, the subject has a disease or disorder associated with the digestive tract. In some embodiments, any of the compositions described herein may be administered to a subject to treat and / or prevent a bacterial infection, a fungal infection, a viral infection, or a protozoal infection.

[0201] In some embodiments, the compositions and methods described herein are for the treatment and / or prevention of infectious diseases in subjects with cirrhosis (i.e., cirrhotic patients). In some embodiments, the compositions and methods described herein are administered to a subject if the subject has or is at risk for cirrhosis. As will be appreciated by those skilled in the art, cirrhosis, also known as cirrhosis of the liver or cirrhosis of the liver, is a condition associated with impaired liver function, primarily due to long-term damage to liver tissue and its cells. Cirrhosis can be caused by any of a variety of factors, such as hepatitis (e.g., viral infection with hepatitis B or hepatitis C, autoimmune hepatitis) and excessive alcohol consumption. In some embodiments, any of the compositions described herein can be administered to a subject to treat and / or prevent bacterial, fungal, viral, or protozoal infections in cirrhotic patients.

[0202] In some embodiments, the compositions and methods described herein are for the treatment and / or prevention of infection in a subject who has undergone a bone marrow transplant (i.e., a bone marrow transplant patient). In some embodiments, the compositions and methods described herein are administered to a subject if the subject has undergone or will undergo a bone marrow transplant. In some embodiments, any of the compositions described herein may be administered to a subject to treat and / or prevent bacterial, fungal, viral, or protozoal infections in bone marrow transplant patients.

[0203] Any of the compositions described herein may be administered to a subject in a therapeutically effective amount or dose to treat or prevent, for example, a disease or disorder associated with bacterial colonization or an immune response associated with bacterial colonization. The terms "treat" and "treatment" refer to reducing or alleviating one or more symptoms associated with bacterial colonization or an immune response associated with bacterial colonization. In some embodiments, any of the compositions described herein may be administered to a subject to prevent a disease or disorder. In some embodiments, any of the compositions described herein may be administered to a subject to prevent a Th1-related disease or disorder. In some embodiments, any of the compositions described herein may be administered to a subject to prevent IBD. The terms "prevent" and "prevention" encompass prophylactic administration and may reduce the incidence or likelihood of bacterial colonization or an immune response associated with bacterial colonization. For example, in some embodiments, administration of a composition provided herein results in a healthy microbiota that is resistant to pathogenic infection, thereby preventing pathogenic infection or recolonization by pathogenic organisms.

[0204] As used herein, the term "therapeutically effective amount" may be used interchangeably with the term "effective amount." A therapeutically effective amount or effective amount of a composition, such as a pharmaceutical composition, is any amount that results in a desired response or outcome in a subject, such as those described herein, including, but not limited to, reduction or prevention of bacterial colonization or immune responses associated with bacterial colonization.

[0205] It should be understood that the term effective amount may be expressed as the number of bacteria or bacterial spores administered. It should further be understood that bacteria may multiply when administered. Thus, even administering a relatively small amount of bacteria may be therapeutically effective.

[0206] In some embodiments, a therapeutically effective amount of any of the compositions described herein is an amount sufficient to enhance survival of a subject, reduce or prevent bacterial colonization in a subject, and / or reduce or inhibit toxin production by a pathogenic infection. In some embodiments, colonization may be assessed by detecting and / or quantifying bacteria in a sample from the subject, such as a fecal sample. In some embodiments, a therapeutically effective amount is an amount that increases the number of colonizing bacteria (e.g., pathogenic organisms, multidrug-resistant organisms, such as carbapenem-resistant Enterobacteriaceae or extended-spectrum β-lactamase-producing Enterobacteriaceae) in a fecal sample from the 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, 10 ... 4 double, 10 5 The amount is sufficient to reduce the concentration by a factor of 1 or more.

[0207] In some embodiments, the compositions provided herein reduce an immune response associated with or induced by bacterial colonization. In some embodiments, a therapeutically effective amount is an amount sufficient to reduce an immune response associated with or induced by bacterial colonization 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 immune response associated with or induced by bacterial colonization prior to administration of any of the compositions.

[0208] In some embodiments, a therapeutically effective amount is an amount sufficient to recolonize or repopulate the subject's gastrointestinal tract with non-pathogenic bacteria. In some embodiments, a therapeutically effective amount is an amount sufficient to graft one or more of the bacterial strains of the composition into the subject's gastrointestinal tract. In some embodiments, a stool sample is obtained from the subject to assess the bacterial load of undesirable bacteria (e.g., pathogenic organisms, multidrug-resistant organisms, such as carbapenem-resistant Enterobacteriaceae or extended-spectrum β-lactamase-producing Enterobacteriaceae) and / or assess the effectiveness of administration of the bacterial compositions described herein. In some embodiments, the subject's microbiota (e.g., the identity and abundance of strains and / or species of the microbiota) may be assessed to determine the subject's disease state and / or assess the progress of treatment. In some embodiments, the microbiota of a subject with a pathogenic infection is compared to the microbiota of a healthy subject, such as a subject who is not or has never experienced a pathogenic infection. In some embodiments, the microbiota of a subject with a pathogenic infection is compared to the microbiota of the same subject from a fecal sample obtained from the subject prior to the pathogenic infection.

[0209] In some embodiments, administration of a composition provided herein results in a healthy microbiota that reduces or prevents colonization of the subject by any undesirable organisms. In some embodiments, administration of a composition provided herein results in a healthy microbiota that reduces or prevents colonization of the subject's intestine by any undesirable organisms (e.g., pathogenic organisms, multidrug-resistant organisms, such as carbapenem-resistant Enterobacteriaceae or extended-spectrum β-lactamase-producing Enterobacteriaceae). In some embodiments, administration of a composition provided herein results in a healthy microbiota that reduces immune responses associated with bacterial colonization, such as colonization by undesirable bacteria. In some embodiments, administration of a composition provided herein results in a healthy microbiota that reduces Th1 immune responses in the subject.

[0210] Any of the compositions described herein may be administered in combination with one or more additional compositions that may suppress Th1 responses and / or induce the accumulation and / or proliferation of regulatory T cells and / or Th17 cells. In some embodiments, any of the compositions described herein may be administered in combination with a composition that induces the proliferation and / or accumulation of regulatory T cells ("Tregs").

[0211] In some embodiments, any of the compositions described herein may be administered in combination with a Treg-inducing composition of a bacterial strain described, for example, in Atarashi et al., Nature (2013) 500:232-236. In some embodiments, the Treg-inducing composition comprises at least 5, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, or at least 17 of the following species: Clostridium saccharogumia, Flavonifractor plautii, Clostridium hathewayi, Blautia coccoides, Clostridium bolteae ATCC BAA-613, cf. Clostridium sp. MLG055, Clostridium indolis, Anaerotruncus colihominis, Ruminococcus sp. ID8, Clostridium asparagiforme DSM 15981, Clostridium symbiosum, Clostridium ramosum, Eubacterium contortum, Lachnospiraceae bacterium 5_1_57FAA, Lachnospiraceae bacterium 3_1_57FAA_CT1, Clostridiales bacterium 1_7_47FAA, and Lachnospiraceae bacterium A4. It should be understood that subsets of the above bacterial compositions can also induce Treg cells. Examples of subset bacteria that induce Treg cells can be found, for example, in Atarashi et al., Nature (2013) 500:232-236 and corresponding supplementary information. In some embodiments, any of the compositions described herein may be administered in combination with any of the bacterial compositions described in PCT Publication WO 2016 / 209806.

[0212] In some embodiments, any of the compositions described herein may be administered in combination with any of the bacterial compositions described in PCT Publication No. WO 2019 / 094837, which is incorporated herein by reference in its entirety. In some embodiments, any of the compositions described herein may be administered in combination with any of the bacterial compositions described in PCT Publication No. WO 2019 / 118515, which is incorporated herein by reference in its entirety. In some embodiments, any of the compositions described herein is administered in combination with a composition of 36 bacterial strains (e.g., the 36-mix shown in Figure 2).

[0213] As used herein, the phrase "inducing the proliferation and / or accumulation of regulatory T cells" refers to the effect of inducing the differentiation of immature T cells into regulatory T cells, which differentiation results in the proliferation and / or accumulation of regulatory T cells. Furthermore, the meaning of "inducing the proliferation and / or accumulation of regulatory T cells" encompasses in vivo effects, in vitro effects, and / or ex vivo effects. In some embodiments, the proliferation and / or accumulation of regulatory T cells may be assessed by detecting and / or quantifying the number of cells expressing regulatory T cell markers (e.g., Foxp3 and CD4), e.g., by flow cytometry. In some embodiments, the proliferation and / or accumulation of regulatory T cells may be assessed by determining regulatory T cell activity, such as the production of cytokines (e.g., IL-10).

[0214] In some embodiments, any of the compositions described herein may be administered in combination with a composition that induces the accumulation and / or proliferation of Th17 cells, see, e.g., the compositions disclosed in PCT Publication WO 2015 / 156419, which is incorporated by reference in its entirety.

[0215] In some embodiments, suppression of live bacterial products also repopulates the subject's microflora.

[0216] In some embodiments, administration of a composition described herein increases the expansion and / or accumulation of regulatory T cells (e.g., total Tregs or pathogen-specific Tregs) by at least 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 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, 10 ... 4 double, 10 5 In some embodiments, administration of a composition described herein increases the expansion and / or accumulation of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) 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, 10 ... 4 double, 10 5 Increase by a factor of two or more.

[0217] In some embodiments, administration of a composition described herein increases the expansion and / or accumulation of regulatory T cells (e.g., total Tregs or pathogen-specific Tregs) by at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150% or more compared to the amount of regulatory T cells in the subject (or at a particular site in the subject) before administration of the composition. In some embodiments, administration of a composition described herein increases the expansion and / or accumulation of regulatory T cells (e.g., total Tregs or pathogen-specific Tregs) by at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150% or more compared to the amount of regulatory T cells in another subject (e.g., a reference subject) that did not receive the composition.

[0218] The induction of Treg cells and the corresponding decolonization of pathogenic organisms are intricately linked. In some embodiments, administration of a composition described herein increases the expansion and / or accumulation of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by 1% to 20%, 2% to 19%, 3% to 17%, 4% to 16%, 4% to 15%, 5% to 15%, 6% to 14%, 7% to 13%, 8% to 12%, 5% to 10%, 5% to 15%, 10% to 15%, or 8% to 15%, compared to the amount of regulatory T cells in the subject (or a particular site in the subject) before administration of the composition. In some embodiments, administration of a composition described herein increases the proliferation and / or accumulation of regulatory T cells (e.g., total Tregs or pathogen-specific Tregs) by 1% to 20%, 2% to 19%, 3% to 17%, 4% to 16%, 4% to 15%, 5% to 15%, 6% to 14%, 7% to 13%, 8% to 12%, 5% to 10%, 5% to 15%, 10% to 15%, or 8% to 15%, compared to the amount of regulatory T cells in another subject (e.g., a reference subject) that did not receive the composition.

[0219] In some embodiments, administration of a composition described herein results in an increase in the activity of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) at a particular site (e.g., the gastrointestinal tract) of a subject. In some embodiments, administration of a composition described herein increases the activity of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 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, 10 ... 4 double, 10 5In some embodiments, administration of a composition described herein increases the activity of regulatory T cells (e.g., total Tregs or pathogen-specific Tregs) 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, 10 ... 4 double, 10 5 Increase by a factor of two or more.

[0220] In some embodiments, administration of a composition described herein increases the activity of regulatory T cells (e.g., total Tregs or pathogen-specific Tregs) by at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150% or more compared to the activity of regulatory T cells in the subject (or at a particular site in the subject) before administration of the composition. In some embodiments, administration of a composition described herein increases the activity of regulatory T cells (e.g., total Tregs or pathogen-specific Tregs) by at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150% or more compared to the activity of regulatory T cells in another subject (e.g., a reference subject) that did not receive the composition.

[0221] The abundance of regulatory T cells (e.g., total Tregs or pathogen-specific Tregs) can be assessed by any method known in the art, such as by detecting a cellular marker indicative of regulatory T cells (e.g., FoxP3), by assessing the direct or indirect activity of regulatory T cells, and / or by measuring the production of one or more cytokines (e.g., IL-10) produced by regulatory T cells.

[0222] Some aspects of the compositions and methods described herein increase the production of short-chain fatty acids (e.g., in the gastrointestinal tract of a subject). In some embodiments, the methods involve administering to a subject one or more compositions containing a bacterial strain that produces short-chain fatty acids. SCFAs are abundant in healthy subjects (e.g., subjects without a pathogenic organism infection) and are decreased in subjects with a pathogenic organism infection (e.g., Clostridium difficile infection and rCDI). Fecal transplantation (FMT) has been shown to increase SCFAs after rCDI (Seekatz, et al., Anaerobe (2018) 53:64-73).

[0223] SCFAs produced in the gastrointestinal tract are thought to function as signaling molecules between the gut microbiota and the host organism, and SCFAs affect local, intermediary, and peripheral metabolism in the host. See, for example, Morrison, et al., Gut Microbes (2016) 7(3):189-200. In some embodiments, damaged intestinal mucosal barriers can be repaired by providing SCFAs.

[0224] Examples of SCFAs include, but are not limited to, formic acid, acetic acid, butyric acid, isobutyric acid, valeric acid, or isovaleric acid. In some embodiments, the SCFA is butyric acid (butyrate).

[0225] The production of SCFAs and the corresponding decolonization of pathogenic organisms are intricately linked. In some embodiments, administration of a composition described herein increases the production and / or accumulation of SCFAs (e.g., total SCFAs or pathogenic organism-specific SCFAs) by 1% to 20%, 2% to 19%, 3% to 17%, 4% to 16%, 4% to 15%, 5% to 15%, 6% to 14%, 7% to 13%, 8% to 12%, 5% to 10%, 5% to 15%, 10% to 15%, or 8% to 15%, compared to the amount of SCFAs in the subject (or a particular region of the subject) prior to administration of the composition. In some embodiments, administration of a composition described herein increases the production and / or accumulation of SCFAs (e.g., total SCFAs or pathogen-specific SCFAs) by 1% to 20%, 2% to 19%, 3% to 17%, 4% to 16%, 4% to 15%, 5% to 15%, 6% to 14%, 7% to 13%, 8% to 12%, 5% to 10%, 5% to 15%, 10% to 15%, or 8% to 15%, compared to the amount of SCFAs in another subject (e.g., a reference subject) that did not receive the composition.

[0226] In some embodiments, the compositions and methods described herein result in an increase in the amount of SCFAs produced in the digestive tract of a subject. In some embodiments, SCFAs are increased 10-500-fold after administration of a composition described herein. In some embodiments, SCFAs are increased 20-250-fold after administration of a composition described herein. In some embodiments, SCFAs are increased 100-500-fold after administration of a composition described herein. In some embodiments, SCFAs are increased at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold after administration of a composition described herein.

[0227] In some embodiments, the SCFA comprises butyrate. In some embodiments, butyrate levels (e.g., in the gastrointestinal tract of a subject) are increased 10-fold to 500-fold after administration of a composition described herein. In some embodiments, butyrate levels are increased 20-fold to 250-fold after administration of a composition described herein. In some embodiments, butyrate levels are increased 100-fold to 500-fold after administration of a composition described herein. In some embodiments, butyrate levels are increased at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold after administration of a composition described herein.

[0228] In some embodiments, the SCFA comprises propionate. In some embodiments, propionate levels (e.g., in the gastrointestinal tract of a subject) are increased 10-fold to 500-fold after administration of a composition described herein. In some embodiments, propionate levels are increased 20-fold to 250-fold after administration of a composition described herein. In some embodiments, propionate levels are increased 100-fold to 500-fold after administration of a composition described herein. In some embodiments, propionate levels are increased at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold after administration of a composition described herein.

[0229] In some embodiments, the SCFA comprises acetate. In some embodiments, acetate levels (e.g., in the gastrointestinal tract of a subject) are increased 10-fold to 500-fold after administration of a composition described herein. In some embodiments, acetate levels are increased 20-fold to 250-fold after administration of a composition described herein. In some embodiments, acetate levels are increased 100-fold to 500-fold after administration of a composition described herein. In some embodiments, acetate levels are increased at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold after administration of a composition described herein.

[0230] In some embodiments, the SCFA comprises formate. In some embodiments, acetate levels (e.g., in the gastrointestinal tract of a subject) are increased 10- to 500-fold after administration of a composition described herein. In some embodiments, formate levels are increased 20- to 250-fold after administration of a composition described herein. In some embodiments, formate levels are increased 100- to 500-fold after administration of a composition described herein. In some embodiments, formate levels are increased at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold after administration of a composition described herein.

[0231] In some embodiments, the subject is infected with a pathogenic organism. In some embodiments, the subject has Clostridium difficile infection (CDI). In some embodiments, the CDI is recurrent (rCDI). rCDI is CDI that occurs multiple times in the same subject and is associated with a decrease in short-chain fatty acids (SCFAs), an increase in primary bile acids, and a decrease in secondary bile acids in the subject's gut microbiota.

[0232] Bile acids are steroid acids that act as surfactants, converting fats and oils into micelles, thereby enabling the digestion of dietary fats and oils. Bile acids also act as hormones that utilize the farnesoid X receptor and GBPAR1. Primary bile acids are synthesized in the liver from cholesterol and are conjugated with either taurine or glycine before secretion. Once primary bile acids are secreted into the intestinal lumen, bacteria partially dehydroxylate them, removing the glycine or taurine group to form secondary bile acids.

[0233] Non-limiting examples of primary bile acids are cholic acid (CA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and tulochenodeoxycholic acid (TCDCA). Non-limiting examples of secondary bile acids are deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), taurodeoxycholic acid (TDCA), taurolithocholic acid (TLCA), and tauroursodeoxycholic acid (TUDCA).

[0234] Pathogenic organism infections, including Clostridium difficile infection and rCDI, are associated with an increase in primary bile acids and a decrease in secondary bile acids. Primary bile acids decrease, and secondary bile acids increase after fecal transplantation (FMT) (Seekatz, et al., Anaerobe (2018) 53:64-73). In some embodiments, administration of a bacterial strain or pharmaceutical composition described herein reduces primary bile acids and / or increases secondary bile acids.

[0235] In some embodiments, the level of a primary bile acid is reduced 10-fold to 100,000-fold after administration of the bacterial strain or pharmaceutical composition. In some embodiments, the level of a primary bile acid is reduced 10-fold to 1,000-fold after administration of the bacterial strain or pharmaceutical composition. In some embodiments, the level of a primary bile acid is reduced 20-fold to 10,000-fold after administration of the bacterial strain or pharmaceutical composition. In some embodiments, the level of the primary bile acid is reduced 10-fold, 100-fold, 200-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 800-fold, 900-fold, 1,000-fold, 10,000-fold, 20,000-fold, 30,000-fold, 40,000-fold, 50,000-fold, 60,000-fold, 70,000-fold, 80,000-fold, 90,000-fold, or 100,000-fold after administration of the bacterial strain or pharmaceutical composition.

[0236] In some embodiments, the level of secondary bile salts is increased 10-fold to 10,000-fold after administration of the bacterial strain or pharmaceutical composition. In some embodiments, the level of secondary bile acids is increased 10-fold to 1,000-fold after administration of the bacterial strain or pharmaceutical composition. In some embodiments, the level of secondary bile acids is increased 20-fold to 100-fold after administration of the bacterial strain or pharmaceutical composition. In some embodiments, the level of secondary bile acids is increased 10-fold, 20-fold, 50-fold, 100-fold, 200-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 800-fold, 900-fold, 1,000-fold, 2,000-fold, 3,000-fold, 4,000-fold, 5,000-fold, 6,000-fold, 7,000-fold, 8,000-fold, 9,000-fold, or 1,000-fold after administration of the bacterial strain or pharmaceutical composition.

[0237] Generally, short-chain fatty acids (SCFAs) are fatty acids containing six or fewer carbon atoms. SCFAs are produced when dietary fiber is fermented in the intestine. Non-limiting examples of SCFAs include hexanoate, pentanoate, butyrate, propionate, acetate, and formate. SCFAs are primarily absorbed into the portal vein after lipid digestion and can affect the production of lipids, energy, and vitamins. Furthermore, SCFAs play an important role in maintaining the integrity of intestinal epithelial cell membranes to prevent infection by pathogenic organisms (e.g., Clostridium difficile).

[0238] In one aspect, the present disclosure provides a method comprising multiple doses of a pharmaceutical composition. In some embodiments, the present disclosure provides a method comprising administration of an antibiotic (e.g., vancomycin) followed by multiple doses of a pharmaceutical composition. In some embodiments, administration of multiple doses of a pharmaceutical composition described herein provides enhanced colonization (engraftment) of one or more bacterial strains of the pharmaceutical composition compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of a pharmaceutical composition described herein provides enhanced recovery of one or more bacterial strains of the pharmaceutical composition compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of a pharmaceutical composition described herein provides increased abundance of one or more bacterial strains of the pharmaceutical composition compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of a pharmaceutical composition described herein provides increased abundance of one or more bacterial strains of the pharmaceutical composition compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides persistent colonization (e.g., up to 6 months) of one or more bacterial strains of the pharmaceutical composition compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides persistent colonization (e.g., up to 6 months) of all bacterial strains of the pharmaceutical composition compared to administration of a single dose of the pharmaceutical composition. It should further be understood that administration of multiple doses may result in a combination of the described results. Thus, for example, in some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides enhanced colonization (engraftment) and increased recovery rates of one or more bacterial strains of the pharmaceutical composition compared to administration of a single dose of the pharmaceutical composition.

[0239] In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides enhanced colonization (engraftment) of one or more bacterial strains of the pharmaceutical composition compared to administration of a single dose of the pharmaceutical composition. Multiple doses of the pharmaceutical composition may result in enhanced colonization (engraftment) and increased abundance of each bacterial strain of the pharmaceutical composition. In some embodiments, administration of a single dose of the pharmaceutical composition results in the same or similar level of engraftment (e.g., total bacteria) as administration of multiple doses of the pharmaceutical composition, but engraftment may be dominated by only one bacterial strain or a subset of bacterial strains of the pharmaceutical composition.

[0240] Any of the methods described herein may involve administering an antibiotic to the subject prior to administration of a pharmaceutical composition described herein. In some embodiments, the antibiotic is vancomycin, fidaxomicin, or ridinilazole. Non-limiting examples of antibiotics that may be used in any of the methods provided herein include the cephalosporin antibiotics cephalexin, cefuroxime, cefadroxil, cefazolin, cephalothin, cefaclor, cefamandole, cefoxitin, cefprozil, ceftobiprole, clindamycin, ceftriaxone, cefotaxime, cefazolin, cefoperazone, cefuroxime, cefmetazole, fluoroquinolones, ciprofloxacin, Levaquin, Floxacin, Tequin, Avelox, and Norfloxacin. These include cyclosporine, tetracycline, minocycline, oxytetracycline, doxycycline, amoxicillin, ampicillin, penicillin V, dicloxacillin, benzylpenicillin, carbenicillin, vancomycin and methicillin, ertapenem, doripenem, imipenem / cilastatin, meropenem, clavulanate, tazobactam, piperacillin, ceftriaxone, cefotaxime, cefazolin, fluoroquinolones, imipenem, meropenem, metronidazole, fidaxomixin, or ridinilazole.

[0241] In some embodiments, any of the methods described herein may further include administering vancomycin to the subject prior to administration of a pharmaceutical composition described herein. In some embodiments, the methods do not include administering an antibiotic to the subject prior to administration of a pharmaceutical composition described herein. In some embodiments, the methods do not include administering vancomycin to the subject prior to administration of a pharmaceutical composition described herein. Vancomycin administration has been found to alter the composition of the human gut microbiota. See, for example, Reijnders et al. Cell Metabolism (2016) 24(1):63-72. Without wishing to be bound by any particular theory, it is believed that administration of vancomycin may aid in the engraftment of the bacterial strain(s) of the pharmaceutical compositions described herein, for example, by eliminating other microorganisms present in the digestive tract.

[0242] In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject once as a single dose. In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject in multiple doses. In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject in at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. Multiple doses of the antibiotic (e.g., vancomycin) may be administered to the subject at regular intervals prior to administering any of the pharmaceutical compositions described herein. In some embodiments, each of the multiple doses of the antibiotic (e.g., vancomycin) is administered on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.). In some embodiments, an antibiotic (e.g., vancomycin) is administered to a subject for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more consecutive days. In some embodiments, an antibiotic (e.g., vancomycin) is administered to a subject daily for 3 consecutive days. In some embodiments, an antibiotic (e.g., vancomycin) is administered to a subject daily for 5 consecutive days. In some embodiments, an antibiotic (e.g., vancomycin) is administered to a subject daily for 7 consecutive days. In some embodiments, an antibiotic (e.g., vancomycin) is administered to a subject for 1 day. In any of the embodiments described herein, a subject may be administered one or more doses of a first antibiotic, followed by one or more doses of a second antibiotic.

[0243] In some embodiments, the single dose or the first dose of a multiple dose treatment regimen is administered on the same day as the administration of the final dose of antibiotic (e.g., vancomycin). In some embodiments, the single dose or the first dose of a multiple dose treatment regimen is administered the day after the administration of the final dose of antibiotic (e.g., vancomycin). In some embodiments, the single dose or the first dose of a multiple dose treatment regimen is administered two days after the administration of the final dose of antibiotic (e.g., vancomycin). In some embodiments, the methods provided herein allow for a drug holiday between the final dose of antibiotic (e.g., vancomycin) and the first dose of the pharmaceutical composition. In some embodiments, the single dose or the first dose of a multiple dose treatment regimen is administered 3, 4, 5, 6, 10, or more days after the administration of the final dose of antibiotic (e.g., vancomycin). In some embodiments, the methods provided herein allow for multiple drug holidays between the final dose of antibiotic (e.g., vancomycin) and the first dose of the pharmaceutical composition.

[0244] Each dose of antibiotic (e.g., vancomycin) can be the same amount of antibiotic or can be a different amount of antibiotic. In some embodiments, the antibiotic (e.g., vancomycin) is administered in an amount sufficient to allow colonization of one or more bacterial strains of the pharmaceutical compositions described herein. In some embodiments, a subject is administered about 50 mg to 1 g, 100 mg to 750 mg, 100 mg to 500 mg, 200 mg to 750 mg, 200 mg to 500 mg, 300 mg to 750 mg, 300 mg to 500 mg, 100 mg to 400 mg, 100 mg to 300 mg, 100 mg to 200 mg, 200 mg to 400 mg, 200 mg to 300 mg, or 450 mg to 550 mg of antibiotic per day. As will be appreciated by those skilled in the art, the total amount of vancomycin administered to a subject per day can be administered in a single dose or multiple doses, totaling the total daily amount of antibiotic.

[0245] In some examples, the subject is administered about 500 mg / day of vancomycin prior to administration of any of the pharmaceutical compositions described herein. In some embodiments, 500 mg of vancomycin per day is administered in a single dose (e.g., 500 mg). In some embodiments, 500 mg of vancomycin per day is administered in multiple doses (e.g., 2, 3, 4, 5 or more) resulting in 500 mg of vancomycin per day. In some embodiments, 500 mg of vancomycin is administered in four doses of 125 mg of vancomycin per day. In some embodiments, 500 mg of vancomycin is administered to a subject daily. In some embodiments, 500 mg of vancomycin is administered to a subject daily for two days. In some embodiments, 500 mg of vancomycin is administered to a subject daily for three days. In some embodiments, 500 mg of vancomycin is administered to a subject daily for four days. In some embodiments, 500 mg of vancomycin is administered to a subject per day for 5 days. In some embodiments, 500 mg of vancomycin is administered to a subject per day for 6 days. In some embodiments, 500 mg of vancomycin is administered to a subject per day for 7 days. In some embodiments, 500 mg of vancomycin is administered to a subject per day for 8 days. In some embodiments, 500 mg of vancomycin is administered to a subject per day for 9 days. In some embodiments, 500 mg of vancomycin is administered to a subject per day for 10 days.

[0246] In some embodiments, the subject is administered about 250 mg of vancomycin per day prior to administration of any pharmaceutical composition described herein. In some embodiments, the 250 mg of vancomycin per day is administered in a single dose (e.g., 250 mg). In some embodiments, the 250 mg of vancomycin per day is administered in multiple doses (e.g., 2, 3, 4, 5 or more), resulting in 250 mg of vancomycin per day. In some embodiments, the 250 mg of vancomycin is administered in two doses of 125 mg of vancomycin per day. In some embodiments, 250 mg of vancomycin is administered to a subject daily. In some embodiments, 250 mg of vancomycin is administered to a subject daily for two days. In some embodiments, 250 mg of vancomycin is administered to a subject daily for three days. In some embodiments, 250 mg of vancomycin is administered to a subject daily for four days. In some embodiments, 250 mg of vancomycin is administered to a subject per day for 5 days. In some embodiments, 250 mg of vancomycin is administered to a subject per day for 6 days. In some embodiments, 250 mg of vancomycin is administered to a subject per day for 7 days. In some embodiments, 250 mg of vancomycin is administered to a subject per day for 8 days. In some embodiments, 250 mg of vancomycin is administered to a subject per day for 9 days. In some embodiments, 250 mg of vancomycin is administered to a subject per day for 10 days.

[0247] In some embodiments, the subject is administered about 125 mg of vancomycin per day prior to administration of any pharmaceutical composition described herein. In some embodiments, the 125 mg of vancomycin per day is administered in a single dose (e.g., 125 mg). In some embodiments, the 125 mg of vancomycin per day is administered in multiple doses (e.g., 2, 3, 4, 5 or more), resulting in 125 mg of vancomycin per day. In some embodiments, 125 mg of vancomycin is administered to a subject per day. In some embodiments, 125 mg of vancomycin is administered to a subject per day for two days. In some embodiments, 125 mg of vancomycin is administered to a subject per day for three days. In some embodiments, 125 mg of vancomycin is administered to a subject per day for four days. In some embodiments, 125 mg of vancomycin is administered to a subject per day for five days. In some embodiments, 125 mg of vancomycin is administered to a subject per day for six days. In some embodiments, 125 mg of vancomycin is administered to a subject daily for 7 days. In some embodiments, 125 mg of vancomycin is administered to a subject daily for 8 days. In some embodiments, 125 mg of vancomycin is administered to a subject daily for 9 days. In some embodiments, 125 mg of vancomycin is administered to a subject daily for 10 days.

[0248] In some embodiments, the present disclosure provides methods comprising administering one or more antibiotics to a subject, followed by administering any of the bacterial compositions to the subject one, two, three, four, five, six, seven, eight, nine, or at least ten or more times. In some embodiments, the present disclosure provides methods comprising administering one or more antibiotics to a subject, followed by administering any of the bacterial compositions described herein to the subject in multiple doses at regular intervals, such as every two weeks, one month, two months, three months, four months, five months, six months, or more. In some embodiments, one dose of any of the compositions described herein is administered, and a second dose of the composition is administered the following day (e.g., on consecutive days). In some embodiments, one dose of any of the compositions described herein is administered, and each additional dose of the composition is administered on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.).

[0249] In one aspect, the disclosure provides a method comprising administering one or more antibiotics to a subject, followed by administration of any bacterial composition as multiple daily doses of a pharmaceutical composition. In some embodiments, the pharmaceutical composition is administered daily for 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or more.

[0250] In some embodiments, the antibiotic (e.g., vancomycin) is administered according to a pulse tapered regime. See, e.g., Sirbu et al., Clinical Infectious Diseases (2017) 65:1396-1399.

[0251] In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject at least 1, 2, 3, 4, 5, 6, 7, or more days prior to administration of the pharmaceutical compositions described herein. In some embodiments, administration of the antibiotic (e.g., vancomycin) is terminated at least 1 day (e.g., 1, 2, 3, 4, 5, or more) prior to administration of any of the pharmaceutical compositions described herein.

[0252] In some embodiments, an additional antibiotic is administered in combination with the vancomycin regimen provided herein.

[0253] It is understood that in some embodiments, any dose or administration regimen of vancomycin may be combined with any dose or administration regimen of the pharmaceutical compositions provided herein.

[0254] In one aspect, the present disclosure provides a method comprising administering an antibiotic (e.g., vancomycin) followed by administration of a pharmaceutical composition provided herein, wherein the administration of the antibiotic (e.g., vancomycin) is followed by administration of a single dose or multiple doses of the pharmaceutical composition. In some embodiments, the administration of the antibiotic (e.g., vancomycin) followed by administration of a single dose or multiple doses of the pharmaceutical composition results in increased abundance (engraftment) of the bacterial strain of the pharmaceutical composition in the microbiota of the subject compared to administration of the pharmaceutical composition without the antibiotic. In some embodiments, the administration of the antibiotic (e.g., vancomycin) followed by administration of a single dose or multiple doses of the pharmaceutical composition results in an increased duration of colonization of the bacterial strain of the pharmaceutical composition in the microbiota of the subject (e.g., up to 6 months) compared to administration of the pharmaceutical composition without the antibiotic.

[0255] In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by administration of a single dose or multiple doses of the pharmaceutical composition results in a 10- to 100-fold increase (e.g., within the first 48 hours) in the engraftment rate of the initial amount of bacterial strain of the pharmaceutical composition in the subject's microbiome, compared to administration of the pharmaceutical composition without administration of the antibiotic.

[0256] In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by administration of a single dose or multiple doses of the pharmaceutical composition results in a greater number (amount) of subjects in whose microbiome all bacterial strains of the pharmaceutical composition are present compared to administration of the pharmaceutical composition without administration of the antibiotic.

[0257] In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by multiple doses of the pharmaceutical composition results in increased abundance (engraftment) of the bacterial strain of the pharmaceutical composition in the subject's microbiota compared to administration of a single dose of the pharmaceutical composition. In some embodiments, the disclosure provides a method comprising administering a pharmaceutical composition provided herein, wherein administration of multiple doses of the pharmaceutical composition increases abundance (engraftment) of the bacterial strain of the subject's microbiota of the pharmaceutical composition in the subject's microbiota compared to administration of a single dose of the pharmaceutical composition.

[0258] In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by multiple doses of the pharmaceutical composition results in an increased engraftment rate of the initial amount of bacterial strain of the pharmaceutical composition in the microbiota of the subject compared to administration of a single dose of the pharmaceutical composition. In some embodiments, the disclosure provides a method comprising administering a pharmaceutical composition provided herein, wherein administration of multiple doses of the pharmaceutical composition increases the engraftment rate of the initial amount of bacterial strain of the pharmaceutical composition in the microbiota of the subject compared to administration of a single dose of the pharmaceutical composition.

[0259] In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by multiple doses of the pharmaceutical composition results in a higher abundance of the bacterial strain of the pharmaceutical composition in the subject's microbiome compared to administration of a single dose of the pharmaceutical composition. In some embodiments, the present disclosure provides a method comprising administering a pharmaceutical composition provided herein, wherein administration of multiple doses of the pharmaceutical composition results in a higher abundance of the bacterial strain of the pharmaceutical composition in the subject's microbiome compared to administration of a single dose of the pharmaceutical composition.

[0260] In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by multiple doses of the pharmaceutical composition results in a greater number of subjects having all of the bacterial strains of the pharmaceutical composition present in their microbiota compared to administration of a single dose of the pharmaceutical composition. In some embodiments, the present disclosure provides methods comprising administration of a pharmaceutical composition provided herein, wherein administration of multiple doses of the pharmaceutical composition results in a greater number of subjects having all of the bacterial strains of the pharmaceutical composition in their microbiota compared to administration of a single dose of the pharmaceutical composition.

[0261] In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by multiple doses of the pharmaceutical composition results in accelerated recovery of the microbiota (e.g., an increase in bacterial species of Bacteroidetes and / or Firmicutes and / or a decrease in Proteobacteria) compared to administration of a single dose of the pharmaceutical composition. In some embodiments, the disclosure provides methods comprising administration of a pharmaceutical composition provided herein, wherein administration of multiple doses of the pharmaceutical results in accelerated recovery of the microbiota (e.g., an increase in bacterial species of Bacteroidetes and / or Firmicutes and / or a decrease in Proteobacteria) compared to administration of a single dose of the pharmaceutical composition.

[0262] In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by administration of a single dose or multiple doses of the pharmaceutical composition results in accelerated recovery of the microbiota (e.g., an increase in bacterial species of Bacteroidetes and / or Firmicutes, and / or a decrease in Proteobacteria) compared to administration of the antibiotic (e.g., vancomycin) without administration of the pharmaceutical composition.

[0263] In some embodiments, any of the methods described herein may further include administering to a subject a composition comprising taurine. In some embodiments, the composition comprising taurine is administered simultaneously with any pharmaceutical composition comprising the purified bacterial mixture described herein. In some embodiments, the composition comprising taurine is administered before administration of any pharmaceutical composition comprising the purified bacterial mixture described herein. In some embodiments, the composition comprising taurine is administered after administration of any pharmaceutical composition comprising the purified bacterial mixture described herein. In some embodiments, the composition comprising taurine is administered before and after administration of any pharmaceutical composition comprising the purified bacterial mixture described herein.

[0264] Taurine, also known as 2-aminoethanesulfonic acid, is an organic compound widely distributed in animal tissues, is a major component of bile, and can be found conjugated to bile acids. Taurine can account for up to 0.1% of a person's total body weight and can be found in the large intestine, among other locations. The exact function of taurine in physiological processes is unknown, but without wishing to be bound by any particular theory, it is thought that taurine may help support muscle maintenance.

[0265] Taurine is naturally found in fish and meat, and human consumption generally ranges between 40 mg and 400 mg per day. However, in recent years, taurine has been included in nutritional drinks for human consumption. One example of an energy drink sold under the trademark Red Bull® contains approximately 1000 mg of taurine per can (serving). High taurine consumption is generally considered safe, with no adverse effects observed from up to 3000 mg of taurine per day.

[0266] Taurine administration has been found to alter the composition of the mouse gut microbiota. It has recently been reported that infection can induce host taurine production and the proliferation of taurine-utilizing bacteria. When bile acids are released into the intestine from the gallbladder, intestinal bacteria can cleave taurine from the bile acids, making it available for use as an energy source. For example, bacteria of the class Deltaproteobacteria, such as Biophila wadsworthia, utilize taurine in anaerobic respiration, and the proliferation of Deltaproteobacteria after taurine administration is thought to help inhibit intestinal colonization by Klebsiella pneumoniae and Citrobacter rodentium, mouse models of pathogenic E. coli. For an example, see Stacy et al. Cell. 2021 184(3):615-627.

[0267] As a result, gut microbiota from previously infected hosts have been found to exhibit enhanced resistance to infection. Microbiota from previously infected hosts are associated with altered bile acid metabolism, resulting in an expansion of taxa that utilize the sulfonic acid, taurine. In fact, it has been reported that supplying exogenous taurine alone is sufficient to induce this change in microbiota function and enhance resistance. Mechanistically, taurine enhances microbiota production of sulfide, an inhibitor of cellular respiration that is key to host invasion by many pathogens. See, for example, Stacy et al. Cell. 2021 184(3):615-627.

[0268] Without wishing to be bound by any particular theory, it is believed that administration of taurine may promote replication and / or aid in engraftment of the bacterial strain(s) of the pharmaceutical compositions described herein, for example, by serving as an energy source for bacteria present in the gastrointestinal tract or in the pharmaceutical compositions.

[0269] In some embodiments, Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, BilophilaA composition comprising at least two strains selected from the group consisting of Bacillus wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri, in combination with taurine, may be more effective at inhibiting infection and / or reducing / preventing colonization by more pathogens than the addition of taurine alone or the bacterial composition alone.

[0270] As described herein, any of the bacterial compositions may further comprise taurine. In such embodiments, the bacterial strain and taurine are administered to the subject simultaneously. In some embodiments, the taurine is administered to the subject in a separate composition, such as a pharmaceutical composition or food product, including a beverage product.

[0271] In some embodiments, the composition comprises about 40 mg to about 3000 mg of taurine, in some embodiments, about 100 mg to about 2000 mg of taurine, in some embodiments, about 500 mg to about 1500 mg of taurine.

[0272] In some embodiments, the composition comprising the bacterial strain also comprises taurine. In some embodiments, the composition comprises about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg , 950mg, 1000mg, 1100mg, 1200mg, 1300mg, 1400mg, 1500mg, 1600mg, 1700mg, 1800mg, 1900mg, 2000mg, 2100mg, 2200mg, 2300mg, 2400mg, 2500mg, 2600mg, 2700mg, 2800mg, 2900mg, or 3000mg of taurine.

[0273] In some embodiments, a subject is administered about 40 mg to about 3000 mg of taurine per day. In some embodiments, a subject is administered about 100 mg to about 2000 mg of taurine per day. In some embodiments, a subject is administered about 500 mg to about 1500 mg of taurine per day. Any daily amount of taurine may be administered to a subject as a single dose or multiple doses throughout the day.

[0274] In some embodiments, the composition comprising taurine is administered to the subject once as a single dose. In some embodiments, the composition comprising taurine is administered to the subject in multiple doses. In some embodiments, the composition comprising taurine is administered to the subject in at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses.

[0275] One or more doses of a composition comprising taurine may be administered to a subject prior to administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered multiple times, such as on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.) prior to administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered to a subject for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more consecutive days prior to administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered to a subject for each of three consecutive days prior to administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered to a subject for each of five consecutive days prior to administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, a composition comprising taurine is administered to a subject for seven consecutive days before administering any pharmaceutical composition containing the purified bacterial strain described herein.In some embodiments, a composition comprising taurine is administered to a subject one day before administering any pharmaceutical composition containing the purified bacterial strain described herein.

[0276] One or more doses of a composition comprising taurine may be administered to a subject after administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered multiple times, such as on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.) after administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered to a subject for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more consecutive days after administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered to a subject for each of three consecutive days after administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered to a subject for each of five consecutive days after administering any pharmaceutical composition containing a purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered to the subject on each of seven consecutive days after administering any pharmaceutical composition containing the purified bacterial strain described herein.In some embodiments, the composition comprising taurine is administered to the subject on one day after administering any pharmaceutical composition containing the purified bacterial strain described herein.

[0277] In some embodiments, the composition comprising taurine is administered on the same day as any pharmaceutical composition containing the purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered contemporaneously (simultaneously) or substantially contemporaneously with any pharmaceutical composition containing the purified bacterial strain described herein. In some embodiments, the composition comprising taurine is administered within 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, or 18 hours of administration of any pharmaceutical composition containing the purified bacterial strain described herein.

[0278] The composition comprising taurine may be in any form for human administration, such as a food / drink, capsule, pill, tablet, or liquid composition.

[0279] In some embodiments, the methods described herein may involve subjecting the subject to a bowel lavage (bowel irrigation, whole bowel irrigation, gastrointestinal lavage, gastric lavage) prior to administration of the compositions described herein. In some embodiments, the bowel lavage may remove or help remove microflora from the subject's digestive tract, creating a niche for the bacterial strains of the compositions described herein. In some embodiments, the bowel lavage may be an oral or rectal bowel lavage.

[0280] Methods for performing bowel cleansing are known in the art and generally involve the rapid administration of large volumes of a solution, such as polyethylene glycol or a balanced electrolyte solution. Rectal bowel cleansing may involve the administration of a solution or suppository containing a pharmaceutical composition. Bowel cleansing may be performed under medical supervision, in a hospital setting, or at home.

[0281] Any of the compositions described herein, including pharmaceutical compositions and food products containing compositions, may contain bacterial strains embedded in any form, for example, an aqueous form such as a solution or suspension, a semi-solid form, a powder form, or a lyophilized form. In some embodiments, the composition or the bacterial strains in the composition are lyophilized. In some embodiments, a subset of the bacterial strains in the composition is lyophilized. Methods for lyophilizing compositions, particularly compositions containing bacteria, are well known in the art. See, for example, U.S. Pat. No. 3,261,761; U.S. Pat. No. 4,205,132; WO 2014 / 029578; and WO 2012 / 098358, which are incorporated herein by reference in their entireties. Bacteria may be lyophilized as a combination, and / or the bacteria may be lyophilized separately and combined prior to administration. Bacterial strains may be combined with a pharmaceutical excipient before being combined with other bacterial strains, or multiple lyophilized bacteria may be combined in lyophilized form, and the mixture of bacteria may be combined with a pharmaceutical excipient after combination. In some embodiments, the bacterial strain is a lyophilized cake. In some embodiments, the composition comprising one or more bacterial strains is a lyophilized cake.

[0282] In some embodiments, one or more of the bacterial strains of compositions, including pharmaceutical compositions and food products, are spray-dried. In some embodiments, a subset of the bacterial strains are spray-dried. The process of spray-drying refers to the production of a dry powder from a liquid containing the bacterial composition (see, e.g., Ledet, et al., Spray Draying of Pharmaceuticals in "Lyophilized Biologics and Vaccines," pages 273-294, Springer). Generally, the process involves rapidly drying the bacterial composition with hot gas. The bacterial strain may be combined with a pharmaceutical excipient before being combined with other bacterial strains, or multiple spray-dried bacterial strains may be combined in spray-dried form, and the mixture of bacterial strains may be combined and then combined with a pharmaceutical excipient.

[0283] The bacterial strains of the compositions may be produced using fermentation techniques well known in the art. In some embodiments, the active ingredients are produced using anaerobic fermentors, which can support the rapid growth of anaerobic bacterial species. Anaerobic fermentors may be, for example, stirred tank reactors or disposable wave bioreactors. Culture media such as BL medium and EG medium, or similar animal-component-free versions of these media, may be used to support the growth of the bacterial species. The bacterial product may be purified and concentrated from the fermentation broth by traditional techniques such as centrifugation and filtration, and optionally dried and lyophilized by techniques well known in the art.

[0284] In some embodiments, the composition of bacterial 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, such as any two or more purified bacterial strains described herein, with one or more inactive ingredients, which may include one or more pharmaceutically acceptable excipients.

[0285] 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 embodiments, pharmaceutically acceptable excipients are selected based on the intended route of administration of the composition; for example, a composition for oral or nasal administration may contain different pharmaceutically acceptable excipients than a composition for rectal administration. Examples of excipients include sterile water, saline, solvents, bases, emulsifiers, suspending agents, surfactants, stabilizers, flavoring agents, fragrances, excipients, vehicles, preservatives, binders, diluents, isotonicity agents, soothing agents, fillers, disintegrants, buffers, coating agents, lubricants, coloring agents, sweeteners, thickeners, and solubilizers.

[0286] The pharmaceutical compositions disclosed herein can be prepared according to methods well known and routinely practiced 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 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 orally, nasally, or parenterally in the form of, for example, capsules, tablets, pills, sachets, liquids, powders, granules, fine granules, film-coated formulations, pellets, lozenges, sublingual formulations, chewable formulations, buccal formulations, pastes, syrups, suspensions, elixirs, emulsions, liniments, ointments, salves, poultices, transdermal systems, lotions, inhalants, aerosols, injections, suppositories, etc. In some embodiments, the pharmaceutical compositions may be used by injection, such as intravenous, intramuscular, subcutaneous, or intradermal administration.

[0287] Aspects of the present disclosure relate to the administration of a composition comprising taurine. In some embodiments, a composition comprising any of the purified bacterial strains described herein may further comprise taurine. In such embodiments, administering the composition results in the administration of both the purified bacterial strain and taurine to the subject. In some embodiments, a composition comprising any of the purified bacterial strains described herein does not contain taurine. In some embodiments, a composition that is not a composition comprising a purified bacterial strain comprises taurine. In some embodiments, a method involves administering a composition comprising a purified bacterial strain to a subject and administering a second composition comprising taurine to the subject.

[0288] In some embodiments, the composition comprising the bacterial strain is formulated for delivery to the intestine (e.g., the small intestine and / or colon). In some embodiments, the composition comprising the bacterial strain is formulated with an enteric coating, which increases the survival of the bacteria through the harsh environment of the stomach. An enteric coating is a coating that resists the action of gastric fluids in the stomach, allowing the bacteria of the composition in the stomach to pass through the stomach and enter the intestine. The enteric coating may readily dissolve upon contact with intestinal fluids, resulting in the release of the bacteria encapsulated in the coating into the intestinal tract. The enteric coating may be composed 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).

[0289] Compositions containing bacterial strains may also be formulated for rectal delivery to the intestine (e.g., the colon). Thus, in some embodiments, compositions containing bacterial strains may be formulated for delivery via suppository, colonoscopy, endoscopy, sigmoidoscopy, or enema. Pharmaceutical formulations or preparations, particularly those for oral administration, may include additional components that enable efficient delivery of the compositions of the present disclosure to the intestine (e.g., the colon). Various pharmaceutical formulations that enable delivery of the composition to the intestine (e.g., the colon) may be used. Examples include pH-sensitive compositions, more specifically, buffered sachet formulations 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 a pharmaceutical preparation, the pH-sensitive composition is preferably a polymer with a pH threshold of about 6.8 to about 7.5 for degradation of the composition. This range is suitable for delivery to the colon because the pH at the distal end of the stomach shifts to the alkaline side. It should be further understood that each part of the intestine (e.g., the duodenum, jejunum, ileum, cecum, colon, and rectum) has a different biochemical and chemical environment. For example, parts of the intestine have different pHs, allowing for targeted delivery by compositions with specific pH sensitivity. Therefore, the compositions provided herein can be formulated for delivery to the intestine or specific parts of the intestine (e.g., the duodenum, jejunum, ileum, cecum, colon, and rectum) by providing a formulation with appropriate pH sensitivity. (See, e.g., Villena et al., Int J Pharm (2015) 487(1-2):314-9).

[0290] Another embodiment of a pharmaceutical formulation useful for delivering a composition to the intestine (e.g., the colon) ensures delivery to the colon by delaying the release of the contents (e.g., a bacterial strain) for approximately 3 to 5 hours, corresponding to the small intestinal transit time. In one embodiment of a pharmaceutical formulation for delayed release, a hydrogel is used as the shell. The hydrogel hydrates and swells upon contact with gastrointestinal fluids, resulting in effective release of the contents (primarily in the colon). Delayed-release dosage units include drug-containing compositions having a material that coats or selectively coats the administered drug or active ingredient. Examples of such selective coating materials include in vivo degradable polymers, gradually hydrolyzable polymers, gradually water-soluble polymers, and / or enzymatically degradable polymers. A wide variety of coating materials are available for efficiently delaying release, including, for example, cellulose-based polymers such as hydroxypropyl cellulose, acrylic polymers and copolymers such as methacrylic acid polymers and copolymers, and vinyl polymers and copolymers such as polyvinylpyrrolidone.

[0291] Further examples of pharmaceutical compositions that allow for delivery to the intestine (e.g., the 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, particularly in the gastrointestinal tract, from degradation due to protease activity.

[0292] Another example of a system that enables delivery to the intestine (e.g., the colon) is a system that delivers a composition to the colon by pressure changes, such that the contents are released by utilizing the pressure changes caused by gas generation during bacterial fermentation in the distal part of the stomach. More specifically, such a system is, but is not limited to, a capsule in which the contents are dispersed in a suppository base and coated with a hydrophobic polymer (e.g., ethyl cellulose).

[0293] Further examples of systems that allow delivery of compositions to the intestine (e.g., the colon) include compositions that include a coating that can be removed by enzymes present in the intestine (e.g., the colon), such as carbohydrate hydrolases or carbohydrate reductases. Such systems include, but are not limited to, systems that use food ingredients such as non-starch polysaccharides, amylose, xanthan gum, and azopolymers.

[0294] The compositions provided herein can also be delivered to a specific target area, such as the intestine, by orifice (e.g., nasal tube) or surgical delivery. Furthermore, compositions provided herein formulated for delivery to a specific area (e.g., the cecum or colon) may be administered by tube (e.g., directly into the small intestine). Combining a mechanical delivery method, such as a tube, with a chemical delivery method, such as a pH-specific coating, allows the compositions provided herein to be delivered to the desired target area (e.g., the cecum or colon).

[0295] The composition comprising the bacterial strain is formulated into a pharmaceutically acceptable dosage form by conventional methods known to those skilled in the art. The dosing regimen is adjusted to provide the optimal desired response (e.g., prophylactic or therapeutic effect). In some embodiments, the composition is in the form of a tablet, pill, capsule, powder, granules, solution, or suppository. In some embodiments, the pharmaceutical composition is formulated for oral administration. In some embodiments, the pharmaceutical composition is formulated so that the bacteria or portions thereof of the composition remain viable after passing through the subject's stomach. In some embodiments, the pharmaceutical composition is formulated for rectal administration, e.g., as a suppository. In some embodiments, the pharmaceutical composition is formulated for delivery to the intestine or a specific region of the intestine (e.g., the colon) by providing an appropriate coating (e.g., a pH-specific coating, a coating that can be degraded by a target region-specific enzyme, or a coating that can bind to a receptor present in the target region).

[0296] The dosage of the active ingredient in the pharmaceutical compositions disclosed herein can be varied to obtain an amount of the active ingredient effective to achieve the desired pharmaceutical response for a particular subject, composition, and mode of administration, without toxic or adverse effects on the subject. The selected dosage level will depend on various factors, including the activity of the particular composition used, 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 used, the age, sex, weight, condition, general health, and previous medical history of the subject being treated, etc.

[0297] A physician, veterinarian, or other trained practitioner may start a dose of a pharmaceutical composition at a level lower than that required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. Generally, the effective dose of a composition described herein for prophylactic or therapeutic treatment of a human population will vary depending on many different factors, including the route of administration, the physiological condition of the subject, whether the subject is human or animal, other drugs being administered, and the desired therapeutic effect. Dosages may need to be titrated to optimize safety and efficacy. In some embodiments, the dosing regimen involves oral administration of a dose of any of the compositions described herein. In some embodiments, the dosing regimen involves oral administration of multiple doses of any of the compositions described herein. In some embodiments, the composition is orally administered to a subject one, two, three, four, five, six, seven, eight, nine, or at least ten times. In some embodiments, any of the compositions described herein is administered to a subject in multiple doses at regular intervals, such as every two weeks, every month, every two months, every three months, every four months, every five months, every six months, or more.

[0298] The compositions, including pharmaceutical compositions, disclosed herein include compositions containing selected bacterial strains. The amount of bacteria, including the amount of bacterial cells of each bacterial strain in a composition, including a pharmaceutical composition, may be expressed as weight, number of bacteria, and / or CFU (colony forming units). In some embodiments, the compositions, including pharmaceutical compositions, contain about 10, about 10 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 compositions, including pharmaceutical compositions, contain about 10, about 10, or more of each bacterial strain 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 further be understood that bacteria of each bacterial strain may be present in different amounts. Thus, by way of example and not by way of limitation, the composition may comprise 10 or more total bacterial cells. 3 Bacteria A, 10 4 Bacteria B and 10 6 In some embodiments, the compositions, including pharmaceutical compositions, may contain about 10, about 10, or about 10 bacteria C 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 compositions, including pharmaceutical compositions, contain about 10 bacterial cells or CFU of each bacterial strain per dose. 1 , about 10 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 The compositions, including pharmaceutical compositions, contain about 10% or more total bacterial cells or CFU of all of the combined bacterial strains. As noted above, the bacteria of each bacterial strain may be present in different amounts. In some embodiments, the compositions, including pharmaceutical compositions, contain about 10% or more total bacterial cells or CFU of each bacterial strain in the composition. -7 , about 10 -6 , about 10 -5 , about 10 -4 , about 10 -3 , about 10 -2 , about 10 -1 In some embodiments, the compositions, including pharmaceutical compositions, contain about 10 or more grams of bacteria (bacterial cells or CFU) per dose for all bacterial strains combined. -7 , about 10 -6 , about 10 -5 , about 10 -4 , about 10 -3 , about 10 -2 , about 10 -1 Contains 100 or more grams of bacteria (bacterial cells or CFU).

[0299] In some embodiments, a dose is one administration device (e.g., one table, pill, or capsule). In some embodiments, a dose is an amount administered at one time, which may be in the form of two or more administration devices (e.g., two or more tables, pills, or capsules). In some embodiments, a dose is an amount administered over a specific period of time (e.g., one day or one week).

[0300] As described herein, any of the pharmaceutical compositions described herein may be administered once as a single dose.In some embodiments, the pharmaceutical compositions described herein are administered multiple times.In some embodiments, each dose is administered in the form of one or more capsules.In some embodiments, each dose comprises the administration of multiple capsules.In some embodiments, each dose is administered in the form of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more capsules.

[0301] In some embodiments, each capsule contains 10 to 10 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 13 pieces, 10 7 ~10 13 pieces, 10 8 ~10 13 pieces, 10 9 ~10 13 pieces, 10 10 ~10 13 pieces, 10 11 ~10 13 pieces, 10 12 ~10 13 pieces, 10~10 12 pieces, 10 2 ~10 12 pieces, 10 3 ~10 12 pieces, 10 4 ~10 12 pieces, 10 5 ~10 12 pieces, 10 6 ~10 12 pieces, 10 7 ~10 12 pieces, 10 8 ~10 12 pieces, 10 9 ~10 12 pieces, 10 10~10 12 10 11 ~10 12個、 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 pieces, 10 5 ~10 8 pieces, 10 6 ~10 8 pieces, 10 7 ~10 8 pieces, 10~10 7 pieces, 10 2 ~10 7 pieces, 10 3 ~10 7 pieces, 10 4 ~10 7 pieces, 10 5 ~10 7 pieces, 10 6 ~10 7 pieces, 10~10 6 pieces, 10 2 ~10 6 pieces, 10 3 ~10 6 pieces, 10 4 ~10 6 pieces, 10 5 ~10 6 pieces, 10~10 5 pieces, 10 2 ~10 5 pieces, 10 3 ~10 5 pieces, 10 4 ~10 5 pieces, 10~10 4 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 containing bacterial cells or CFU of each bacterial strain.

[0302] In some embodiments, each capsule contains 10 to 10 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 1310 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個、 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 ~105 pieces, 10 3 ~10 5 pieces, 10 4 ~10 5 pieces, 10~10 4 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 In some embodiments, each capsule contains 10 total bacterial cells or CFU. 7 ~10 pieces 9 pieces, 10 7 ~10 pieces 8 Pieces or 10 8 ~10 pieces 9 In some embodiments, each capsule contains about 1.0x10 total bacteria. 7 pieces, 2.0x10 7 pieces, 3.0x10 7 pieces, 4.0x10 7 pieces, 5.0x10 7 pieces, 6.0x10 7 pieces, 7.0x10 7 pieces, 8.0x10 7 pieces, 9.0x10 7 pieces, 1.0x10 8個、 2.0x10 8 pieces, 3.0x10 8 pieces, 4.0x10 8 pieces, 5.0x10 8 pieces, 6.0x10 8 pieces, 7.0x10 8 pieces, 8.0x10 8 pieces, 9.0x10 8 pieces, 1.0x10 9 pieces, 1.1x10 9 pieces, 1.2x10 9 pieces, 1.3x10 9 pieces, 1.4x10 9 pieces, 1.5x10 9 pieces, 1.6x10 9 pieces, 1.7x10 9 pieces, 1.8x10 9 pieces, 1.9x10 9 pieces, 2.0x109 pieces, 2.1x10 9 pieces, 2.2x10 9 pieces, 2.3x10 9 pieces, 2.4x10 9 pieces, 2.5x10 9 pieces, 2.6x10 9 pieces, 2.7x10 9 pieces, 2.8x10 9 pieces, 2.9x10 9 pieces, 3.0x10 9 pieces, 3.1x10 9 pieces, 3.2x10 9 pieces, 3.3x10 9 pieces, 3.4x10 9 pieces, 3.5x10 9 pieces, 3.6x10 9 pieces, 3.7x10 9 pieces, 3.8x10 9 pieces, 3.9x10 9 pieces, 4.0x10 9 pieces, 4.1x10 9 pieces, 4.2x10 9 pieces, 4.3x10 9 pieces, 4.4x10 9 pieces, 4.5x10 9 pieces, 4.6x10 9 pieces, 4.7x10 9 pieces, 4.8x10 9 pieces, 4.9x10 9 pieces, 5.0x10 9 Contains total bacterial cells or CFU.

[0303] In some embodiments, each capsule contains 10 to 10 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 13 pieces, 10 7 ~10 13 pieces, 10 8 ~10 13 pieces, 10 9 ~1013 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個、 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 10 108 ~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 10~104 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 containing bacterial cells or CFU of each bacterial strain.

[0304] In some embodiments, the pharmaceutical composition contains 10 to 10 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 13 pieces, 10 7 ~10 13 pieces, 10 8 ~10 13 pieces, 10 9 ~10 13 pieces, 10 10 ~10 13 pieces, 10 11 ~10 13 pieces, 10 12 ~10 13 pieces, 10~10 12 pieces, 10 2 ~10 12 pieces, 10 3 ~10 12 pieces, 10 4 ~10 12 pieces, 10 5 ~10 12 pieces, 10 6 ~10 12 pieces, 10 7 ~10 12 pieces, 10 8 ~10 12 pieces, 10 9 ~10 12 pieces, 10 10 ~10 12 pieces, 10 11 ~10 12個、 10~10 11 pieces, 102 ~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 ~108 pieces, 10 7 ~10 8 pieces, 10~10 7 pieces, 10 2 ~10 7 pieces, 10 3 ~10 7 pieces, 10 4 ~10 7 pieces, 10 5 ~10 7 pieces, 10 6 ~10 7 pieces, 10~10 6 pieces, 10 2 ~10 6 pieces, 10 3 ~10 6 pieces, 10 4 ~10 6 pieces, 10 5 ~10 6 pieces, 10~10 5 pieces, 10 2 ~10 5 pieces, 10 3 ~10 5 pieces, 10 4 ~10 5 pieces, 10~10 4 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 In some embodiments, the pharmaceutical composition contains 10 to 10 CFU of each bacterial strain per dose. 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 13 pieces, 10 7 ~10 13 pieces, 10 8 ~10 13 pieces, 10 9 ~10 13 pieces, 1010 ~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個、 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 ~1010 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 4 102 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 Contains total bacterial cells or CFU.

[0305] In some embodiments, the compositions disclosed herein contain 10 to 10 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 13 pieces, 10 7 ~10 13 pieces, 10 8 ~10 13 pieces, 10 9 ~10 13 pieces, 10 10 ~10 13 pieces, 10 11 ~10 13 pieces, 10 12 ~10 13 pieces, 10~10 12 pieces, 10 2 ~10 12 pieces, 10 3 ~10 12 pieces, 10 4 ~10 12 pieces, 10 5 ~10 12 pieces, 10 6 ~10 12 pieces, 10 7 ~10 12 pieces, 10 8 ~10 12 pieces, 10 9 ~10 12 pieces, 10 10 ~10 12 pieces, 10 11 ~10 12個、 10~10 11 pieces, 10 2 ~10 1110 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 pieces, 10~10 7 pieces, 10 2 ~10 7 pieces, 10 3 ~10 7 pieces, 10 4 ~10 7 pieces, 10 5 ~10 7 pieces, 10 6 ~10 7 pieces, 10~10 6 pieces, 10 2 ~10 6 pieces, 10 3 ~10 6 pieces, 10 4 ~10 6 pieces, 10 5 ~10 6 pieces, 10~10 5 pieces, 10 2 ~10 5 pieces, 10 3 ~10 5 pieces, 10 4 ~10 5 pieces, 10~10 4 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 Contains total bacteria or colony forming units / ml.

[0306] In some embodiments, the compositions disclosed herein contain 10 to 10 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 13 pieces, 10 7 ~10 13 pieces, 10 8 ~10 13 pieces, 10 9 ~1013 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個、 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 10 108 ~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 10~104 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 In some embodiments, the compositions disclosed herein contain 10 to 10 bacterial cells or colony forming units of bacteria. 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 13 pieces, 10 7 ~10 13 pieces, 10 8 ~10 13 pieces, 10 9 ~10 13 pieces, 10 10 ~10 13 pieces, 10 11 ~10 13 pieces, 10 12 ~10 13 pieces, 10~10 12 pieces, 10 2 ~10 12 pieces, 10 3 ~10 12 pieces, 10 4 ~10 12 pieces, 10 5 ~10 12 pieces, 10 6 ~10 12 pieces, 10 7 ~10 12 pieces, 10 8 ~10 12 pieces, 10 9 ~10 12 pieces, 10 10 ~10 12 pieces, 10 11 ~10 12個、 10~10 11 pieces, 10 2 ~10 11 pieces, 103 ~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 ~108 pieces, 10~10 7 pieces, 10 2 ~10 7 pieces, 10 3 ~10 7 pieces, 10 4 ~10 7 pieces, 10 5 ~10 7 pieces, 10 6 ~10 7 pieces, 10~10 6 pieces, 10 2 ~10 6 pieces, 10 3 ~10 6 pieces, 10 4 ~10 6 pieces, 10 5 ~10 6 pieces, 10~10 5 pieces, 10 2 ~10 5 pieces, 10 3 ~10 5 pieces, 10 4 ~10 5 pieces, 10~10 4 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 of bacteria or bacterial colony forming units / ml.

[0307] In some embodiments, a composition including two or more bacterial strains may contain the same amount of each bacterial strain in terms of bacterial cells or CFU. For example, a composition of the invention comprising Collinsella aerofaciens and Bifidobacterium longum may contain 1 x 10 per milliliter. 8 1 x 10 CFU of Collinsella aerofaciens and 1 x 10 8 May contain 1 x 10 CFU of Bifidobacterium longum per milliliter or 1 x 10 8 Collinsella aerofaciens cells and 1 x 108 May contain Bifidobacterium longum cells.

[0308] In some embodiments, the pharmaceutical composition contains at least 1.6×10 9 In some embodiments, the pharmaceutical composition comprises at least 1.6 x 10 total CFU. 9 In some embodiments, the pharmaceutical composition contains at least 1.6 x 10 total CFU and is administered as a single dose. 9 In some embodiments, the pharmaceutical composition contains at least 1.6 x 10 total CFU and is administered in multiple (e.g., 2, 3, 4, 5, or more) doses. 9 total CFU and are administered in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. In some embodiments, each of the multiple doses is administered at regular intervals. In some embodiments, each of the multiple doses is on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.).

[0309] In some embodiments, the pharmaceutical composition contains at least 4.0x10 9 In some embodiments, the pharmaceutical composition comprises at least 4.0 x 10 total CFU. 9 In some embodiments, the pharmaceutical composition contains at least 4.0 x 10 total CFU and is administered as a single dose. 9 In some embodiments, the pharmaceutical composition contains at least 4.0 x 10 total CFU and is administered in multiple (e.g., 2, 3, 4, 5, or more) doses. 10 total CFU and are administered in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. In some embodiments, each of the multiple doses is administered at regular intervals. In some embodiments, each of the multiple doses is on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.).

[0310] In some embodiments, the pharmaceutical composition comprises at least 8.0x10 9 In some embodiments, the pharmaceutical composition comprises at least 8.0 x 10 total CFU. 9 In some embodiments, the pharmaceutical composition contains at least 8.0 x 10 total CFU and is administered as a single dose. 9 In some embodiments, the pharmaceutical composition contains at least 8.0 x 10 total CFU and is administered in multiple (e.g., 2, 3, 4, 5, or more) doses. 9 total CFU and are administered in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. In some embodiments, each of the multiple doses is administered at regular intervals. In some embodiments, each of the multiple doses is on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.).

[0311] In some embodiments, the pharmaceutical composition contains at least 2.8×10 10 In some embodiments, the pharmaceutical composition comprises at least 2.8 x 10 total CFU. 10 In some embodiments, the pharmaceutical composition contains at least 2.8 x 10 total CFU and is administered as a single dose. 10 In some embodiments, the pharmaceutical composition contains at least 2.8 x 10 total CFU and is administered in multiple (e.g., 2, 3, 4, 5, or more) doses. 10 In some embodiments, the pharmaceutical composition contains at least 2.8 x 10 total CFU and is administered in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. 10 The multiple doses comprise a total of 7 CFU and are administered as 7 doses. In some embodiments, each of the multiple doses is administered at regular intervals. In some embodiments, each of the multiple doses is on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.).

[0312] In some embodiments, the pharmaceutical composition contains at least 4.0 x 10 10 In some embodiments, the pharmaceutical composition comprises at least 4.0 x 10 total CFU. 10 In some embodiments, the pharmaceutical composition contains at least 4.0 x 10 total CFU and is administered as a single dose. 10 In some embodiments, the pharmaceutical composition contains at least 4.0 x 10 total CFU and is administered in multiple (e.g., 2, 3, 4, 5, or more) doses. 10 In some embodiments, the pharmaceutical composition contains at least 4.0 x 10 total CFU and is administered in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. 10 The pharmaceutical composition contains at least 4.0 x 10 total CFU and is administered as 5 doses. In some embodiments, each of the multiple doses is administered at regular intervals. In some embodiments, each of the multiple doses is on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.). In some embodiments, the pharmaceutical composition contains at least 4.0 x 10 10 total CFU and is administered as five doses, each administered on five consecutive days.

[0313] In some embodiments, the pharmaceutical composition contains at least 5.6×10 10 In some embodiments, the pharmaceutical composition comprises at least 5.6 x 10 total CFU. 10 In some embodiments, the pharmaceutical composition contains at least 5.6 x 10 total CFU and is administered as a single dose. 10 In some embodiments, the pharmaceutical composition contains at least 5.6 x 10 total CFU and is administered in multiple (e.g., 2, 3, 4, 5, or more) doses. 10 In some embodiments, the pharmaceutical composition contains at least 5.6 x 10 total CFU and is administered in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses.10 The pharmaceutical composition contains at least 5.6 x 10 total CFU and is administered as 14 doses. In some embodiments, each of the multiple doses is administered at regular intervals. In some embodiments, each of the multiple doses is on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.). In some embodiments, the pharmaceutical composition contains at least 5.6 x 10 10 total CFU and is administered as 14 doses, each administered on 14 consecutive days.

[0314] In some embodiments, the pharmaceutical composition contains at least 1.1 x 10 11 In some embodiments, the pharmaceutical composition comprises at least 1.1 x 10 total CFU. 11 In some embodiments, the pharmaceutical composition contains at least 1.1 x 10 total CFU and is administered as a single dose. 11 In some embodiments, the pharmaceutical composition contains at least 1.1 x 10 total CFU and is administered in multiple (e.g., 2, 3, 4, 5, or more) doses. 11 In some embodiments, the pharmaceutical composition contains at least 1.1 x 10 total CFU and is administered in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. 11 The pharmaceutical composition contains at least 1.1 x 10 total CFU and is administered as 14 doses. In some embodiments, each of the multiple doses is administered at regular intervals. In some embodiments, each of the multiple doses is on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.). In some embodiments, the pharmaceutical composition contains at least 1.1 x 10 11 total CFU and is administered as 14 doses, each administered on 14 consecutive days.

[0315] In some embodiments, the pharmaceutical composition contains at least 2.1 x 10 10 In some embodiments, the pharmaceutical composition comprises at least 2.1 x 10 total CFU. 10In some embodiments, the pharmaceutical composition contains at least 2.1 x 10 total CFU and is administered as a single dose. 10 In some embodiments, the pharmaceutical composition contains at least 2.1 x 10 total CFU and is administered in multiple (e.g., 2, 3, 4, 5, or more) doses. 10 In some embodiments, the pharmaceutical composition contains at least 2.1 x 10 total CFU and is administered in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. 10 The pharmaceutical composition contains at least 2.1 x 10 total CFU and is administered as 5 doses. In some embodiments, each of the multiple doses is administered at regular intervals. In some embodiments, each of the multiple doses is on consecutive days (e.g., a first dose on day 1, a second dose on day 2, a third dose on day 3, etc.). In some embodiments, the pharmaceutical composition contains at least 2.1 x 10 10 total CFU and is administered as five doses, each administered on five consecutive days.

[0316] As described herein, any of the pharmaceutical compositions described herein may be administered to a subject in one or more doses (e.g., an initial administration), followed by one or more additional doses of any of the pharmaceutical compositions described herein. In some embodiments, any of the pharmaceutical compositions described herein may be administered to a subject in one or more initial doses, followed by one or more additional doses of a pharmaceutical composition comprising the same one or more bacterial strains as the initial pharmaceutical composition. In some embodiments, any of the pharmaceutical compositions described herein may be administered to a subject in one or more initial doses, followed by one or more additional doses of a pharmaceutical composition comprising more total bacteria (colony-forming units) than the initial administration of the pharmaceutical composition. In some embodiments, any of the pharmaceutical compositions described herein may be administered to a subject in one or more initial doses, followed by one or more additional doses of a pharmaceutical composition comprising fewer total bacteria (colony-forming units) than the initial administration of the pharmaceutical composition. In some embodiments, the initial administration comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses of any pharmaceutical composition described herein. In some embodiments, the additional administration comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses of any pharmaceutical composition described herein. In some embodiments, the initial administration comprises two doses of any pharmaceutical composition and the additional administration comprises three doses of any pharmaceutical composition described herein.

[0317] In some embodiments, any pharmaceutical composition described herein may be administered to a subject in one or more initial doses, followed by one or more additional doses of the pharmaceutical composition containing fewer total bacteria (colony forming units) compared to the initial dose of the pharmaceutical composition. In such embodiments, the initial dose(s) may be referred to as the "high dose," and the additional dose(s) may be referred to as the "low dose." In some embodiments, the high dose is at least 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more times more potent than the low dose. In some embodiments, the high dose is 8.0 x 10 9 In some embodiments, the low dose is 1.6 x 10 CFU. 9 In some embodiments, the initial dose is 8.0 x 10 CFU. 9 Includes multiple doses of CFU (e.g., 2, 3, 4, 5 or more), with booster doses of 1.6 × 10 9 In some embodiments, a low dose includes multiple doses (e.g., 2, 3, 4, 5 or more) of CFU. 9 In some embodiments, the initial dose is 8.0 x 10 CFU. 9 Contains two doses of CFU, with a booster dose of 1.6 × 10 9 Contains three doses of CFU.

[0318] In some embodiments, one or more additional administrations are administered the day after the first administration (e.g., on consecutive days). In some embodiments, one or more additional administrations are administered at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, or more after the first administration. In some embodiments, one or more additional administrations are administered at least 6 weeks after the first administration. In some embodiments, one or more additional administrations are administered at least 12 weeks after the first administration.

[0319] In some embodiments, compositions, including pharmaceutical compositions, contain 10 to 10 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 13 pieces, 10 5 ~10 13 pieces, 10 6 ~10 13 pieces, 10 7 ~10 13 pieces, 10 8 ~10 13 pieces, 10 9 ~10 13 pieces, 10 10 ~10 13 pieces, 10 11 ~10 13 pieces, 10 12 ~10 13 pieces, 10~10 12 pieces, 10 2 ~10 12 pieces, 10 3 ~10 12 pieces, 10 4 ~10 12 pieces, 10 5 ~10 12 pieces, 10 6 ~10 12 pieces, 10 7 ~1012 10 8 ~10 12 10 9 ~10 12 10 10 ~10 12 10 11 ~10 12個、 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 10~108 pieces, 10 2 ~10 8 pieces, 10 3 ~10 8 pieces, 10 4 ~10 8 pieces, 10 5 ~10 8 pieces, 10 6 ~10 8 pieces, 10 7 ~10 8 pieces, 10~10 7 pieces, 10 2 ~10 7 pieces, 10 3 ~10 7 pieces, 10 4 ~10 7 pieces, 10 5 ~10 7 pieces, 10 6 ~10 7 pieces, 10~10 6 pieces, 10 2 ~10 6 pieces, 10 3 ~10 6 pieces, 10 4 ~10 6 pieces, 10 5 ~10 6 pieces, 10~10 5 pieces, 10 2 ~10 5 pieces, 10 3 ~10 5 pieces, 10 4 ~10 5 pieces, 10~10 4 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 In some embodiments, compositions, including pharmaceutical compositions, contain 10 to 10 bacterial cells or CFU of each bacterial strain per dose. 13 pieces, 10 2 ~10 13 pieces, 10 3 ~10 13 pieces, 10 4 ~10 1310 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個、 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 6 105 ~10 6 pieces, 10~10 5 pieces, 10 2 ~10 5 pieces, 10 3 ~10 5 pieces, 10 4 ~10 5 pieces, 10~10 4 pieces, 10 2 ~10 4 pieces, 10 3 ~10 4 pieces, 10~10 3 pieces, 10 2 ~10 3 Pieces or 10 to 10 2 Contains total bacterial cells or CFU.

[0320] In some embodiments, the composition, including the pharmaceutical composition, comprises 10 -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, compositions, including pharmaceutical compositions disclosed herein, contain 10 grams of bacteria of each bacterial strain 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 all (total) bacteria combined in grams.

[0321] Aspects of the present disclosure also provide a food product comprising any of the compositions described herein and nutrients. Also included within the scope of the present disclosure are foods comprising any of the bacterial strains described herein and nutrients. In some embodiments, the food product may further comprise taurine. The food product is generally intended for human or animal consumption. Any of the bacterial strains described herein may be formulated as a food product. In some embodiments, the bacterial strain is formulated as a spore-form food product. In some embodiments, the bacterial strain is formulated as a nutritional food product. In some embodiments, the food product comprises both nutritional and spore-form bacteria. The compositions disclosed herein may be used in foods or beverages such as health foods or beverages, foods or beverages for infants, foods or beverages for pregnant women, athletes, the elderly, or other specific groups, functional foods, beverages, foods or beverages for specific health uses, dietary supplements, foods or beverages for patients, or animal feed.

[0322] Non-limiting examples of foods and beverages include various beverages such as juices, soft drinks, tea drinks, beverage preparations, jelly drinks, and functional drinks; alcoholic beverages such as beer; carbohydrate-containing foods such as rice foods, noodles, bread, and pasta; fish ham, sausage, and seafood paste products; retort pouch products such as curry, foods dressed with thick starch sauces, soups; dairy products such as milk, dairy drinks, ice cream, cheese, and yogurt; fermented products such as fermented soybean paste, yogurt, fermented drinks, and pickles; soy products; Western confectionery products such as biscuits and cookies; Japanese confectionery products such as steamed bean paste buns and soft red bean jelly; various confectionery products such as candy, chewing gum, gummies, and frozen desserts including jellies, cream caramel, and frozen desserts; instant foods such as instant soups and instant soybean soups; microwaveable foods; and health foods and beverages prepared in the form of powders, granules, tablets, capsules, liquids, pastes, jellies, and the like.

[0323] Food products containing the bacterial strains described herein may be produced using methods known in the art and may contain the same amounts of bacteria (e.g., weight, quantity, or CFU) as the pharmaceutical compositions provided herein. Selecting the appropriate amount of bacteria in a food product may depend on various factors, including, 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.

[0324] Examples of food products that may be formulated to contain any of the bacterial strains described herein include, but are not limited to, beverages, drinks, bars, snacks, dairy products, confectionery products, cereal products, ready-to-eat products, nutritional formulas such as dietary supplements, and food or beverage additives. [Table 1-1] [Table 1-2]

[0325] array SEQ ID NO: 1 Collinsella aerofaciens_F strain 1

[0326] SEQ ID NO: 2 Bacteroides xylanisolvens strain 2

[0327] SEQ ID NO: 3 Alistipes putredinis strain 3

[0328] SEQ ID NO: 4 Alistipes shahii strain 4

[0329] SEQ ID NO: 5 Eubacterium_E hallii strain 5

[0330] SEQ ID NO: 6 Blautia_A obeum strain 6

[0331] SEQ ID NO: 7 Odoribacter splanchnicus strain 7

[0332] SEQ ID NO: 8 Bacteroides cellulosilyticus strain 8

[0333] SEQ ID NO: 9 Bacteroides uniformis strain 9

[0334] Bacteroides_B vulgatus strain 10

[0335] SEQ ID NO: 11 Bacteroides fragilis strain 11

[0336] SEQ ID NO: 12 Bacteroides caccae strain 12

[0337] SEQ ID NO: 13 Paeniclostridium sordellii strain 13

[0338] SEQ ID NO: 14 Blautia producta strain 14

[0339] SEQ ID NO: 15 Absiella innocuum strain 15

[0340] SEQ ID NO: 16 Clostridium_M clostridioforme strain 16

[0341] SEQ ID NO: 17 Paraclostridium massiliensis strain 17

[0342] SEQ ID NO: 18 Dorea longicatena B strain 18

[0343] SEQ ID NO: 19 Bacteroides thetaiotaomicron strain 19

[0344] SEQ ID NO: 20 Parabacteroides distasonis strain 20

[0345] SEQ ID NO: 21 Escherichia coli strain 21

[0346] SEQ ID NO: 22 Bifidobacterium longum strain 22

[0347] SEQ ID NO: 23 Absiella innocuum strain 23

[0348] SEQ ID NO: 24 Fusobacterium_A sp strain 24

[0349] SEQ ID NO: 25 Parabacteroides merdae strain 25

[0350] SEQ ID NO: 26 Coprococcus_B comes strain 26

[0351] SEQ ID NO: 27 Agathobacter rectale strain 27

[0352] SEQ ID NO: 28 Erysipelatoclostridium ramosum strain 28

[0353] SEQ ID NO: 29 Clostridium_M citroniae strain 29

[0354] SEQ ID NO: 30 Bacteroides faecis strain 30

[0355] SEQ ID NO: 31 Bacteroides ovatus strain 31

[0356] SEQ ID NO: 32 Bifidobacterium pseudocatenulatum strain 32

[0357] SEQ ID NO: 33 Anaerostipes caccae strain 33

[0358] SEQ ID NO: 34 Bifidobacterium adolescentis strain 34

[0359] SEQ ID NO: 35 Agathobaculum sp. MUR_P3C8a strain 35

[0360] SEQ ID NO: 36 Phascolarctobacterium faecium MUR_P6E9 strain 36

[0361] SEQ ID NO: 37 Akkermansia muciniphila strain 37

[0362] SEQ ID NO: 38 Barnesiella intestinihomins strain 38

[0363] SEQ ID NO: 39 Bilophila wadsworthia strain 39

[0364] SEQ ID NO: 40 Blautia faecis strain 40

[0365] SEQ ID NO: 41 Blautia wexlerae strain 41

[0366] SEQ ID NO: 42 Blautia luti strain 42

[0367] SEQ ID NO: 43 Butyricimonas synergistica strain 43

[0368] SEQ ID NO: 44 Clostridium bolteae strain 44

[0369] SEQ ID NO: 45 Parasutterella excrementihominis strain 45

[0370] SEQ ID NO: 46 Prevotella copri strain 46

[0371] SEQ ID NO: 47 Ruminococcus faecis strain 47

[0372] SEQ ID NO: 48 Bacteroides caccae

[0373] Accession No. 49 Bacteroides cellulosilyticus / Bacteroides intestinalis

[0374] SEQ ID NO: 50 Bacteroides faecis

[0375] SEQ ID NO: 51 Bacteroides ovatus CGATATCCGGATTTATTGGAGTTT-AAGGGAGCGTAGGTGGATTGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGAAACTGGCAGTCTTGAGTACAGTAGAGGTGGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTAGACTGTCACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAACAGAATATATTGGAAACAGTATAGCCGTAAGGCTGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTKATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCSGCTACCTGGTGACAGGATGCTAATCCCAAAAACCTCTCTCAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGGGTAAAACTGGTAATTGGGGC

[0376] Accession number 52 Bacteroides thetaiotaomicron TTTAAGGGAGCGTAGGTGGACAGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGCTGTCTTGAGTACAGTAGAGGTGGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCWAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAWWTGAATAWWYTGGAAACAGKWTAGYCGYAAGRCAWWTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTACCTGGTGACAGGATGCTAATCCCAAAAGCCTCTCTCAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTACGTAACCGCA

[0377] Accession number 53 Bacteroides uniformis

[0378] SEQ ID NO: 54 Bacteroides vulgatus

[0379] Accession number 55 Bifidobacterium adolescentis GGGCTCGTAGKCGGTTCGTCGCGTCCGGTGTGAAAGTCCAYCGCTTAACGGTGGATCCGCGCCGGGTACGGGCGGGCTTGAGTGCGGTAGGGGAGACTGGAATTCCCGGTGTAACGGTGGAATGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTGGGCCGTCACTGACGCTGAGGAGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGACCATTCCACGGTCTCCGTGTCGGAGCCAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGAAATTGACGGGGGCCCGCACAAGCGGCGGAGCATGCGGATTAATTCGATGCAACGCGAAGAACCTTACCTGGGCTTGACATGTTCCCGACAGCCCCAGAGATGGGGCCTCCCTTCGGGGCGGGTTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGTCGTGGTGGGAACTCACGGGGGACCGCCGGGGTCAACTCGGAGGAAGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTCCAGGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGCGACACT-GTGAGGTGGAGCGGATCCCTTAAAACCGGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGGCGGAGTCGCTAGTAATCGCGGATCAGCAACGCCGCGGTGAATGCGTTCCCGGGCCTTGTACACACCGCCCGTCAAGTCATGAAAGTGGGTAGCACCCGAAGCCGGTGGCCCATCCTTTTTGGGG

[0380] SEQ ID NO: 56 Bifidobacterium longum

[0381] Accession number 57 Bifidobacterium pseudocatenulatum GGTTCGTCGCGTCCGGTGTGAAAGTCCATCGTTTAACGGTGGATCTGCGCCGGGTACGGGCGGGCTGGAGTGCGGTAGGGGAGACTGGAATTCCCGGTGTAACGGTGGAATGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTGGGCCGTTACTGACGCTGAGGAGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGCCCGTTCCACGGGTTCCGTGWCGGAGCTAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACWMAAAKAAATTGACGGGGGCCCGCACAAGCGGCGGAGCATGCGGATTAATTCGATGCAACGCGAAGAACCTTACCTGGGCTTGACATGTTCCCGACAGCCGTAGAGATATGGCCTCCCTTCGGGGCGGGTTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGTCATGGTGGGAACTCACGGGGGACCGCCGGGGTCAACTCGGAGGAAGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTTCAGGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGCGACACGGCGACGTG

[0382] Accession number 58 Blautia coccoides / Blautia producta

[0383] sequence number 59 Clostridium citroniae TCCGGATTTACTGGAGTAGT-AAGGGAGCGTAGACGGCGAAGCAAGTCTGGAGTGAAAACCCAGGCTCAACCCTGGGACTGCTTTGGAAACTGTTTTGCTAGAGTGTCGGAGAGGTAAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTACTGGACGATAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCA AACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATGCTAGGTGTTGGGGGGCAAAGCCCTTCGGTGCCGTCGCAAACGCAATAAGCATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCCCCTGACCGGT CAGTAAAGTGACCTTTCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTAGTAGCCAGCAGGTAAAGCTGGGCACTCTAGGGAGACTGCCAGGGATAACCTGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAA TGGCGTAAACAAAGGGAAGCGACCCTGCGAAGGCAAGCAAATCCCAAAAATAACGTCCCAGTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCGAATCAGAATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCAACCATGGGAGTCAGCAACGCCCGAAGTCAGTGACCCAACCGAAAGGAGGGAGCTGCCGAA

[0384] SEQ ID NO: 60 Clostridium clostridioforme

[0385] SEQ ID NO: 61 Clostridium innocuum

[0386] SEQ ID NO: 62 Clostridium innocuum / Erysipelotrichaceae bacterium 6_1_45

[0387] Accession number 63 Clostridium sordellii ACACATGCAAGTCGAGCGAACCCTTCGGGGTGAGCGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCCTGTACACACGGATAACATACCGAAAGGTATGCTAATACGGGATRAYATATGAGAGTCGCATGGCTTTTGTATCAAAGCTCCGGCGGTACAGGATGGACCCGCGTCTGATTAGCTAGTTGGTAAGGTAACGGCTTACCAAGGCAACGATCAGTAGCCGACCTGAGAGGGTGATCGGCCACATTGGAACTGAGACACGGTCCAAACTCMTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAGCAACGCCGCGTGAGCGATGAAGGCCTTCGGGTCGTAAAGCTCTGTCCTCAAGGAAGATAATGACGGTACTTGAGGAGGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCTAGCGTTATCCGGAATTACTGGGCGTAAAGGGTGCGTAGGCGGTCTTTCAAGCCAGAAGTGAAAGGCTACGGCTCAACCGTAGTAAGCTTTTGGAACTGTAGGACTTGAGTGCAGGAGAGGAGAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTAGCGAAGGCGGCTCTCTGGACTGTAACTGACGCTGAGGCACGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAGTACTAGGTGTCGGGGGTTACCCCCCTCGGTGCCGCAGCTAACGCATTAAGTACTCCGCCTGGGAAGTACGCTCGCAAGAGTGAAACTCAAAGGAATTGACGGGGACCCGCACAAGTAGCGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTATCTAARCTTGACATC

[0388] Accession number 64 Coprococcus comes ACRGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCRCGTGAGCGAAGAAGTATTKCGGTATGTAAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCACCGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGGTGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGCTGTGTAAGTCTGAAGTGAAAGGCGGGGGCTCCCCCCCGGGGACTGCTTTGGAAACTATGCAGCTAGACTGTCGGACAGGTAAGTGGAATTCCCAGTGTAGCGGTGAAATGCGTAGATATTGGGAGGAACAGCAKTGGGTAAGGCTSCTTACAGGACRAT

[0389] Accession number 65 Dorea longicatena

[0390] Accession number 66 Erysipelatoclostridium ramosum GAGGGAGCAGGCGGCAGCAAGGGTCTGTGGTGAAAGCCTGAAGTTAAACTTCAGTAAGCCATAGAAACCAGGCAGCTAGAGTGCAGGAGAGGAKCGTGGAATTCCATGTGTAGCGGTGAAATGCGTAGATATATGGAGGAACACCAGTGGCGAAGGCGACGATCTGGCCTGCAACTGACGCTCAGTCCCGAAAGCGTGGGGAGCAAATAGGATTAGATACCCTAGTAGTCCACGCCGTAAACGATGAGTACTRAGTGTTGGATGTCAAAGTTCAGTGCTGCAGTTAACGCAATAAGTACTCCGCCTGAGTAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATACTCATAAAGGCTCCAGAGATGGAGAGATAGCTATATGAGATACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCGTTAGTTACCATCATTAAGTTGGGGACTCTAGCGAGACTGCCAGTGACAAGCTGGAGGAARGCGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGATGGTGCAGAGGGAAGCGAAGCCGCGAGGTGAAGCAAAACCCATAAAACCATTCTCAGTTCGGATTGTAGTCTGCARCTCGACTACATGAAGTTGGAATCGCTAGTAATCGCGAATCARCATGTCGCGATGAATAMGTTCTCGGGCCTT

[0391] Accession number 67 Eubacterium rectale

[0392] SEQ ID NO: 68 Odoribacter splanchnicus

[0393] Accession number 69 Parabacteroides distasonis CGAGGGGCAGCRCAGGAGT-TAGCAATAC-CSGGTGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACTTRCCTATCAGAGGGGGATAACCCGGCGAAAGTCGGACTAATACCGCATGAAGCAGGGATYCCGCATGGGRATATTTGCTAAAGATTCATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTGGCGGGGTAACRGCCCACCAAACCGACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGSCGWRAGSCTGAACCAGCCAAGTCGCGTGAGGGATGAAGGTTCTATGGATCGTAAACCTCTTTTATAAGGGAATAAAGTGCGGGACGTGTCCYRTTTTGTATGTACCTTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCCTTTTAAGTCAGCGGTGAAAGTCTGTGGCTCAACCATAGAATTGCCGTTGAAACTGGGGGGCTTGAGTATGTTTGAGGCAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACCCCGWTTGCGAAGGCAGCCTGCCAAGCCGTAACTGACGCGGATGCACGAAAGCGTGGGGATCAAACAGGATTAGATACCCTGGTA

[0394] Accession number 70 Parabacteroides merdae CATGCAAGTCGAGGGGCAGCATGATTTGTAGCAATACAGATTGATGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACTTACCTATCAGAGGGGGATAGCCCGGCGAAAGTCGGATTAATACCCCATAAAACAGGGGTCCCGCATGGGAATATTTGTTAAAGATTCATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCACCAAACCGACGATGGATAGGGGTTCKGAGAGGAAGGTCCCCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGCCGAGAGGCTGAACCAGCCAAGTCGCGTGAAGGAAGAAGGATCTATGGTTTGTAAACTTCTTTTATAGGGGAATAAAGTGGAGGACGTGTCCTTTTTTGTATGTACCCTATGAATAAGCATCGGCTAACTCCGTGMSARCMGCCGCGGGAATACGGAAGATGCAGAGCGTTATCCGGATWTATTGGGGTTA

[0395] Accession No. 71 Bacteroides xylanisolvens

[0396] SEQ ID NO: 72 Blautia obeum

[0397] SEQ ID NO: 73 Alistipes putredinis

[0398] SEQ ID NO: 74 Collinsella aerofaciens

[0399] Sequence number 75 Bacteroides faecis / Eubacterium hallii

[0400] Sequence number 76 Alistipes shahii ACATAGGGGGWSTGWKAGGTTWRCCSCCCACATTSRTACTGAGMCA-TGAWCMAACTCTMTACGGGARGSAGSAGTGAGGAATATTGGTCRRTGGACGCAAGTCTGAACCAGCCATGCCGSGTGCRGGAAGACGGCTCKATGAGTKGKAAACTGCTTTTGTACRARRGTAAACGCTCTTACGTGTAAGAGCCTGAAAGTATSGTACRAATGAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCAAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGGTTGATAAAGTTAGRGG

[0401] Sequence number 77 Anaerostipes caccae GCTT-ACACATG-CAAGTCGAACGAAGCATTTARGATTGAAGTTTTCGGATGGATTTCCTATATGACTGAGTGGCGGACGGGTGAGTAACGCGTGGGGAACCTGCCCTATACAGGGGGATAACAGCTGGAAACGGCTGCTAATACCGCATAAGCGCACAGAATCGCATGATTCAGTGTGAAAAGCCCTGGCAGTATAGGATGGTCCCGCGTCTGATTAGCTGGTTGGTGAGGTAACGGCTCACCAAGGCGACGATCAGTAGCCGGCTTGAGAGAGTGAACGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGG-AAACCCTGATGCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTCTATCAGCAGGGAAGAAAACAGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGAATTACTGGGTGTAAAGGGTGCGTAGGTGGCATGGTAAGTCAGAAGTGAAAGCCCGGGGCTTAACCCCGGGACTGCTTTTGAAACTGTCATGCTGGAGTGCAGGAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACTGTCACTGACACTGATGCACGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGGCCGTAGAGGCTTCGGTGCCGCAGCAAA

[0402] Accession number 78 Phascolarctobacterium faecium CGGAGAATTTTCATTTCGGTAGAATTCTTAGTGGCGAACGGGTGAGTAACGCGTAGGCAACCTGCCCTTTAGACGGGGACAACATTCCGAAAGGAGTGCTAATACCGGATGTGATCATCGTGCCGCATGGCAGGATGAAGAAAGATGGCCTCTACAAGTAAGCTATCGCTAAAGGATGGGCCTGCGTCTGATTAGCTAGTTGGTAGTGTAACGGACTACCAAGGCGATGATCAGTAGCCGGTCTGAGAGGATGAACGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATCTTCCGCAATGGACGAAAGTCTGACAGAGCAACGCCGCGTGAGTGATGAAGGATTTCGGTCTGTAAAGCTCTGTTGTTTATGACGAACGTGCAGTGTGTGAACAATGCATTGCAATGACGGTAGTAAACGAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCGAGCGTTGTCCGGAATTATTGGGCGTAAAGAGCATGTAGGCGGCTTAATAAGTCGAGCGTGAAAAATGCGGGGCTCAACCCCGTATGGCGCTGGAAACTGTTAGGCTTGAGTGCAGGAGAGGAAAGGGGAATTCCCAGTGTAGCGGTGAAATGCGTAGATATTGGGAGGAACACCAGTGGCGAAGGCGCCTTTCTGGACTGTGTTTGACGCTGAGATGCGAAAGCCAGGGTAGC

[0403] Sequence number 79 Agathobaculum butyriciproducens TAGTGGCGGACGGGTGAGTAACGCGTGAGCAATCTGCCTTTAAGAGGGGGATAACAGTCGGAAACGGCTGCTAATACCGCATAAAGCATTGAATTCGCATGTTTTCGATGCCAAAGGAGCAATCCGCTTTTAGATGAGCTCGCGTCTGATTAGCTAGTTGGCGGGGTAACGGCCCACCAAGGCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCGCAATGGGGGRAACCCTGACGCAGCAACGCCGCGTGATTGAAGAAGGCCTTCGGGTTGTAAAGATCTTTAATCAGGGACGAA--AMATGACGGTACCTGAAGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGCGCAGGCGGGCCGGCAAGTTGGAAGTGAAATCCGGGGGCTTAACCCCCGAACTGCTTTCAAAACTGCTGGTCTTGAGTGATGGAGAGGCAGGCGGAATTCCGTGTGTAGCGGTGAAATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTGACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGGATA

[0404] Accession No. 80 Bacteroides fragilis

[0405] SEQ ID NO: 81 Fusobacterium mortiferum

[0406] SEQ ID NO: 82 Paraclostridium benzoelyticum / Clostridium bifermantans

[0407] SEQ ID NO: 83 Escherichia fergusonii / Escherichia coli

[0408] The invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or carried out in various ways. Also, the phraseology and terminology used herein is for purposes of description and should not be regarded as limiting. As used herein, the use of "including," "comprising," "having," "containing," "involving," and variations thereof, is meant to cover the items listed thereafter and equivalents thereof as well as additional items.

[0409] Unless otherwise defined herein, scientific and technical terms used in connection with this disclosure shall have the meanings commonly understood by those of ordinary skill in the art. Furthermore, unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular. The methods and techniques of this disclosure are generally performed in accordance with conventional methods known in the art. Generally, the nomenclature used in connection with, and techniques of, biochemistry, enzymology, molecular and cell biology, microbiology, virology, cell or tissue culture, genetics, and protein and nucleic acid chemistry described herein are those well known and commonly used in the art. The methods and techniques of this disclosure are generally performed in accordance with conventional methods known in the art, unless otherwise indicated, and as described in the various general and more specific references cited and discussed throughout this specification.

[0410] 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 all references cited throughout this application (including literature, issued patents, published patent applications, and co-pending patent applications) are expressly incorporated herein 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.

[0411] Example Example 1: Efficacy of bacterial compositions to decolonize ESBLs. As shown in Figure 1, mice were treated with antibiotics (e.g., 0.5 g / L ampicillin) for 7 days and then challenged with a CRE- or ESBL-producing Enterobacteriaceae challenge (Escherichia coli ATCC BAA-2777, "ESBL"). On day -3, mice were challenged with CRE or ESBL. On days 0, 1, and 2, mice received treatment (e.g., PBS (control), 36-mix live biological therapeutic product (36-mix), or a fecal fraction library from a human donor (Donor 1 SFL)). Fecal samples (pellets) were collected at various time points after treatment to quantify colony-forming units (CFU) as a measure of ESBL colonization levels. The effectiveness of the treatments in reducing CRE or ESBL colonization was evaluated.

[0412] As shown in Figure 2, 36-mix and SFL from donor 1 were able to reduce ESBL colonization levels, but SFL from donor 1 reduced ESBL colonization to a lower level. Some mice treated with 35-mix showed a greater reduction in ESBL colonization. Stool from mice treated with 36-mix and with the lowest levels of ESBL colonization was subjected to metagenomic sequencing, which identified several mouse-derived taxa present in these mice compared with mice receiving 36-mix and higher levels of ESBL colonization.

[0413] Additional bacterial strains were evaluated for combination with the strains in the 36 Mix. A bacterial mixture containing the strains present in the 36 Mix and 11 additional strains was prepared, for a total of 47 bacterial strains (47 Mix). See Figure 3 and Table 1.

[0414] Example 2: Efficacy of a bacterial composition comprising 47 bacterial strains to decolonize CRE and ESBL. Mice were treated with antibiotics (e.g., 0.5 g / L ampicillin) for 7 days prior to challenge with a carbapenem-resistant Klebsiella pneumoniae challenge (Klebsiella pneumoniae ATCC BAA-2814, "CRE") or an ESBL-producing Enterobacteriaceae challenge (Escherichia coli ATCC BAA-2777, "ESBL") (Figure 1). On day -3, mice were challenged with CRE or ESBL. On days 0, 1, and 2, mice received treatment (e.g., PBS (control) or 47 Mix live biological therapeutic product (47 Mix)). Fecal samples (pellets) were collected at various time points after treatment to quantify colony-forming units (CFU) as a measure of CRE or ESBL colonization levels.

[0415] The colonization levels of CRE and ESBL in mice are shown in Figure 4. Administration of the 47-mix bacterial composition reduced both CRE and ESBL by at least 3 logs compared to mice administered the control (PBS).

[0416] Example 3: Efficacy of a bacterial composition comprising 47 bacterial strains to decolonize ESBLs or CREs. Mice were treated with antibiotics (e.g., 0.5 g / L ampicillin) for 7 days before challenge with carbapenem-resistant Klebsiella pneumoniae (Klebsiella pneumoniae ATCC BAA-2814, "CRE") or ESBL-producing Enterobacteriaceae (Escherichia coli ATCC BAA-2777, "ESBL") (Figure 1). On day -3, mice were challenged with CRE or ESBL. On days 0, 1, and 2, mice were administered treatments (e.g., PBS (control), 47 Mix live biotherapeutic product (47 Mix), a stool fraction library obtained by culturing stool from a second human donor (Donor 2 SFL), or a bacterial mixture obtained by introducing stool from a first human donor (Donor 1) into mice and obtaining stool from the mice) to prepare fecal component grafts (Donor 1-inoculated mouse FMT).

[0417] Fecal samples (pellets) were collected at various time points after treatment to quantify colony-forming units (CFU) as a measure of CRE or ESBL colonization levels. ESBL and CRE colonization levels in mice are shown in Figures 5A and 5B, respectively.

[0418] Administration of the 47-mix bacterial composition resulted in at least a 2-log reduction in both ESBL and CRE colonization by day 7. Both ESBL and CRE colonization were further reduced at both 10 and 14 days after treatment.

[0419] Example 4: Efficacy of bacterial compositions containing bacterial strains and taurine to decolonize ESBLs or CREs Mice are treated with antibiotics (e.g., 0.5 g / L ampicillin) for 7 days prior to challenge with a carbapenem-resistant Klebsiella pneumoniae challenge (Klebsiella pneumoniae ATCC BAA-2814, "CRE") or an ESBL-producing Enterobacteriaceae challenge (Escherichia coli ATCC BAA-2777, "ESBL"). On day 3, mice are challenged with CRE or ESBL. Mice are administered the following treatment conditions: -PBS (control), -PBS + taurine (taurine only), a live biotherapeutic product (any of the compositions described herein), and -Living biological therapeutic product + taurine (any of the compositions described herein + taurine).

[0420] Taurine may be administered in the same composition as the live biological therapeutic product or may be administered in a separate composition, and may be administered before, simultaneously with, or after administration of the live biological therapeutic product.

[0421] At various time points after treatment, fecal samples (pellets) are collected and colony forming units (CFU) are quantified as a measure of the level of CRE or ESBL colonization.

Claims

[Claim 1] The invention described herein.

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