Compositions and methods for maintaining and restoring a healthy gut barrier

Abstract

The present invention relates to, in part, compositions and methods for delivery of novel mixtures of bacterial strains for maintaining and/or restoring a healthy gut barrier.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a bacterial mixture wherein at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one of the operational taxonomic units (OTUs) recited in Table 5. 
     
     
         2 . A pharmaceutical composition comprising a bacterial mixture wherein at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one operational taxonomic unit (OTU) of a genus recited in Table 6. 
     
     
         3 . The pharmaceutical composition of  claim 1  or  claim 2 , wherein the 16S rRNA sequence of the at least one bacterial strain in the bacterial mixture is greater than about 98% identical to the 16S rRNA sequence of any one of the OTUs recited in Table 5 of or any one OTU of a genus recited in Table 6. 
     
     
         4 . The pharmaceutical composition of any one of  claims 1  to  3 , wherein the 16S rRNA sequence of the at least one bacterial strain in the bacterial mixture is greater than about 99% identical to the 16S rRNA sequence of any one of the OTUs recited in Table 5 or of any one OTU of a genus recited in Table 6. 
     
     
         5 . The pharmaceutical composition of any one of  claims 1  to  4 , wherein the 16S rRNA sequence of the at least one bacterial strain in the bacterial mixture is greater than about 99.5% identical to the 16S rRNA sequence of any one of the OTUs recited in Table 5 or of any one OTU of a genus recited in Table 6. 
     
     
         6 . The pharmaceutical composition of any one of  claims 1  to  5 , wherein the 16S rRNA sequence of the at least one bacterial strain in the bacterial mixture is identical to the 16S rRNA sequence of any one of the OTUs recited in Table 5 or of any one OTU of a genus recited in Table 6. 
     
     
         7 . The pharmaceutical composition of any one of  claims 1  to  6 , wherein the at least one bacterial strain is a commensal bacterial strain. 
     
     
         8 . The pharmaceutical composition of any one of  claims 1  to  7 , wherein the at least one bacterial strain is obtained from one or more human beings. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the one or more human beings are healthy human beings and/or satisfy at least one selection criterion. 
     
     
         10 . The pharmaceutical composition of  claim 8  or  claim 9 , wherein the at least one bacterial strain is obtained from one human being. 
     
     
         11 . The pharmaceutical composition of  claim 8  or  claim 9 , wherein the at least one bacterial strain is obtained from more than one human being. 
     
     
         12 . The pharmaceutical composition of any one of  claims 1  to  11 , wherein the at least one bacterial strain is isolated and/or purified from its source material prior to forming the bacterial mixture. 
     
     
         13 . The pharmaceutical composition of any one of  claims 1  to  12 , wherein the at least one bacterial strain is cultured prior to forming the bacterial mixture. 
     
     
         14 . The pharmaceutical composition of any one of  claims 1  to  12 , wherein the at least one bacterial strain is not cultured prior to forming the bacterial mixture. 
     
     
         15 . The pharmaceutical composition of any one of  claims 1  to  11 , wherein the at least one bacterial strain is not isolated and/or purified from its source material prior to forming the bacterial mixture. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the at least one bacterial strain is not cultured prior to forming the bacterial mixture. 
     
     
         17 . The pharmaceutical composition of any one of  claims 1  to  7 , wherein the at least one bacterial strain is obtained from a laboratory stock or bacterial cell bank. 
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein the at least one bacterial strain is isolated and/or purified from its source material prior to forming the bacterial mixture. 
     
     
         19 . The pharmaceutical composition of  claim 17  or  18 , wherein the at least one bacterial strain is cultured prior to forming the bacterial mixture. 
     
     
         20 . The pharmaceutical composition of any one of  claims 1  to  19 , wherein the bacterial mixture comprises at least two bacterial strains comprising a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the bacterial mixture comprises at least about five bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the bacterial mixture comprises at least about ten bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein the bacterial mixture comprises at least about twenty bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the bacterial mixture comprises at least about thirty bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein the bacterial mixture comprises at least about forty bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein the bacterial mixture comprises at least about fifty bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         27 . The pharmaceutical composition of any one of  claims 1  to  26 , wherein the bacterial mixture comprises at least two bacterial strains, wherein each bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         28 . The pharmaceutical composition of any one of  claims 1  to  26 , wherein the bacterial mixture comprises between about five and about one hundred bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         29 . The pharmaceutical composition of  claim 28 , wherein the bacterial mixture comprises between about ten and about seventy-five bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the bacterial mixture comprises between about fifteen and about fifty bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         31 . The pharmaceutical composition of  claim 30 , wherein the bacterial mixture comprises between about twenty and about forty-five bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein the bacterial mixture comprises between about twenty-five and about forty bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         33 . The pharmaceutical composition of  claim 32 , wherein the bacterial mixture comprises between about thirty and about thirty-five bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         34 . The pharmaceutical composition of any one of  claims 1  to  21 , wherein the bacterial mixture comprises between about five and about one hundred bacterial strains in the bacterial mixture, wherein each bacterial strain comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the OTUs recited in Table 5. 
     
     
         35 . The pharmaceutical composition of any one of  claims 1  to  27 , wherein the bacterial mixture comprises a substantially complete fecal microbiota preparation from a single donor. 
     
     
         36 . The pharmaceutical composition of any one of  claims 1  to  19 , wherein the bacterial mixture comprises at least two bacterial strains comprising a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         37 . The pharmaceutical composition of  claim 36 , wherein the bacterial mixture comprises at least about five bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         38 . The pharmaceutical composition of  claim 37 , wherein the bacterial mixture comprises at least about ten bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         39 . The pharmaceutical composition of  claim 38 , wherein the bacterial mixture comprises at least about twenty bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         40 . The pharmaceutical composition of  claim 39 , wherein the bacterial mixture comprises at least about thirty bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         41 . The pharmaceutical composition of  claim 40 , wherein the bacterial mixture comprises at least about forty bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         42 . The pharmaceutical composition of  claim 41 , wherein the bacterial mixture comprises at least about fifty bacterial strains, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of one of the out of a genus recited in Table 6. 
     
     
         43 . The pharmaceutical composition of any one of  claims 1  to  19 , wherein the bacterial mixture comprises at least two bacterial strains, wherein each bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         44 . The pharmaceutical composition of any one of  claims 1  to  19 , wherein the bacterial mixture comprises between about five and about one hundred bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         45 . The pharmaceutical composition of  claim 44 , wherein the bacterial mixture comprises between about ten and about seventy-five bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         46 . The pharmaceutical composition of  claim 45 , wherein the bacterial mixture comprises between about fifteen and about fifty bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         47 . The pharmaceutical composition of  claim 46 , wherein the bacterial mixture comprises between about twenty and about forty-five bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         48 . The pharmaceutical composition of  claim 47 , wherein the bacterial mixture comprises between about twenty-five and about forty bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         49 . The pharmaceutical composition of  claim 48 , wherein the bacterial mixture comprises between about thirty and about thirty-five bacterial strains in the bacterial mixture, wherein a plurality of the bacterial strains comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         50 . The pharmaceutical composition of any one of  claims 1  to  19 , wherein the bacterial mixture comprises between about five and about one hundred bacterial strains in the bacterial mixture, wherein each bacterial strain comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of any one OTU of a genus recited in Table 6. 
     
     
         51 . The pharmaceutical composition of any one of  claims 36  to  43 , wherein the bacterial mixture comprises a substantially complete fecal microbiota preparation from a single donor. 
     
     
         52 . The pharmaceutical composition of any one of  claims 1  to  51 , wherein at least one bacterial strain is included in the bacterial mixture due to a greater amount of the bacterial strain in feces of a subject who did not develop a bloodstream infection (BSI) compared to the amount of the bacterial strain in feces of a subject who developed an BSI. 
     
     
         53 . The pharmaceutical composition of any one of  claims 1  to  51 , wherein at least one bacterial strain is included in the bacterial mixture due to a greater amount of the bacterial strain in feces of a subject receiving chemotherapy who did not develop a bloodstream infection (BSI) compared to the amount of the bacterial strain in feces of a subject receiving chemotherapy who developed an BSI. 
     
     
         54 . The pharmaceutical composition of  claim 53 , wherein the greater amount is at least two-fold greater. 
     
     
         55 . The pharmaceutical composition of any one of  claims 1  to  51 , wherein at least one bacterial strain is included in the bacterial mixture due to a greater amount of the bacterial strain in feces of a subject who did not develop a bloodstream infection (BSI) caused by a Gram negative bacteria compared to the amount of the bacterial strain in feces of a subject who developed an BSI caused by a Gram negative bacteria. 
     
     
         56 . The pharmaceutical composition of any one of  claims 1  to  55 , wherein at least one bacterial strain is included in the bacterial mixture due to its ability to help maintain and/or repair a deficient gut barrier, by directly inhibiting a pathogenic bacterium through production of a secreted product, by activating Toll-Like Receptors (TLRs), by inducing a thickening of the colonic epithelial mucus, by inducing an increase in IgA production, by inducing an increase in antimicrobial peptide production, by inducing improved tight junction integrity, by producing Short-Chain Fatty Acid (SCFAs), by enhancing production of SCFAs, by maintaining the health of colonocytes, by inducing IgA production, by increasing of butyrate levels in the gut, by inhibiting nitric oxide synthase activity, and/or by reducing the concentration of host-derived nitrate levels in the gut. 
     
     
         57 . The pharmaceutical composition of  claim 56 , wherein a plurality of bacterial strains are included in the bacterial mixture due to their ability to help maintain and/or repair a deficient gut barrier, by directly inhibiting a pathogenic bacterium through production of a secreted product, by activating Toll-Like Receptors (TLRs), by inducing a thickening of the colonic epithelial mucus, by inducing an increase in IgA production, by inducing an increase in antimicrobial peptide production, by inducing improved tight junction integrity, by producing Short-Chain Fatty Acid (SCFAs), by enhancing production of SCFAs, by maintaining the health of colonocytes, by inducing IgA production, by increasing of butyrate levels in the gut, by inhibiting nitric oxide synthase activity, and/or by reducing the concentration of host-derived nitrate levels in the gut. 
     
     
         58 . The pharmaceutical composition of  claim 56  or  claim 57 , wherein activating TLRs modulates production of antimicrobial peptides. 
     
     
         59 . The pharmaceutical composition of any one of  claims 56  to  58 , wherein the pathogenic bacterium is an antibiotic-resistant bacterium (ARB). 
     
     
         60 . The pharmaceutical composition of any one of  claims 1  to  59  further comprising a pharmaceutically acceptable excipient. 
     
     
         61 . The pharmaceutical composition of any one of  claims 1  to  60 , wherein the pharmaceutical composition is formulated for oral administration and/or for delivery of the bacterial mixture to an intestine. 
     
     
         62 . The pharmaceutical composition of  claim 61 , wherein the intestine comprises the small intestine or the large intestine. 
     
     
         63 . The pharmaceutical composition of  claim 62 , wherein the intestine comprises the small intestine and the large intestine. 
     
     
         64 . The pharmaceutical composition of  claim 62 , wherein the intestine comprises the large intestine. 
     
     
         65 . The pharmaceutical composition of any one of  claims 62  to  64 , wherein the large intestine comprises the cecum. 
     
     
         66 . The pharmaceutical composition of any one of  claims 61  to  65 , wherein delivery is substantially completed prior to the rectum. 
     
     
         67 . The pharmaceutical composition of any one of  claims 61  to  66 , wherein the pharmaceutical composition is formulated as a capsule. 
     
     
         68 . The pharmaceutical composition of  claim 67 , wherein the capsule comprises a delayed-release coating. 
     
     
         69 . The pharmaceutical composition of any one of  claims 1  to  68 , wherein a plurality of the bacterial strains in the bacterial mixture are live, vegetative cells and/or lyophilized cells. 
     
     
         70 . The pharmaceutical composition of any one of  claims 1  to  69 , wherein a plurality of the bacterial strains in the bacterial mixture are spores. 
     
     
         71 . The pharmaceutical composition of any one of  claims 1  to  70 , wherein a plurality of the bacterial strains in the bacterial mixture are non-pathogenic bacteria. 
     
     
         72 . The pharmaceutical composition of any one of  claims 1  to  71 , wherein each bacterial strain in the bacterial mixture is a non-pathogenic bacterium. 
     
     
         73 . The pharmaceutical composition of any one of  claims 1  to  72 , wherein the pharmaceutical composition is capable of maintaining and/or restoring a healthy gut barrier in a subject. 
     
     
         74 . The pharmaceutical composition of  claim 73 , wherein the subject is a human. 
     
     
         75 . The pharmaceutical composition of any one of  claims 1  to  74 , wherein at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Barnesiellaceae, at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family S24-7, at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Mogibacteriaceae, at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Christensenellaceae, at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Lachnospiraceae, and/or at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Ruminococcaceae. 
     
     
         76 . The pharmaceutical composition of  claim 75 , wherein at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Barnesiellaceae, at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family S24-7, at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Mogibacteriaceae, at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Christensenellaceae, at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Lachnospiraceae, and at least one bacterial strain in the bacterial mixture comprises a 16S rRNA sequence that is greater than about 97% identical to the 16S rRNA sequence of an OTU recited in Table 5 or Table 6 and from family Ruminococcaceae. 
     
     
         77 . A method for preventing one or more pathogenic bacteria from translocating across the gut barrier, comprising administering an effective amount of a pharmaceutical composition of any one of  claims 1  to  76  to a subject in need thereof. 
     
     
         78 . The method of  claim 77 , wherein the one or more pathogenic bacteria has not yet translocated across the gut barrier and entered the bloodstream of the subject. 
     
     
         79 . The method of  claim 77 , wherein the one or more pathogenic bacteria has translocated across the gut barrier and entered the bloodstream of the subject. 
     
     
         80 . The method of  claim 79 , wherein administering an effective amount of the pharmaceutical composition prevents further translocating of the one or more pathogenic bacterial across the gut barrier and entering the bloodstream of the subject. 
     
     
         81 . The method of any one of  claims 77  to  80 , wherein the entering the bloodstream by the one or more pathogenic bacteria causes a disease selected from a bloodstream infection (BSI); a catheter or intravascular-line infection; a liver disorder; chronic inflammation, e.g., associated with hemodialysis; a chronic inflammatory disease; cytotoxicity from chemotherapy; hypercoagulation; an infection at locations remote from the gut; inflammatory bowel disease, e.g., Ulcerative colitis and Crohn's disease; irritable bowel syndrome; a metabolic disease, e.g., insulin resistance, including Type II diabetes; another well-known antibiotic-resistant infection; rheumatoid arthritis; a urinary tract infection (UTIs), e.g., antibiotic-resistant UTIs and catheter-associated urinary tract infections; and a wound infection. 
     
     
         82 . The method of any one of  claims 77  to  81 , wherein the one or more pathogenic bacteria includes one or more of  Aeromonas hydrophila, Bacillus , e.g.,  Bacillus cereus, Bifidobacterium, Bordetella, Borrelia, Brucella, Burkholderia, C. difficile, Campylobacter , e.g.,  Campylobacter fetus  and  Campylobacter jejuni, Chlamydia, Chlamydophila, Clostridium , e.g.,  Clostridium botulinum, Clostridium difficile , and  Clostridium perfringens, Corynebacterium, Coxiella, Ehrlichia , Enterobacteriaceae, e.g., Carbapenem-resistant Enterobacteriaceae (CRE), fluoroquinolone-resistant Enterobacteriaceae, and Extended Spectrum Beta-Lactamase producing Enterobacteriaceae (ESBL-E),  Enterococcus , e.g., vancomycin-resistant  enterococcus  spp., extended spectrum beta-lactam resistant Enterococci (ESBL), and vancomycin-resistant Enterococci (VRE),  Escherichia , e.g., enteroaggregative  Escherichia coli , enterohemorrhagic  Escherichia coli , enteroinvasive  Escherichia coli , enteropathogenic  E. coli , enterotoxigenic  Escherichia coli  (such as but not limited to LT and/or ST),  Escherichia coli  0157:H7, and multi-drug resistant bacteria  E. coli, Francisella, Haemophilus, Helicobacter , e.g.,  Helicobacter pylori, Klebsiella , e.g.,  Klebsiella  pneumonia and multi-drug resistant bacteria  Klebsiella, Legionella, Leptospira, Listeria , e.g.,  Listeria monocytogenes, Morganella, Mycobacterium, Mycoplasma, Neisseria, Orientia, Plesiomonas shigelloides , Antibiotic-resistant Proteobacteria,  Proteus, Pseudomonas, Rickettsia, Salmonella , e.g.,  Salmonella  paratyphi,  Salmonella  spp., and  Salmonella typhi, Shigella , e.g.,  Shigella  spp.,  Staphylococcus , e.g.,  Staphylococcus aureus  and  Staphylococcus  spp.,  Streptococcus, Treponema, Vibrio , e.g.,  Vibrio cholerae, Vibrio parahaemolyticus, Vibrio  spp., and  Vibrio vulnificus , and  Yersinia , e.g.,  Yersinia enterocolitica.    
     
     
         83 . The method of any one of  claims 77  to  82 , wherein at least one of the one or more pathogenic bacteria is an antibiotic-resistant bacterium (ARB). 
     
     
         84 . The method of  claim 83 , wherein the ARB is Antibiotic-resistant Proteobacteria, Vancomycin Resistant  Enterococcus  (VRE), Carbapenem Resistant Enterobacteriaceae (CRE), fluoroquinolone-resistant Enterobacteriaceae, or Extended Spectrum Beta-Lactamase producing Enterobacteriaceae (ESBL-E). 
     
     
         85 . The method of any one of  claims 77  to  84 , wherein the subject in need thereof has chronic kidney disease, cancer, and/or received an organ transplant. 
     
     
         86 . The method of any one of  claims 77  to  85 , wherein the subject in need thereof is in an outpatient setting, is hospitalized, or is in long-term care facility. 
     
     
         87 . The method of any one of  claims 77  to  86 , wherein the subject in need thereof has or is at risk for a bloodstream infection (BSI); a catheter or intravascular-line infection; a liver disorder; chronic inflammation, e.g., associated with hemodialysis; a chronic inflammatory disease; meningitis; pneumonia, e.g., ventilator-associated pneumonia; skin and soft tissue infections; surgical-site infections; cytotoxicity from chemotherapy; hypercoagulation; an infection at locations remote from the gut; inflammatory bowel disease, e.g., Ulcerative colitis and Crohn's disease; irritable bowel syndrome; a metabolic disease, e.g., insulin resistance, including Type II diabetes; another well-known antibiotic-resistant infection or other well-known antibiotic sensitive infection; rheumatoid arthritis; a urinary tract infection (UTIs), e.g., antibiotic-resistant UTIs and catheter-associated urinary tract infections; and a wound infection. 
     
     
         88 . The method of any one of  claims 77  to  87 , wherein the subject in need thereof has received or is receiving, an anti-cancer therapeutic agent and/or an anti-cancer therapy. 
     
     
         89 . The method of  claim 88 , wherein the anti-cancer therapy comprises surgery, radiation therapy, chemotherapy, and/or targeted therapy. 
     
     
         90 . The method of  claim 89 , wherein the chemotherapy is a hormonal therapy or the targeted therapy is an immunotherapy. 
     
     
         91 . The method of any one of  claims 88  to  90 , wherein subject in need thereof is suffering from a side effect of the anti-cancer therapy which is caused by gut dysbiosis. 
     
     
         92 . The method of  claim 91 , wherein the bacterial mixture reduces, treats, or prevents the side effect of the anti-cancer therapeutic agent and/or the side effect of the anti-cancer therapy. 
     
     
         93 . A method of increasing efficacy of an anti-cancer therapeutic agent and/or anti-cancer therapy comprising administering an effective amount of a pharmaceutical composition of any one of  claims 1  to  76  to a subject in need thereof. 
     
     
         94 . The method of  claim 93 , wherein the anti-cancer therapy comprises surgery, radiation therapy, chemotherapy, and/or targeted therapy. 
     
     
         95 . The method of  claim 93  or  claim 94 , wherein the pharmaceutical composition is administered after of the anti-cancer therapeutic agent and/or the anti-cancer therapy. 
     
     
         96 . The method of  claim 93  or  claim 94 , wherein the pharmaceutical composition is administered before of the anti-cancer therapeutic agent and/or the anti-cancer therapy. 
     
     
         97 . The method of  claim 93  or  claim 94 , wherein the pharmaceutical composition is administered contemporaneously with the anti-cancer therapeutic agent and/or the anti-cancer therapy. 
     
     
         98 . The method of claim any one of  claims 94  to  97 , wherein the anti-cancer therapy is a targeted therapy directed to a checkpoint molecule and the subject is refractory and/or non-responsive to the treatment directed to the checkpoint molecule. 
     
     
         99 . The method of  claim 98 , wherein the treatment directed to the checkpoint molecule comprises administration of Keytruda (Pembrolizumab), Opdivo (Nivolumab), Yervoy (Ipilimumab), Tecentriq (atezolizumab), Bavencio (avelumab), or Imfinzi (durvalumab).