Probiotic compositions containing clostridiales for inhibiting inflammation

Abstract

Pharmaceutical compositions containing microbial entities are described herein. The pharmaceutical compositions may optionally contain or be used in conjunction with one or more prebiotics. Uses of the pharmaceutical compositions to treat or prevent disorders of the local or systemic microbiome in a subject are also provided.

1 . A pharmaceutical composition comprising an isolated population of anti-inflammatory bacterial cells of the order Clostridiales capable of decreasing the secretion of a pro-inflammatory cytokine and/or increasing the secretion of an anti-inflammatory cytokine by a population of human peripheral blood mononuclear cells (PBMCs), and a pharmaceutically acceptable excipient. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the secretion of a pro-inflammatory cytokine by a population of PBMCs is induced by  Enterococcus faecalis.    
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the anti-inflammatory bacterial cells are of the family Lachnospiraceae. 
     
     
         4 . The method of  claim 1 , wherein the anti-inflammatory bacterial cells are of the genus  Blautia, Clostridium, Eubacterium,  or  Ruminococcus.    
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the anti-inflammatory bacterial cells are of the genus  Blautia.    
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the anti-inflammatory bacterial cells are of a species selected from the group consisting of  Blautia coccoides, Blautia faecis, Blautia glucerasea, Blautia hansenii, Blautia hyrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia schinkii, Blautia  sp. M25,  Blautia stercoris, Blautia wexlerae, Blautia  uncultured  bacterium  clone BKLE_a03_2,  Blautia  uncultured  bacterium  clone SJTU_B_14_30,  Blautia  uncultured  bacterium  clone SJTU_C_14_16,  Blautia  uncultured  bacterium  clone S1-5, and  Blautia  uncultured PAC000178_s. 
     
     
         7 . The pharmaceutical composition of  claim 4 , wherein the anti-inflammatory bacterial cells are of the species  Ruminococcus gnavus  or  Eubacterium rectale.    
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the anti-inflammatory bacterial cells comprise a bacterial cell in vegetative form or in spore form. 
     
     
         9 . (canceled) 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the isolated population of anti-inflammatory bacterial cells further comprises a bacterial cell belonging to a bacterial strain set forth in Table 1, Table 1A, Table 1B, Table 1C, Table 1D, Table 1E, or Table 1F. 
     
     
         11 - 13 . (canceled) 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the pro-inflammatory cytokine is selected from the group consisting of IFNγ, IL-12p′70, IL-1α, IL-6, IL-8, MCP1, MIP 1 α, MIP1β, TNFα, and combinations thereof. 
     
     
         15 . The pharmaceutical composition of  claim 1 , wherein the anti-inflammatory cytokine is selected from the group consisting of IL-10, IL-13, IL-4, IL-5, TGFβ, and combinations thereof. 
     
     
         16 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for oral administration or rectal administration. 
     
     
         17 . (canceled) 
     
     
         18 . The pharmaceutical composition of  claim 1 , wherein the anti-inflammatory bacterial cells decrease the secretion of a pro-inflammatory cytokine and/or increase the secretion of an anti-inflammatory cytokine by a population of human peripheral blood mononuclear cells (PBMCs) in vitro. 
     
     
         19 . A method for reducing inflammation in a subject, the method comprising administering the pharmaceutical composition of  claim 1  to the subject, thereby reducing inflammation in the subject. 
     
     
         20 . The method of  claim 19 , wherein the subject has an autoimmune or inflammatory disorder. 
     
     
         21 . The method of  claim 20 , wherein the autoimmune or inflammatory disorder is selected from the group consisting of graft-versus-host disease (GVHD), an inflammatory bowel disease (IBD), ulterative colitis, Crohn's disease, multiple sclerosis (MS), systemic lupus erythematosus (SLE), type I diabetes, rheumatoid arthritis, Sjögren's syndrome, and Celiac disease. 
     
     
         22 . The method of  claim 19 , wherein the pharmaceutical composition is administered orally or rectally. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 19 , wherein administration of the pharmaceutical composition reduces inflammation in the gastrointestinal tract of the subject. 
     
     
         25 . The method of  claim 19 , wherein administration of the pharmaceutical composition reduces inflammation at a site distal to the gastrointestinal tract of the subject. 
     
     
         26 . The method of  claim 19 , wherein the subject has a dysbiosis. 
     
     
         27 . The method of  claim 26 , wherein the dysbiosis is a gastrointestinal dysbiosis. 
     
     
         28 . The method of  claim 26 , wherein the dysbiosis is a distal dysbiosis. 
     
     
         29 . The method of  claim 19 , wherein the anti-inflammatory bacterial cells of the pharmaceutical composition engraft in the gastrointestinal tract of the subject. 
     
     
         30 . (canceled)