Compositions and Methods Comprising a Defined Microbiome and Methods of Use Thereof

Abstract

The invention features the use of a defined microbial consortia for the replacement of a gut microbiome associated with disease. In particular, the invention provides for the treatment of hyperammonemia, Clostridium difficile colitis, hepatic encephalopathy associated with cirrhosis, and inflammatory bowel disease.

1 .- 32 . (canceled) 
     
     
         33 . A method for treating or preventing symptoms of inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a composition comprising an effective amount of at least one urease negative Gammaproteobacteria. 
     
     
         34 . The method of  claim 33 , further comprising administering to the subject, prior to administration of the composition, an effective amount of one or more antibiotics sufficient to reduce the population of bacteria in the gut microbiota to a level suitable for repopulation of newly introduced bacteria. 
     
     
         35 . The method of  claim 34 , wherein the one or more antibiotics is administered for at least about 48, 72, or 96 hours prior to the administration of the composition. 
     
     
         36 . The method of  claim 33 , further comprising administering to the subject prior to administration of the composition, an effective amount of a purgative agent to the subject, thereby purging the intestines of the subject prior to administration of the composition. 
     
     
         37 . The method of  claim 36 , wherein the purgative agent is administered at least about 12-36 hours prior to the administration of the composition. 
     
     
         38 . The method of  claim 33 , wherein said bacteria colonize and populate the gut, thereby reducing urease gene content, or activity or both in the gut microbiota and ammonia production in the gut of the subject, thereby treating or preventing the symptoms of IBD. 
     
     
         39 . The method of  claim 38 , wherein the bacteria colonize and populate the sigmoid colon. 
     
     
         40 . The method of  claim 33 , wherein said at least one Gammaproteobacteria is Enterobacteriaceae shigella. 
     
     
         41 . The method of  claim 33 , further comprising administration of at least one additional urease negative bacteria belonging to a genus selected from the group consisting of  Bifidobacterium, Bacteroides, Tannerella, Parabacteriodes, Bacillus, Lactobacillus, Anaerostipes, Blauta, Coprococcus, Dorea, Clostridium  XI,  Collinsella , and  Paraprevotella.    
     
     
         42 . The method of  claim 33 , wherein the administration of the composition is via a route selected from the group consisting of by endoscopy, by enteroscopy, by colonoscopy, a nasoduodenal catheter, an enema, and orally in a consumable capsule or pill. 
     
     
         43 . The method of claim  28 , wherein the bacteria is lyophilized and administered orally in a consumable capsule or pill. 
     
     
         44 . A method for preparing a defined microbial consortia composition for treating or preventing symptoms of inflammatory bowel disease (IBD) in a subject in need thereof, the process comprising;
 a) preparing a liquid culture of bacteria cells comprising at least one urease negative Gammaproteobacteria;   b) harvesting said cells after a suitable period of growth;   c) resuspending said cells in a lyophilization medium, said medium optionally comprising cyroprotectorants, biological or chemical oxygen scavengers;   d) transferring said resuspended cells into a lyophilizer under anaerobic conditions and lyophilizing the cells'   e) packaging said lyophilized cells into a capsule or pill under oxygen free conditions; and   f) optionally packaging said capsules or pill into glass ampoules to maintain anaerobic conditions during shipment and storage.   
     
     
         45 . A capsule comprising the bacteria produced by the process of  claim 44 .