Compositions and methods comprising a defined microbiome and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10058576-B2
Application number	US-201615090609-A
Country	US
Kind code	B2
Filing date	Apr 4, 2016
Priority date	Oct 3, 2013
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

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.

First claim

What is claimed is:

1. A method for altering gut microbiota to reduce urease gene content or activity via reducing or eliminating urease producing bacteria from the gut in order to reduce ammonia production therefrom, in a subject in need thereof, the method comprising;
a) administering to the subject 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, wherein one or more antibiotics is administered for at least about 48, 72, or 96 hours prior to the administration of a composition comprising Paraprevotella clara, Bifidobacterium longum, Collinsella aerofaciens, Coprococcus comes, Dorea longicatena, Bacteroides eggerthii str ., and Bacteroides vulgates bacteria, said bacteria having no urease gene content or urease activity;
b) administering said composition to the subject, under conditions wherein said bacteria colonize and populate the gut, thereby reducing urease gene content, or activity or both in gut microbiota and ammonia production in the gut of the subject.

2. The method of claim 1 , wherein said subject is a human and has a disease associated with an undesirable gut microbiome, said composition alleviating symptoms associated with said undesirable gut microbiome, wherein said administration of said 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 and the composition further comprises one or more of Clostridium sp., Lactobacillus sp., Lactobacillus murinus, Mucispirillum schaedleri, Eubacterium plexicaudatum, Firmicutes bacterium, Clostridium sp., and Parabacteroides sp.

3. The method of claim 1 , comprising administering an effective amount of a purgative agent to the subject between steps a) and b), thereby purging the intestines of said subject prior to administration of said composition.

4. The method of claim 3 , wherein said subject is administered antibiotics and a purging agent prior to administration of said composition, said antibiotic being one or both of neomycin and vancomycin, and said purging agent being administered for at least about 12-36 hours prior to the administration of the composition.

5. The method of claim 3 , wherein said purgative agent is selected from the group consisting of polyethene glycol (PEG), magnesium citrate, sodium picosulphate plus magnesium citrate, PEG plus ascorbic acid, and sodium phosphate.

6. The method of claim 1 , wherein said composition comprises one or more additional bacteria belonging to a genus selected from the group consisting of Bifidobacterium, Bacteroides, Tannerella, Parabacteroides, Bacillus, Lactobacillus, Anaerostipes, Blautia, Coprococcus, Dorea, Clostridium XI, Collinsella , and Paraprevotella.

7. The method of claim 2 , wherein the disease is a metabolic disorder selected from the group consisting of Hyperammonemia, and Transient Hyperammonemia of the Newborn.

8. The method of claim 2 , wherein the disease is Clostridium difficile colitis, inflammatory bowel disease, cirrhosis, or hepatic encephalopathy.

9. The method of claim 1 or claim 2 , wherein the level of bacteria repopulating the gut is monitored by assessing a parameter selected from the group consisting of 16S rRNA copy number, 16S rRNA gene sequencing, fecal urease levels, fecal or circulating amino acids, biogenic amines, fecal ammonia levels, and circulating ammonia levels.

Assignees

• Univ Pennsylvania

Inventors

• Bushman Frederic
• Wu Gary
• Lewis James
• Goulian Mark

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K35/745

  Bifidobacteria · CPC title

• C12N1/20

  Bacteria; Culture media therefor · CPC title

• A61K35/744

  Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs · CPC title

• A61K35/742

  Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes · CPC title