COMPOSITIONS AND METHODS FOR TREATING HEPATIC ENCEPHALOPATHY
Provided herein are methods and compositions for treating and/or preventing hepatic encephalopathy involving administering to a subject a pharmaceutical composition comprising a purified bacterial mixture.
1 . A method of treating or preventing hepatic encephalopathy in a subject comprising administering to the subject a pharmaceutical composition comprising a purified bacterial mixture comprising bacterial strains selected from the group consisting of Clostridium bolteae, Anaerotruncus colihominis , Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Clostridium innocuum , and Flavonifractor plautii.
2 . The method of claim 1 , wherein the pharmaceutical composition comprises a purified bacterial mixture consisting of Clostridium bolteae, Anaerotruncus colihominis , Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Clostridium innocuum , and Flavonifractor plautii.
3 . A method of treating or preventing hepatic encephalopathy in a subject comprising administering to the subject a pharmaceutical composition comprising a purified bacterial mixture comprising bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity with the nucleic acid sequences selected from the group consisting of SEQ ID NOs: 1-8.
4 . The method of claim 3 , wherein the pharmaceutical composition comprises a purified bacterial mixture consisting of bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity with the nucleic acid sequences selected from the group consisting of SEQ ID NOs: 1-8.
5 . The method of any one of claims 1 - 4 , wherein the subject has or is risk for liver cirrhosis.
6 . The method of any one of claims 1 - 5 , wherein one or more of the bacterial strains are spore-formers.
7 . The method of any one of claims 1 - 6 , wherein the bacterial strains originate from more than one human donor.
8 . The method of any one of claims 1 - 7 , further comprising a pharmaceutically acceptable excipient.
9 . The method of any one of claims 1 - 8 , wherein the bacterial strains are lyophilized.
10 . The method of any one of claims 1 - 8 , wherein the bacterial strains are spray-dried.
11 . The method of any one of claims 1 - 10 , wherein one or more of the bacterial strains are in spore form.
12 . The method of any one of claims 1 - 11 , wherein each of the bacterial strains is in spore form.
13 . The method of any one of claims 1 - 11 , wherein one or more of the bacterial strains are in vegetative form.
14 . The method of any one of claim 1 - 10 or 13 , wherein each of the bacterial strains is in vegetative form.
15 . The method of any one of claims 1 - 14 , wherein the pharmaceutical composition further comprises one or more enteric polymers.
16 . The method of any one of claims 1 - 15 , wherein the pharmaceutical composition comprises between 1×10 7 and 1×10 10 colony forming units (CFUs) per bacterial strain.
17 . The method of any one of claims 1 - 16 , wherein the pharmaceutical composition is formulated for oral administration.
18 . The method of any one of claims 1 - 17 , wherein the pharmaceutical composition is in the form of a capsule.
19 . The method of any one of claims 1 - 18 , wherein the pharmaceutical composition is formulated for delivery to the colon.
20 . The method of any one of claims 1 - 19 , wherein the subject is administered one or more doses of an antibiotic prior to the pharmaceutical composition.
21 . The method of any one of claims 1 - 20 , wherein the subject is human.
22 . The method of any one of claims 1 - 21 , wherein the pharmaceutical composition is administered as one dose.
23 . The method of any one of claims 1 - 21 , wherein the pharmaceutical composition is administered to the subject more than once.
24 . The method of any one of claim 1 - 21 or 23 , wherein the pharmaceutical composition is administered as multiple doses.