Methods and compositions for reducing vancomycin-resistant
The present invention relates to methods and compositions for reducing the risk and severity of vancomycin-resistant Enterococci infection or colonization. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacteria Clostridium scindens and/or the bacteria Blautia producta contribute substantially to resistance against vancomycin-resistant Enterococci infection or colonization. Without being bound by any particular theory, it is believed that this is achieved through the biosynthesis of secondary bile acids in the case of Clostridium scindens.
1. A method for reducing the risk of vancomycin-resistant Enterococci (VRE) infection or VRE colonization in a subject, and/or increasing resistance to VRE infection or VRE colonization in the subject, and/or reducing the severity of VRE infection in the subject, and/or reducing the amount of VRE colonizing the subject, comprising administering, to the subject in need of such treatment, a therapeutically effective amount of a composition comprising a Clostridiales VE202-05 bacteria and at least one of a Clostridium scindens bacteria and/or a Blautia producta bacteria, wherein the composition is administered to the subject by a gastrointestinal administration.
2. The method of claim 1 , wherein the composition comprises both the Clostridium scindens bacteria and the Blautia producta bacteria.
3. The method of claim 1 , wherein the composition further comprises one or more additional species of bacteria selected from the group consisting of a member of the Bacteroidetes phylum and a member of the Firmicutes phylum.
4. The method of claim 3 , wherein the additional species of bacteria that is a member of the Firmicutes phylum is a member of the Lachnospiraceae family.
5. The method of claim 1 , wherein the composition further comprises one or more additional species of bacteria selected from the group consisting of a Barnesiella intestihominis, Blautia hansenii, Pseudoflavonifractor capillosus, Clostridium hiranonis, Clostridium hylemonae, Clostridium perfringens, Clostridium sordellii, Proteocatella sphenisci , Lachnospiraceae 5_1_57FAA, and Clostridiales VE202-26.
6. The method of claim 1 , wherein the composition comprises the Clostridium scindens bacteria and further comprises a Blautia hansenii bacteria.
7. The method of claim 1 , wherein the composition comprises the Blautia producta bacteria and further comprises a Clostridium bolteae bacteria.
8. The method of claim 1 , wherein the composition further comprises one or more additional species of bacteria selected from the group consisting of Parabacteroides distasonis, Bacteroides sartorii, Clostridium innocuum, Akkermansia muciniphila, Clostridium bolteae , and Eubacterium dolichum.
9. The method of claim 1 , wherein one or more of the bacteria are recombinant bacteria which express a recombinant enzyme that can convert a primary bile acid to a secondary bile acid, synthesize a recombinant antibiotic resistance molecule, express a recombinant protease, or express a recombinant glycosidase.
10. The method of claim 9 , wherein the recombinant enzyme that can convert a primary bile acid to a secondary bile acid is a bile acid hydroxysterol dehydrogenase enzyme.
11. The method of claim 1 , further comprising administering the bacteria as isolated viable bacteria.
12. The method of claim 1 , further comprising administering the bacteria as isolated spores thereof.
13. The method of claim 1 , wherein the gastrointestinal administration is oral, nasogastric, or rectal administration.
14. The method of claim 13 , wherein the composition further comprises a probiotic bacteria, a probiotic yeast, or a combination thereof.
15. The method of claim 13 , wherein the composition is a liquid, a suspension, a dried powder, a tablet, a capsule, or a food product.
16. The method of claim 1 , further comprising administering to the subject, an antibiotic, an anti-toxin antibody, an herbal remedy, a probiotic bacteria, a probiotic yeast, or a combination thereof.
17. The method of claim 1 , wherein the therapeutically effective amount ameliorates at least one symptom of VRE infection selected from the group consisting of abdominal tenderness, abdominal pain, abdominal cramping, sepsis, endocarditis, meningitis, headache, stiff neck, confusion, back pain, pneumonia, fever, chills, diarrhea, urinary tract infection, endocarditis, elevated white blood cell count, and decreased serum albumin.
18. The method of claim 1 , wherein the therapeutically effective amount inhibits proliferation of VRE in the gastrointestinal tract of the subject.
19. The method of claim 1 , further comprising detecting a VRE-specific 16S rRNA in a sample from the subject.