Methods and compositions for reducing clostridium difficile infection
Inventors
Pamer, Eric • Buffie, Charlie • McKenney, Peter
Assignees
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Publication Number
US-12414969-B2
Publication Date
2025-09-16
Expiration Date
Abstract
The present invention relates to methods and compositions for reducing the risk and severity of C. difficile infection. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacterium Clostridium scindens, contributes substantially to resistance against C. difficile infection. Without being bound by any particular theory, it is believed that this is achieved through the biosynthesis of secondary bile acids.
Core Innovation
The described invention relates to methods and compositions to reduce Clostridium difficile infection risk or severity by restoring gut colonization resistance through secondary bile acid biosynthesis. The approach centers on bile acid-inducible (bai) 7α/β-dehydroxylation operon activity, including baiCD/7α-hydroxysteroid dehydrogenase, which converts primary bile acids into secondary bile acids.
Production of secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA) is associated with resistance to C. difficile. The document describes bacterial contributors to this secondary bile acid pathway, including Clostridium scindens and additional Clostridia, and describes secondary bile acid biosynthesis gene family concepts including bai operon/nucleic acid.
The invention further includes compositions and diagnostic concepts. Compositions include recombinant cells, isolated or probiotic bacterial strains, multi-bacteria consortia, enzymes, and/or secondary bile acids, and the document reports formulations containing C. scindens with Blautia hansenii and/or Barnesiella intestihominis. Diagnostic concepts include assessing levels of resistance-associated bile acid-converting bacteria, 7α-hydroxysteroid dehydrogenase activity, or bai operon nucleic acid in fecal samples, including kits.
Claims Coverage
The partial claim set provided includes one independent claim. The independent claim covers a multi-bacterial capsule formulation with defined bacteria and a secondary bile acid, together with functional bile-acid-to-secondary-bile-acid conversion in a subject.
Multi-bacterial capsule with C. scindens and bile acid conversion capability
A composition formulated for administration to a subject in a capsule, comprising two or more purified or isolated bacteria or spores thereof including Clostridium scindens and either Blautia hansenii or Barnesiella intestihominis, wherein at least one of the bacteria or spores is capable of converting a primary bile acid to a secondary bile acid.
Secondary bile acid component selected from deoxycholic acid and lithocholic acid
The composition further comprises a secondary bile acid selected from deoxycholic acid, lithocholic acid, or a combination thereof.
Overall, the independent claim coverage is directed to a capsule formulation containing purified or isolated bacteria or spores including C. scindens plus Blautia hansenii and/or Barnesiella intestihominis, with an included secondary bile acid and with at least one component capable of converting a primary bile acid to a secondary bile acid.
Stated Advantages
Reduce risk of Clostridium difficile-associated disease during antibiotic therapy.
Inhibit proliferation.
Reduce severity and specific symptoms, including defined symptom sets.
Documented Applications
A formulation for administration to a subject in a context of antibiotic therapy to reduce risk of developing Clostridium difficile-associated disease.
Diagnostic concepts based on levels of resistance-associated bile acid-converting bacteria, 7α-hydroxysteroid dehydrogenase activity, or bai operon nucleic acid in fecal samples, including kits.
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