Methods and compositions for reducing clostridium difficile infection

A method for reducing the risk of Clostridium difficile infection in a subject, reducing the severity of Clostridium difficile infection in a subject, decreasing the amount of Clostridium difficile toxin in a subject, increasing resistance to Clostridium difficile infection in a subject, reducing risk of developing Clostridium difficile-associated disease in a subject, treating Clostridium difficile-associated disease in a subject, preventing a Clostridium difficile-associated disease in a subject, or decreasing the severity of one or more symptoms of an intestinal disorder in a subject, comprising administering, to a subject in need of such treatment,

• (i) an effective amount of a composition comprising two or more isolated bacteria or spores thereof, selected from the group consisting of Clostridium scindens, Clostridium hiranonis, Clostridium hylemonae, Clostridium perfringens, Clostridium sordellii, Proteocatella sphenisci, Lachnospiraceae 5_1_57FAA, Clostridiales VE202-05, Clostridiales VE202-26, Barnesiella intestihominis, Blautia hansenii, Pseudoflavonifractor capillosus, and combinations thereof, wherein the two or more isolated bacteria or spores thereof are in a formulation for administration to a subject;
• (ii) an effective amount of a recombinant cell expressing a bile acid-inducible (bai) 7α/β-dehydroxylation operon, wherein the recombinant cell comprises one or more exogenous nucleic acids encoding a bile acid-inducible (bai) 7α/β-dehydroxylation operon, wherein the one or more exogenous nucleic acids are operably linked to a promoter;
• or
• (iii) an effective amount of an agent selected from the group consisting of an enzyme that converts a bile acid to a secondary bile acid, a secondary bile acid, deoxycholic acid, lithocholic acid, purified bacteria or spores thereof expressing an enzyme that converts a bile acid to a secondary bile acid, and combinations thereof.

A method of diagnosing a subject with a Clostridium difficile infection, or at risk for Clostridium difficile infection, comprising

• (i) obtaining an intestinal microbiota sample from a subject and determining the level of one or more bacterium present in the intestinal microbiota sample that can convert a primary bile acid to a secondary bile acid;
• comparing the level of the one or more bacterium in the sample with a reference bacterium level;
• and
• diagnosing the subject as having a Clostridium difficile infection, or at risk for Clostridium difficile infection, when the level of the one or more bacterium in the sample is lower than the bacterium reference level;
• (ii) obtaining an intestinal microbiota sample from a subject and determining the activity or level of 7α-hydroxysteroid dehydrogenase enzyme present in the intestinal microbiota sample;
• comparing the activity or level of 7α-hydroxysteroid dehydrogenase enzyme in the sample with a reference 7α-hydroxysteroid dehydrogenase enzyme activity or level;
• and
• diagnosing the subject as having a Clostridium difficile infection, or at risk for Clostridium difficile infection, when the activity or level of 7α-hydroxysteroid dehydrogenase enzyme in the sample is lower than the reference 7α-hydroxysteroid dehydrogenase enzyme activity or level;
• or
• (iii) obtaining an intestinal microbiota sample from a subject and quantifying the level of bile acid-inducible (bai) 7α/β-dehydroxylation operon nucleic acid present in the intestinal microbiota sample;
• comparing the level of bile acid-inducible (bai) 7α/β-dehydroxylation operon nucleic acid present in the intestinal microbiota sample with a reference bile acid-inducible (bai) 7α/β-dehydroxylation operon nucleic acid level;
• and
• diagnosing the subject as having a Clostridium difficile infection, or at risk for Clostridium difficile infection, when the level of bile acid-inducible (bai) 7α/β-dehydroxylation operon nucleic acid present in the intestinal microbiota sample is lower than the reference level.