Precision Microbiome Reconstitution Restores Bile Acid Mediated Resistance to Clostridium Difficile

Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, No D, Liu H, Kinnebrew M, Viale A, Littmann E, van den Brink MR, Jenq RR, Taur Y, Sander C, Cross J, Toussaint NC, Xavier JB, Pamer EG.

Nature. 2014 Oct 22. doi: 10.1038/nature13828.

Pamer-Buffie-Xavier Photo

Pictured Left to Right: Eric Pamer, Charlie Buffie, and Joao Xavier

The mammalian gastrointestinal tract is colonized by hundreds of microbial species that provide colonization resistance against intestinal pathogens. Clostridium difficile is a major cause of diarrhea and occurs in individuals following antibiotic treatment, suggesting that loss of normal, commensal bacterial populations renders individuals susceptible to this infection.  Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms has remained unclear. Charlie Buffie, working with Joao Xavier and Eric Pamer at Memorial Sloan Kettering Cancer Center (MSKCC), correlated loss of specific bacterial taxa with development of C. difficile infection, by treating mice with different antibiotics that result in distinct microbiota changes and lead to varied susceptibility to C. difficile. Mathematical modelling augmented by analyses of the microbiota of hospitalized patients identified resistance-associated bacteria common to mice and humans. Using these platforms, the MSKCC team determined that Clostridium scindens, a bile acid 7α-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, confers resistance by promoting the production of secondary bile acids. These findings have implications for the rational design of targeted antimicrobials as well as microbiome-based diagnostics and therapeutics for individuals at risk of C. difficile infection. Pubmed: 25337874