Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile

A fraction of the intestinal microbiota as precise as a single bacterial species confers infection resistance by synthesizing Clostridium difficile -inhibiting metabolites from host-derived bile salts. Gut bacteria providing resistance to Clostridium difficile Antibiotic treatment can kill many members of the normal commensal gut microbiota, leaving patients susceptible to intestinal infection. Among infections that can result from antibiotic-mediated commensal flora destruction, Clostridium difficile colitis is one of the most common and difficult to treat. Eric Pamer and colleagues screened the mouse microbiota with a panel of antibiotics and looked for distinct microbiota changes associated with susceptibility to C. difficile . They identified resistance-associated microbiota constituents common to mice and humans, including Clostridium scindens , which they show confers resistance to infection by synthesizing C. difficile -inhibiting metabolites from host-derived bile salts. These findings could point the way towards novel approaches to the treatment and prevention of C. difficile colitis such as replenishment of secondary bile acids or biosynthesis-competent bacteria as adjuncts to faecal microbiota transplants. The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens 1 . Many antibiotics destroy intestinal microbial communities and increase susceptibility to intestinal pathogens 2 . Among these, Clostridium difficile , a major cause of antibiotic-induced diarrhoea, greatly increases morbidity and mortality in hospitalized patients 3 . Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms remain unclear. Here we correlate loss of specific bacterial taxa with development of 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 identifies resistance-associated bacteria common to mice and humans. Using these platforms, we determine that Clostridium scindens , a bile acid 7α-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, enhances resistance to infection in a secondary bile acid dependent fashion. Using a workflow involving mouse m