To investigate the link between antibiotic treatment and susceptibility to intestinal Clostridium difficile infection (CDI), Buffie et al. treated mice with different antibiotics and correlated the observed differences in intestinal bacterial composition with susceptibility to CDI. This analysis revealed that the presence of Clostridium scindens was indicative of resistance to CDI, and adoptive transfer of this bacterium was sufficient to increase resistance to CDI. Notably, the presence of C. scindens also correlated with resistance to CDI in patients undergoing allogeneic haematopoietic stem-cell transplantation, who display alterations in their gut microbiome as a result of chemo- and radiotherapy and antibiotic usage during transplantation. C. scindens-mediated resistance was associated with the expression of operons involved in secondary bile acid biosynthesis and was dependent on the presence of bile in the intestine, suggesting that C. scindens uses host-derived bile to synthesize compounds that inhibit C. difficile growth.