Data associated with "Personalized Clostridioides difficile engraftment risk prediction and probiotic therapy assessment in the human gut"

Clostridioides difficile colonizes up to 30-40% of community-dwelling adults without causing disease. C. difficile infections (CDIs) are the leading cause of antibiotic-associated diarrhea in the U.S. and typically develop in pre-colonized individuals following disruption of the gut microbiota due to antibiotic or chemotherapy treatments. Further treatment of CDI with antibiotics is not always effective and can lead to antibiotic resistance and recurrent infections (rCDI). The most effective treatment for rCDI is the reestablishment of an intact microbiota via fecal microbiota transplants (FMTs). However, the success of FMTs has been difficult to generalize to other diseases because the microbial interactions that prevent colonization and facilitate the successful clearance of C. difficile are still only partially understood. Here we show how microbial community-scale metabolic models (MCMMs) accurately predicted known instances of C. difficile colonization susceptibility or resistance in vitro and in vivo. MCMMs provide detailed mechanistic insights into the ecological interactions that govern C. difficile colonization, like cross-feeding or competition involving metabolites like succinate, trehalose, and ornithine, which differ from person to person. Indeed, three distinct C. difficile metabolic niches emerge from our MCMMs, two associated with growth and one that represents non-growth, which are consistently observed across 15,204 individuals from five independent cohorts. Finally, we show how MCMMs can predict personalized colonization and C. difficile growth suppression for an existing probiotic cocktail (6 of 8 VE303 strains) designed to replace FMTs for the treatment rCDI, and we identify new probiotic targets for future validation. Overall, this powerful modeling approach predicts personalized C. difficile colonization risk and with further validation may be useful in assessing probiotic treatment efficacy. MCMMs could be extended to understand the mechanistic underpinnings of personalized colonization of other opportunistic bacterial pathogens, beneficial probiotic organisms, or more complex microbial consortia.