Fecal microbiota transplantation efficacy for Clostridium difficile infection: A trans-kingdom battle between donor and recipient gut microbiomes

Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridium difficile infections (rCDI) and other dysbiosis-related conditions. In a single cohort study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT) as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning methods, our results suggested that the FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes, both at the taxonomical and functional levels. Importantly, we observed that the presence of specific bacteria in donors (Clostridiodes spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of specific fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could accurately predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut microbial ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers. Therefore, a better understanding of such mechanisms can be fundamental key elements to develop adaptive, personalized microbial-based strategies for the restoration of the gut ecosystem.