ABSTRACT
Colonization resistance provided by the gut microbiota is essential for resisting both initial Clostridioides difficile infection (CDI) and potential recurrent infection (rCDI). Although fecal microbiota transplantation (FMT) has been successful in treating rCDI by restoring microbial composition and function, mechanisms underlying the efficacy of standardized stool-derived products remain poorly understood.
Using a combination of 16S rRNA gene-based and metagenomic sequencing alongside metabolomics, we investigated microbiome recovery following FMT from human and murine donor sources in a mouse model of rCDI. We found that a human-derived microbiota was less effective in clearing C. difficile compared to a mouse-derived microbiota, despite recovery of taxonomic diversity, compositional changes, and bacterial functions typically associated with clearance. Metabolomic analysis revealed deficits in secondary metabolites compared to those that received murine FMT, suggesting a functional remodeling between human microbes in their new host environment.
Collectively, our data revealed additional environmental, ecological, or host factors to consider in FMT-based recovery from rCDI.
