Host origin of microbiota drives functional recovery and <i>Clostridioides difficile</i> clearance in mice

<i>Clostridioides difficile</i> is a significant healthcare-associated pathogen, with recurrent infections presenting a major treatment challenge due to further disruption of the microbiota after antibiotic administration. Despite the success of fecal microbiota transplantation (FMT) for the treatment of recurrent infection, the mechanisms mediating its efficacy remain underexplored. This study reveals that the effectiveness of FMT may be compromised by a mismatch between donor microbes and the recipient environment, leading to deficits in key microbial metabolites. These findings highlight additional factors to consider when assessing the efficacy of microbial-based therapeutics for <i>C. difficile</i> infection (CDI) and other conditions.