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Inter-individual Recovery of the Microbiota and Metabolome Over Time Following Fecal Microbiota Transplantation in Patients with Recurrent Clostridium difficile Infection

A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery, a critical component of disease recovery. However, identification of the specific microbes and their functions that directly impact recovery from CDI remains difficult. We assessed for associations among microbial community members and metabolites in patients with recurrent CDI following treatment with FMT over time to identify groups of bacteria with potential restorative functions. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Increased levels of the secondary bile acid deoxycholic acid and the short chain fatty acids (SCFAs) butyrate, acetate, and propionate were observed post-FMT. To take into account longitudinal sampling and intra-individual differences, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Microbial metabolites that were increased following FMT associated with members classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT. IMPORTANCE Clostridium difficile infection (CDI) is an urgent and serious healthcare-associated problem. In recent years, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent CDI, a frequent outcome of disease. While it is apparent that FMT promotes recovery of the microbiota, it is unclear how microbes and their functions promote recovery from disease. This study aimed to identify associations among microbes and metabolites following FMT and to identify critical microbial functions following FMT treatment for recurrent CDI. Overall, recovery of the metabolome was highly dynamic and individualized in all patients, who were all successfully treated. Our results suggest that microbial changes following FMT may be highly specific to the donor-recipient relationship. Further understanding of the host-microbe environments necessary to enable successful transplantation of microbes during FMT could aid development of specific microbial therapeutics for recurrent CDI and other gastrointestinal diseases.