Temporal Gut Microbial Changes Predict RecurrentClostridium difficilein Patients with and without Ulcerative Colitis

ABSTRACT Background Ulcerative colitis (UC) carries an increased risk of primary and recurrent Clostridium difficile infection (rCDI) and CDI is associated with UC flares. We hypothesized that specific fecal microbial changes associate with UC flare and rCDI. Methods We conducted a prospective observational cohort study of 57 patients with UC and CDI, CDI only, and UC flare only. Stool samples were collected at baseline, at the end of antibiotic therapy, and after reconstitution for 16S rRNA sequencing. The primary outcomes were recurrent UC flare and rCDI. Logistic regression and Lasso models were constructed for analysis. Results There were 21 (45.7%) patients with rCDI, while 11 (34.4%) developed UC flare. Patients with rCDI demonstrated significant inter-individual ( P =.008) and intra-individual differences ( P =.004 relative to baseline samples) in community structure by Jensen-Shannon distance (JSD) compared with non-rCDI. Two cross-validated models identified by Lasso regression predicted risk of rCDI: a baseline model with female gender, hospitalization for UC in the past year, increased Ruminococcaceae and Verrucomicrobia, and decreased Eubacteriaceae, Enterobacteriaceae, Lachnospiraceae, and Veillonellaceae (AuROC=0.94); and a model 14 days after completion of antibiotics with female gender, increased Shannon diversity, Ruminococcaceae and Enterobacteriaceae, and decreased community richness and Faecalibacterium (AuROC=0.9). Adding JSD between baseline and post-treatment samples to the latter model improved fit (AuROC=0.94). A baseline model including UC hospitalization in the past year and increased Bacteroidetes showed good fit characteristics for predicting increased risk of UC flare (AuROC=0.88). Conclusion Fecal microbial features at baseline and following therapy predict rCDI risk in patients with and without UC. These results may help risk stratify patients to guide management.