Gut microbiota associated with clinical relapse in patients with quiescent ulcerative colitis

Background: The microbiota associated with relapse in patients with quiescent ulcerative colitis (qUC) remains unclear. Our objective was to analyze the fecal microbiota of Japanese patients with qUC and identify the relapse-associated microbiota. Methods: Fifty-nine patients with qUC and 59 healthy controls (HCs) were enrolled in the study (UMIN 000019486), and their fecal microbiota was compared using 16S rRNA gene amplicon sequencing. We followed their clinical course up to 3.5 years and analyzed the relapse-associated microbiota. Potential functional changes in the fecal microbiota were evaluated using PICRUSt software and Kyoto Encyclopedia of Genes and Genomes database. Results: There were significant differences in the diversity of fecal microbiota between HC and qUC subjects, with differences observed in the abundance of 46 genera. Despite no significant difference in variation of microbiota in a single sample (alpha diversity) between patients in sustained remission and relapsed patients, the variation in microbial communities between samples (beta diversity) was significantly different. Prevotella was more abundant in the sustained remission patients, whereas Faecalibacterium and Bifidobacterium were more abundant in the relapsed patients. We clustered the entire cohort into four clusters, and Kaplan-Meier analysis revealed the subsequent clinical course of each cluster was different. We identified 48 metabolic pathways associated with each cluster using linear discriminant analysis effect size. Conclusions: We confirmed the difference in microbiota between patients with qUC and HCs and identified three genera associated with relapse. We found that the clusters based on these genera had different subsequent clinical courses and activated different metabolic pathways.