Microbiome and Metabolome Restoration After Administration of Fecal Microbiota, Live-jslm (REBYOTA®) for Preventing Recurrent Clostridioides difficile Infection

Abstract Background Microbiota-based treatments are effective in preventing recurrent Clostridioides difficile infection. Fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660) was shown to prevent recurrent C difficile infection in a phase 3 clinical trial (PUNCH CD3) based on a randomized, double-blinded, placebo-controlled design. Methods Stool samples from participants in PUNCH CD3 who received a single blinded dose of rectally administered RBL or placebo were sequenced to determine microbial community composition and calculate the Microbiome Health Index for postantibiotic dysbiosis. The composition of bile acids (BAs) in the same samples was quantified by liquid chromatography–mass spectrometry. Relationships between BA composition and microbiota community structure and correlations with treatment outcomes were assessed. Results Before administration, Gammaproteobacteria and Bacilli dominated the microbiota community, and primary BAs were more prevalent than secondary BAs. Clinical success after administration correlated with shifts to predominantly Bacteroidia and Clostridia, a significant increase in Microbiome Health Index for postantibiotic dysbiosis, and a shift from primary to secondary BAs. Several microbiota and BA changes were more extensive in RBL-treated responders as compared with placebo-treated responders, and microbiota changes correlated with BA changes. Conclusions Clinical response and RBL administration were associated with significant restoration of microbiota and BA composition. Clinical Trials Registration NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).