Rifaximin is associated with modest, transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome

Objective: Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between intestinal microbiota and IBS, this study examined potential effects of rifaximin on the gastrointestinal microbial community in patients with IBS-D. Design: TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label rifaximin 550 mg three times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive two repeat courses of rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. At the beginning and end of each course of treatment, stool samples were collected from a random subset of patients, and, as a secondary analysis to TARGET 3, the composition and diversity of the gut microbiota were assessed using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Results: Samples from 103 patients were included. After open-label rifaximin treatment for 2 weeks, 11 taxa (eg, Clostridiaceae, Enterobacteriaceae, Bifidobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of rifaximin were generally short-term, as there were few significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The state of the microbial community at baseline had modest but statistically significant power to predict which patients responded to rifaximin treatment (p=0.001). Conclusion: The results suggest that rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by rifaximin are causally linked to IBS-D.