Butyrate-producing commensal bacteria mediates the efficacy of herbal medicine JCM-16021 on abdominal pain in diarrhea-predominant irritable bowel syndrome: a randomized clinical trial

BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) presents significant treatment challenges due to limited therapeutic options that effectively target the underlying pathophysiological mechanisms. In this study, we performed a multi-center, double-blind randomized placebo-controlled trial to investigate the efficacy and safety of herbal medicine JCM-16021 on IBS-D with a focus on its effects on gut microbiota. RESULTS: Our study assessed the clinical efficacy and safety of JCM-16021 in alleviating abdominal pain in IBS-D patients. The results suggested that JCM-16021 is both effective and safe, with its therapeutic effects closely linked to the modulation of short-chain fatty acid (SCFA) producers. Through fecal microbiota transplantation (FMT) experiments in mice, we showed that SCFA producers mediate the alleviation of abdominal pain symptoms by the JCM-16021 treatment. In a TNBS-induced mouse model of IBS, we showed that butyrate producers enriched by JCM-16021 significantly ameliorate abdominal pain. Importantly, baseline gut microbial profiles, such as the presence of Eubacterium rectale in IBS-D patients are predictive of their responses to JCM-16021 treatment. CONCLUSIONS: Our findings not only affirm the efficacy of JCM-16021 in mitigating abdominal pain in IBS-D patients but also highlight a microbiota-dependent mechanism, underscoring the therapeutic potential of gut microbiota modulation in treating gastrointestinal disorders. By combining clinical trials in humans with biological experiments in mice, this study establishes a translational approach to investigate the role of gut microbiota in the treatment of herbal medicine. CLINICALTRIALS: gov no: NCT03457324.