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
Lixiang Zhai, Ya Zheng, Cho Wing Lo, Shujun Xu, Xuanting Jiang, Qin Liu, Jessica Ching, Ziwan Ning, Gengyu Bao, Wei Yang, Qiuqin Zhang, Chung Wah Cheng, Wai Ching Lam, Kam Leung Chan, Xuan Zhang, Pui Yan Lam, Xing Wu, Linda L. D. Zhong, Pei Hua Cao, Matthew Koh, Pui Kuan Cheong, Zhixiu Lin, Chengyuan Lin, Ling Zhao, Xavier Hoi Leong Wong, Justin CY Wu, Zhaoxiang Bian
Abstract
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.