A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome

作者：Ling Zhao, Wei Yang, Yang Chen, Fengjie Huang, Lin Lü, Chengyuan Lin, Tao Huang, Ziwan Ning, Lixiang Zhai, Linda L. D. Zhong, Wai-Ching Lam, Zhen Yang, Xuan Zhang, Chung Wah Cheng, Lijuan Han, Qinwei Qiu, Xiaoxiao Shang, Runyue Huang, Haitao Xiao, Zhenxing Ren, Dongfeng Chen, Silong Sun, Hani S El-Nezami, Zongwei Cai, Aiping Lü, Xiaodong Fang, Wei Ping Jia, Zhaoxiang Bian · 发表于：Journal of Clinical Investigation · 年份：2019 · DOI：10.1172/jci130976 · 被引用次数：204 · 研究领域：Gastrointestinal motility and disorders、Gut microbiota and health、Pancreatitis Pathology and Treatment

An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.