Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China.
Department of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan, Guangdong, China.
Nat Commun. 2023 Mar 9;14(1):1305. doi: 10.1038/s41467-023-36981-4.
Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment.
妊娠肝内胆汁淤积症（ICP）是一种女性特有的妊娠疾病，其特征是血清胆汁酸升高和不良胎儿结局。ICP 的病因和发病机制尚不清楚；因此，现有的治疗方法在很大程度上是经验性的。在这里，我们发现 ICP 患者和健康孕妇的肠道微生物组有显著差异，并且 ICP 患者的肠道微生物组定植足以在小鼠中诱导胆汁淤积。ICP 患者的肠道微生物组主要以脆弱拟杆菌（Bacteroides fragilis，B. fragilis）为特征，B. fragilis 能够通过其 BSH 活性抑制 FXR 信号转导来调节胆汁酸代谢，从而促进 ICP 的发生。B. fragilis 介导的 FXR 信号转导抑制负责过量的胆汁酸合成，并中断肝内胆汁排泄，最终促进 ICP 的发生。我们提出，调节肠道微生物群-胆汁酸-FXR 轴可能对 ICP 的治疗有价值。
