2. Academic Validation
  3. Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy

Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy

  • Nat Commun. 2023 Mar 9;14(1):1305. doi: 10.1038/s41467-023-36981-4.
Bo Tang # 1,  Li Tang # 1,  Shengpeng Li 1,  Shuang Liu 1,  Jialin He 1,  Pan Li 2,  Sumin Wang 1,  Min Yang 1,  Longhui Zhang 3,  Yuanyuan Lei 1,  Dianji Tu 4,  Xuefeng Tang 5,  Hua Hu 3,  Qin Ouyang 6,  Xia Chen 7,  Shiming Yang 8 9 10
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 2 Department of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan, Guangdong, China.
  • 3 Department of Obstetrics and Gynecology, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 4 Laboratory Medicine Center, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 5 Department of Pathology, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 6 College of Pharmacy, Army Medical University, Chongqing, China.
  • 7 Department of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan, Guangdong, China. 2676832333@qq.com.
  • 8 Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China. Yangshiming@tmmu.edu.cn.
  • 9 Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, China. Yangshiming@tmmu.edu.cn.
  • 10 Chongqing Municipality Clinical Research Center for Gastroenterology, Chongqing, China. Yangshiming@tmmu.edu.cn.
  • # Contributed equally.
PMID: 36894566 DOI: 10.1038/s41467-023-36981-4
Abstract

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.

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