Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis

Abstract: Bile reflux gastritis (BRG) is associated with the development of gastric cancer (GC), but the specific mechanism remains elusive. Here, a comprehensive study is conducted to explore the roles of refluxed bile acids (BAs) and microbiome in gastric carcinogenesis. The results show that conjugated BAs, interleukin 6 (IL‐6), lipopolysaccharide (LPS), and the relative abundance of LPS‐producing bacteria are increased significantly in the gastric juice of both BRG and GC patients. A secondary BA, taurodeoxycholic acid (TDCA), is significantly and positively correlated with the LPS‐producing bacteria in the gastric juice of these patients. TDCA promotes the proliferation of normal gastric epithelial cells (GES‐1) through activation of the IL‐6/JAK1/STAT3 pathway. These results are further verified in two mouse models, one by gavage of TDCA, LPS, and LPS‐producing bacteria (Prevotella melaninogenica), respectively, and the other by bile reflux (BR) surgery, mimicking clinical bile refluxing. Moreover, the bile reflux induced gastric precancerous lesions observed in the post BR surgery mice can be prevented by treatment with cryptotanshinone, a plant‐derived STAT3 inhibitor. These results reveal an important underlying mechanism by which bile reflux promotes gastric carcinogenesis and provide an alternative strategy for the prevention of GC associated with BRG.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis ; day:14 ; month:03 ; year:2022 ; extent:15
Advanced science ; (14.03.2022) (gesamt 15)

Urheber
Wang, Shouli
Kuang, Junliang
Zhang, Hongwei
Chen, Wenlian
Zheng, Xiaojiao
Wang, Jieyi
Huang, Fengjie
Ge, Kun
Li, Mengci
Zhao, Mingliang
Rajani, Cynthia
Zhu, Jinshui
Zhao, Aihua
Jia, Wei

DOI
10.1002/advs.202200263
URN
urn:nbn:de:101:1-2022032605344792886213
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:20 MESZ

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Beteiligte

  • Wang, Shouli
  • Kuang, Junliang
  • Zhang, Hongwei
  • Chen, Wenlian
  • Zheng, Xiaojiao
  • Wang, Jieyi
  • Huang, Fengjie
  • Ge, Kun
  • Li, Mengci
  • Zhao, Mingliang
  • Rajani, Cynthia
  • Zhu, Jinshui
  • Zhao, Aihua
  • Jia, Wei

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