Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number2200263
Number of pages15
JournalAdvanced Science
Volume9
Issue number16
Early online date14 Mar 2022
DOIs
Publication statusPublished - 3 Jun 2022

Scopus Subject Areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

User-Defined Keywords

  • bile acid
  • bile reflux
  • gastric carcinogenesis
  • microbiome

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