TY - JOUR
T1 - Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis
AU - Wang, Shouli
AU - Kuang, Junliang
AU - Zhang, Hongwei
AU - Chen, Wenlian
AU - Zheng, Xiaojiao
AU - Wang, Jieyi
AU - Huang, Fengjie
AU - Ge, Kun
AU - Li, Mengci
AU - Zhao, Mingliang
AU - Rajani, Cynthia
AU - Zhu, Jinshui
AU - Zhao, Aihua
AU - Jia, Wei
N1 - Funding Information:
This work was funded by the National Natural Science Foundation of China (81772530, 81974073, 82170833, 82122012) and Natural Science Foundation of Shanghai (21ZR1448800). The authors also thank Wenming Zhang for helping to collect the gastric juice samples. The authors also thank director of Wenqi Tao (Shanghai Jiao Tong University Affiliated Sixth People's Hospital) for helping pathological section analysis.
Publisher Copyright:
© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH
PY - 2022/6/3
Y1 - 2022/6/3
N2 - 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.
AB - 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.
KW - bile acid
KW - bile reflux
KW - gastric carcinogenesis
KW - microbiome
UR - http://www.scopus.com/inward/record.url?scp=85126250155&partnerID=8YFLogxK
U2 - 10.1002/advs.202200263
DO - 10.1002/advs.202200263
M3 - Journal article
C2 - 35285172
AN - SCOPUS:85126250155
SN - 2198-3844
VL - 9
JO - Advanced Science
JF - Advanced Science
IS - 16
M1 - 2200263
ER -
