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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\u20106), lipopolysaccharide (LPS), and the relative abundance of LPS\u2010producing 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\u2010producing bacteria in the gastric juice of these patients. TDCA promotes the proliferation of normal gastric epithelial cells (GES\u20101) through activation of the IL\u20106\/JAK1\/STAT3 pathway. These results are further verified in two mouse models, one by gavage of TDCA, LPS, and LPS\u2010producing bacteria (\n                    <jats:italic>Prevotella melaninogenica<\/jats:italic>\n                    ), 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\u2010derived 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.\n                  <\/jats:p>","DOI":"10.1002\/advs.202200263","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T03:54:24Z","timestamp":1647230064000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Bile Acid\u2013Microbiome Interaction Promotes Gastric Carcinogenesis"],"prefix":"10.1002","volume":"9","author":[{"given":"Shouli","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai 200233 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