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 conju...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202200263 |
| _version_ | 1818233112579014656 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shouli Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T11:17:00Z |
| format | Article |
| id | doaj.art-6ba9675330134329aedc54bfb0538bb9 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-12T11:17:00Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-6ba9675330134329aedc54bfb0538bb92022-12-22T00:26:08ZengWileyAdvanced Science2198-38442022-05-01916n/an/a10.1002/advs.202200263Bile Acid–Microbiome Interaction Promotes Gastric CarcinogenesisShouli Wang0Junliang Kuang1Hongwei Zhang2Wenlian Chen3Xiaojiao Zheng4Jieyi Wang5Fengjie Huang6Kun Ge7Mengci Li8Mingliang Zhao9Cynthia Rajani10Jinshui Zhu11Aihua Zhao12Wei Jia13Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaDepartment of Metabolic and Bariatric Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCancer Institute, Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCancer Biology Program University of Hawaii Cancer Center Honolulu HI 96813 USADepartment of Gastroenterology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaCenter for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaAbstract 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.https://doi.org/10.1002/advs.202200263bile acidbile refluxgastric carcinogenesismicrobiome |
| spellingShingle | 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 Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis Advanced Science bile acid bile reflux gastric carcinogenesis microbiome |
| title | Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis |
| title_full | Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis |
| title_fullStr | Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis |
| title_full_unstemmed | Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis |
| title_short | Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis |
| title_sort | bile acid microbiome interaction promotes gastric carcinogenesis |
| topic | bile acid bile reflux gastric carcinogenesis microbiome |
| url | https://doi.org/10.1002/advs.202200263 |
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