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Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion
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Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion
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Journal Article
Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion
2022
Overview
Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially
Desulfovibrionales)
in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying
Desulfovibrionales
is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of
Desulfovibrionales
, H
2
S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying
Desulfovibrionales
present induction of hepatic expression of cholesterol transporters
Abcg5/g8
to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota,
Desulfovibrionales
, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.
Metabolic conditions associated with alterations of the gut microbiome, such as obesity and diabetes, predispose to gallstone disease. Here the authors demonstrate that the gut microbiome, in particular the genus Desulfovibrionale, contribute to gallstone formation in mice.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/90
/ 692/4020/1503/1328/1498/1376
/ 82/1
/ 82/80
/ Animals
/ Bile
/ Bile Acids and Salts - metabolism
/ Calculi
/ Cecum
/ Cholesterol 7-alpha-Hydroxylase - genetics
/ Cholesterol 7-alpha-Hydroxylase - metabolism
/ Desulfovibrionales - physiology
/ Gastrointestinal Microbiome - physiology
/ Humanities and Social Sciences
/ Liver
/ Male
/ Mice
/ Science
