Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion. 2022

Hai Hu, and Wentao Shao, and Qian Liu, and Ning Liu, and Qihan Wang, and Jin Xu, and Xin Zhang, and Zhenkun Weng, and Qifan Lu, and Long Jiao, and Chaobo Chen, and Haidong Sun, and Zhaoyan Jiang, and Xiaoping Zhang, and Aihua Gu
Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of Medicine, Shanghai, China.

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, H2S 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.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002769 Cholelithiasis Presence or formation of GALLSTONES in the BILIARY TRACT, usually in the gallbladder (CHOLECYSTOLITHIASIS) or the common bile duct (CHOLEDOCHOLITHIASIS). Gallstone Disease,Cholelithiases,Gallstone Diseases
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D002790 Cholesterol 7-alpha-Hydroxylase A membrane-bound cytochrome P450 enzyme that catalyzes the 7-alpha-hydroxylation of CHOLESTEROL in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP7, converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of BILE ACIDS. CYP7,CYP7A,Cytochrome P-450 CYP7,CYP 7,CYP 7A,Cholesterol 7-alpha-Monooxygenase,Cholesterol 7alpha-Hydroxylase,Cholesterol-7-Hydroxylase,Cytochrome P450 7,Cholesterol 7 Hydroxylase,Cholesterol 7 alpha Hydroxylase,Cholesterol 7 alpha Monooxygenase,Cholesterol 7alpha Hydroxylase,Cytochrome P 450 CYP7
D004063 Digestion The process of breakdown of food for metabolism and use by the body.
D005243 Feces Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D000069196 Gastrointestinal Microbiome All of the microbial organisms that naturally exist within the GASTROINTESTINAL TRACT. Enteric Bacteria,Gastric Microbiome,Gastrointestinal Flora,Gastrointestinal Microbial Community,Gastrointestinal Microbiota,Gastrointestinal Microflora,Gut Flora,Gut Microbiome,Gut Microbiota,Gut Microflora,Intestinal Flora,Intestinal Microbiome,Intestinal Microbiota,Intestinal Microflora,Bacteria, Enteric,Flora, Gastrointestinal,Flora, Gut,Flora, Intestinal,Gastric Microbiomes,Gastrointestinal Microbial Communities,Gastrointestinal Microbiomes,Gastrointestinal Microbiotas,Gut Microbiomes,Gut Microbiotas,Intestinal Microbiomes,Intestinal Microbiotas,Microbial Community, Gastrointestinal,Microbiome, Gastric,Microbiome, Gastrointestinal,Microbiome, Gut,Microbiome, Intestinal,Microbiota, Gastrointestinal,Microbiota, Gut,Microbiota, Intestinal,Microflora, Gastrointestinal,Microflora, Gut,Microflora, Intestinal

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