Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion.
Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion.
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肠道微生物群通过调节胆汁酸组成和胆汁胆固醇分泌来促进胆固醇胆结石的形成。
DOI：
10.1038/s41467-021-27758-8
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发表时间：
2022-01-11
影响因子：
16.6
通讯作者：
Gu A
中科院分区：
文献类型：
--
作者：
Hu H;Shao W;Liu Q;Liu N;Wang Q;Xu J;Zhang X;Weng Z;Lu Q;Jiao L;Chen C;Sun H;Jiang Z;Zhang X;Gu A
胆固醇结石病是一种世界性的常见病。胆囊胆汁中胆固醇过饱和是其发病的前提条件，但其发病机制尚未完全阐明。在这项研究中，我们发现胆结石患者肠道菌群（尤其是脱硫弧菌）富集。将来自胆结石患者的肠道菌群粪便移植到胆结石抗性品系小鼠可以诱导胆结石形成。携带脱硫弧菌与增加盲肠次级胆汁酸产生和增加胆汁酸疏水性相关，促进肠道胆固醇吸收。同时，脱硫弧菌目的代谢产物H2S增加，并显示诱导肝脏FXR和抑制CYP 7A 1表达。小鼠携带脱硫弧菌可诱导肝脏胆固醇转运蛋白Abcg 5/g8的表达，促进胆汁胆固醇的分泌。我们的研究证明了肠道微生物群脱硫弧菌目作为环境调节剂的作用，通过其对胆汁酸和胆固醇代谢的影响促进胆结石形成。
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 (especiallyDesulfovibrionales)in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. CarryingDesulfovibrionalesis associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product ofDesulfovibrionales, H2S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carryingDesulfovibrionalespresent induction of hepatic expression of cholesterol transportersAbcg5/g8to 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.
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