Fig. 8: Schematic shows the underlying mechanisms of how gallstone-prone microbiota promotes cholesterol gallstone formation.
The gallstone-prone microbiota (enriched in Desulfovibrionales) modulated hepatic bile acid metabolism by (1) increased 7α-dehydroxylation bacteria to produce more secondary bile acids in the cecum, (2) produced H2S and regulated hepatic FXR-CYP7A expression, these (3) led to increasing DCA and decreasing βMCA, thereafter elevating hydrophobicity index of bile acids, inhibiting hepatic bile acid synthesis, (4) facilitating intestinal cholesterol absorption resulting in hepatic cholesterol overloading, and consequentially, (5) promoting canalicular cholesterol secretion into bile and inducing cholesterol gallstone formation.
