Fecal Microbiota Transplantation from Noni Fruit Phenolic-Rich Extract Intervention Mouse Donors Ameliorates Lipid Metabolism Disorder by Regulating the FXR–FGF15 Pathway in a Gut Microbiota-Dependent Manner

Noni fruit phenolic-rich extract (NFE) has been confirmed to alleviate lipid metabolism disturbance, with emerging evidence implicating bile acids (BAs) metabolism in a gut microbiota-dependent manner in mediating the effect. The effect and potential mechanism of fecal microbiota transplantation from NFE intervention mouse donors (FMT-NFE) on lipid metabolism disorder were investigated. The results reveal FMT-NFE intervention regulated the body weight, lipid profile levels, and liver damage. FMT-NFE intervention upgraded the abundance of bile salt hydrolase (BSH)-expressing bacteria and short-chain fatty acid (SCFA)-producing bacteria in feces, which is accompanied by changes of BSH activity and BAs profile as well as elevation of the SCFA level. Moreover, western blotting and immunofluorescence results confirmed the intestinal FXR-FGF15 pathway was activated by FMT-NFE intervention, which was accompanied by activation of the liver FXR and inhibition of CYP7A1 expression to control cholesterol-to-BAs conversion. These findings underscore the mechanisms behind maintaining BAs and lipid metabolism homeostasis of NFE.