Recent reports suggest that gut microbiota can be a major determinant of dyslipidemia and non-alcoholic fatty liver disease (NAFLD) and its modulation by treating probiotics is a valid strategy to exert a protective effect. In this study, high-fat diet (HFD)-fed mice were orally administrated with Lactobacillus rhamnosus GG (LGG) for 13 weeks. Significant reductions in the weights of the liver, mesenteric and subcutaneous adipose tissues were observed in LGG-treated HFD-fed mice compared to LGG-non-treated controls. The serum levels of triglyceride and cholesterol were also significantly reduced in LGG-treated mice. Gut microbial composition analysis showed that shifts in the diversity of dominant gut bacteria were caused by HFD and restored by LGG treatment. A remarkable decrease of hepatic fat content was also observed in LGG-treated mice, accompanied by downregulated expressions of lipogenic and pro inflammatory genes in the liver. LGG-treated mice had lower expression levels of genes involved in cholesterol synthesis, but conversely, higher expression levels of cholesterol efflux-related genes compared to LGG-non-treated controls. The cholesterol-lowering effect of LGG was also found to be mediated by suppression of FXR and FGF15 signaling, resulting in the upregulation of hepatic CYP7A1. Our findings confirm a therapeutic potential of probiotics for ameliorating dyslipidemia and NAFLD. (C) 2016 Elsevier Inc. All rights reserved.