Xiaohua Funing decoction ameliorates non-alcoholic fatty liver disease by modulating the gut microbiota and bile acids.

INTRODUCTION

The gut microbiota and bile acids (BAs) have emerged as factors involved in the development of non-alcoholic fatty liver disease (NAFLD). Xiaohua Funing decoction (XFD) is a traditional Chinese medicine formula used for the treatment of NAFLD. Previous studies have indicated that XFD protects liver function, but the underlying mechanism remains unclear.

METHODS

In this study, a Wistar rat model of NAFLD (Mod) was established via a high-fat diet. The effects of obeticholic acid (OCA) and XFD on Mod rats were subsequently evaluated. Wistar rats in the control (Con) group were fed a standard diet. There were eight rats in each group, and the treatment lasted for 12 weeks. Furthermore, metagenomic sequencing and BA metabolomic analyses were performed.

RESULTS

Compared to the Con group, the Mod group presented significant differences in body and liver weights; serum total cholesterol (TC) and triglyceride (TG) levels; and liver TG, TC, and bile salt hydrolase levels (p < 0.05 or p < 0.01). Importantly, OCA and XFD administration normalized these indicators (p < 0.05 or p < 0.01). Pathology of the liver and white fat steatosis was observed in the Mod group, but steatosis was significantly alleviated in the OCA and XFD groups (p < 0.05 or p < 0.01). The abundances of Bacteroidales_bacterium, Prevotella_sp., bacterium_0.1xD8-71, and unclassified_g_Turicibacter in the Mod group were significantly different from those in the Con group (p < 0.05 or p < 0.01), whereas the abundance of Bacteroidales_bacterium was greater in the XFD group. A total of 17, 24, and 24 differentially abundant BAs were detected in the feces, liver, and serum samples from the Mod and Con groups, respectively (p < 0.05 or p < 0.01). In the feces, liver, and serum, XFD normalized the levels of 16, 23, and 14 BAs, respectively, including glycochenodeoxycholic acid, deoxycholic acid, murideoxycholic acid, lithocholic acid, 23-nordeoxycholic acid, and 3β-ursodeoxycholic acid. In addition, glycochenodeoxycholic acid was identified as a potential biomarker of NAFLD.

DISCUSSION: In summary, our experiments revealed that XFD regulates the gut microbiota and BAs, providing beneficial effects on liver lipid accumulation in NAFLD.