Probiotics Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats via Gut Microbiota/FXR/FGF15 Signaling Pathway

Minmin Luo,Liyan Wu,Beihui He,Jianping Jiang,Junbin Yan,Jinting Wu,Zheng Chen,Zhiyun Chen,Fabiano Carvalho

doi:10.1155/2021/2264737

Abstract

Gut microbiota (GM) dysbiosis and bile acid (BA) metabolism disorder play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Probiotics had a beneficial effect on NAFLD, but further study is needed to explore probiotics as a potential therapeutic agent to NAFLD. The aim of this study was to investigate the regulatory effect of probiotics on gut microbiota in NAFLD rats and to explore the possible mechanism of probiotics regulating the bile acid receptor farnesoid X receptor/growth factor 15 (FXR/FGF15) signaling pathway in rats. We established a rat model of NAFLD fed with a high-fat diet (HFD) for 14 weeks, which was given different interventions (312 mg/kg/day probiotics or 10 mg/kg/day atorvastatin) from the 7th week. Serum lipids and total bile acids (TBA) were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE staining. The expression levels of FXR, FGF15 mRNA, and protein in rat liver were detected. 16S rDNA was used to detect the changes of gut microbiota in rats. Compared with the HFD group, probiotics and atorvastatin significantly reduced serum lipids and TBA levels. And probiotics increased dramatically the expression of FXR, FGF15 mRNA, and protein in the liver. But there were no significant changes in the atorvastatin group. Probiotics and atorvastatin can upregulate the diversity of gut microbiota and downregulate the abundance of pathogenic bacteria in NAFLD model rats. In summary, probiotics alleviated NAFLD in HFD rats via the gut microbiota/FXR/FGF15 signaling pathway.

Highlights

Nonalcoholic liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, which is predicted to become the most frequent indication for liver transplantation in the decade [1]
Many studies have revealed the role of gut microbiota in the pathophysiology of nonalcoholic fatty liver disease (NAFLD), including the dysbiosis of gut microbiota composition and abundance, which leads to the destruction of intestinal endothelial barrier function and can further induce bacterial translocation and liver inflammation [6, 7]
Hepatic inflammation was greatly improved after treatment with probiotics (HFD-P group) and atorvastatin (HFD-A group) (Figure 2)

Summary

Introduction

Nonalcoholic liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, which is predicted to become the most frequent indication for liver transplantation in the decade [1]. NAFLD is confined to liverrelated morbidity and mortality, but more and more evidence shows that NAFLD is a multifactorial disease It is strongly associated with dyslipidemia, obesity, hypertension, and diabetes [2, 3]. Bile acid metabolism plays an essential role in regulating the absorption of food lipids and cholesterol metabolism and participates in the balance of glucose and lipid metabolism, mainly by regulating farnesoid X receptor (FXR) and inducing the expression of fibroblast growth factor 15 (FGF15) [4, 5]. Many studies have revealed the role of gut microbiota in the pathophysiology of NAFLD, including the dysbiosis of gut microbiota composition and abundance, which leads to the destruction of intestinal endothelial barrier function and can further induce bacterial translocation and liver inflammation [6, 7].

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