Effects of cholesterol-lowering probiotics on intestinal barrier and gut microbiota in mice with non-alcoholic fatty liver disease and the possible mechanisms

Abstract

Objective To investigate the effects of cholesterol-lowering probiotics, DM9054 combined with 86066, on the intestinal mucosal barrier and gut microbiota in mice with nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet and the possible mechanisms. Methods Twenty-four male mice deficient in the low-density lipoprotein receptor gene (Ldlr- / - mice) were randomly divided into three groups including control, NAFLD model and probiotic intervention groups. Mice in the three groups were given normal chow diet+ normal saline, high-fat diet (HFD)+ normal saline, and HFD+ cholesterol-lowering probiotics, respectively. The mouse model of NAFLD was established by feeding mice with high-fat diet (45% of calories derived from fat diet) for 12 weeks. qPCR was performed to measure the expression of liver and intestinal inflammatory genes and liver cholesterol synthesis genes. Western blot assay was used to detect the expression of intestinal tight junction proteins and HMG-CoA reductase (HMGCR). Pathological changes in tissues were evaluated by HE staining. Features of gut microbiota were analyzed by 16S rRNA gene sequencing. Results Cholesterol-lowering probiotics intervention attenuated HFD-induced hepatic steatosis, inflammatory responses and obesity and decreased the synthesis of liver cholesterol (P<0.05). Moreover, inhibited gut inflammatory responses and improved intestinal barrier function were detected in the probiotic intervention group (P<0.05). The composition of gut microbiota in mice of the probiotic intervention group was different from that of the model group, but similar to that of the control group. Conclusions Cholesterol-lowering probiotics might attenuate NAFLD in mice through reducing liver cholesterol synthesis, alleviating liver and intestinal inflammation, improving intestinal mucosal barrier function and regulating intestinal microbiota. Key words: Nonalcoholic fatty liver disease (NAFLD); Probiotics; Intestinal barrier function; Intestinal microbiota