ABSTRACT
Objective To investigate the effects of cholesterol-lowering probiotics, DM9054 com-bined 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 liv-er and intestinal inflammatory genes and liver cholesterol synthesis genes. Western blot assay was used to de-tect 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. Con-clusions Cholesterol-lowering probiotics might attenuate NAFLD in mice through reducing liver cholesterol synthesis, alleviating liver and intestinal inflammation, improving intestinal mucosal barrier function and reg-ulating intestinal microbiota.