The protective mechanism ofLactobacillus plantarumFZU3013 against non-alcoholic fatty liver associated with hyperlipidemia in mice fed a high-fat diet

Lactobacillus plantarumFZU3013, a probiotic previously isolated from the traditional brewing process ofHongqurice wine, may have the beneficial effect of improving the disorders of lipid metabolism. This study aimed to investigate the role ofL. plantarumFZU3013 in improving non-alcoholic fatty liver (NAFL) associated with hyperlipidemia in mice fed a high-fat diet. The results indicated thatL. plantarumFZU3013 intervention significantly reduced the HFD-induced body weight gain and the abnormal levels of serum total triglycerides (TG), total cholesterol (TC) and low-density lipoprotein (LDL-C), and inhibited the excessive accumulation of liver lipids. In addition,L. plantarumFZU3013 also promoted the excretion of bile acids through feces. Metagenomic and multivariate statistical analysis revealed thatL. plantarumFZU3013 made significant structural changes in the intestinal microbiome of the mice fed with HFD, in particular by modulating the relative abundance of some function related microbial phylotypes. Furthermore, ultra-performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated thatL. plantarumFZU3013 had a significant regulatory effect on the composition of liver metabolites in hyperlipidemic mice, especially on the levels of some important biomarkers involved in the pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism,etc. Moreover,L. plantarumFZU3013 regulated the mRNA expression levels of the genes responsible for liver lipid and cholesterol metabolism.L. plantarumFZU3013 intervention increased the hepatic mRNA levels of cholesterol 7 alpha-hydroxylase (CYP7A1) and the bile salt export pump (BSEP), suggesting enhanced bile acid synthesis and excretion from the liver. These findings present new evidence supporting thatL. plantarumFZU3013 has the potential to improve lipid metabolism disorders through modulating specific intestinal microbial phylotypes and regulating hepatic lipid metabolism related genes, therefore it could be used as a potential functional food for the prevention of NAFL and hyperlipidemia.