Gut microbiota combined with serum metabolites to reveal the effect of Morchella esculenta polysaccharides on lipid metabolism disordered in high-fat diet mice

The ameliorating effects and mechanisms of Morchella esculenta polysaccharides (MEP-1) on lipid metabolism were investigated in high-fat diet (HFD) mice. The results showed that MEP-1 intervention significantly reduced serum TC, TG, LDL-C, and inflammatory factors (TNF-alpha, IL-1 beta and IL-6) in HFD mice in a dose-dependent manner, and high-dose (400 mg/kg/d) exhibited the most significant reductive effects. In addition, MEP-1 significantly recovered the gut microbiota disorders caused by HFD, especially decreasing the ratio of Firmicutes and Bacteroidetes (F/B) and increasing the dominant bacterial of Muribaculaceae_genus, Bacteroides, Alistipes and Enterococcus. Moreover, MEP-1 promoted the production of SCFAs and increased the expression levels of Occludin, Claudin and Muc2, also regulated lipid metabolism disorder and inflammation by inhibiting TLR4/ MyD88/NF-kappa B via the gut-liver axis. In addition, serum metabolomic analysis revealed that l-phenylalanine, larginine and acetylcholine were significantly upregulated with MEP-1 intervention, and were negatively correlated with blood lipid level, in which l-arginine could activate NO/PPAR alpha/CPT1A pathway to ameliorate lipid metabolism disorders. Such results demonstrated that gut microbiota, amino acid metabolic and insulin secretion pathways might be the important factors that mediated the regulation of MEP-1 in lipid metabolism. The results also provided new evidence and strategies for the application of MEP-1 as functional foods.