Ganoderma lucidum polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice

The morbidity of cardiovascular disease in postmenopausal patients increases due to the lack of estrogen protection. One of the most common conditions is hyperlipidemia characterized by abnormally elevated low‑density lipoprotein cholesterol (LDL‑C) and total cholesterol (TC). GLP has multiple effects such as lowering lipid levels, reducing inflammation, and regulating gut microbiota, but its effect on regulating metabolism in menopausal patients is not clear. The present study aimed to study the regulatory effect of Ganoderma lucidum polysaccharides (GLPs) on cholesterol metabolism in the liver. A bilateral ovariectomy mouse model was generated and GLP was given by gavage. Serum biochemistry, hepatic architecture and histopathology were assessed, expression of genes governing glucose and lipid homeostasis and circadian rhythm in the hepatic tissue was detected and the changes of intestinal microbiota of ovariectomized mice was analyzed by 16S rDNA sequencing. The GLPs directly affected the intestinal flora, upregulated the abundance of probiotics and improved the structure of microbiota and might indirectly affect the liver metabolism through the gut‑liver axis. GLP administration markedly lowered circulating TC and LDL‑C, decreased hepatic steatosis and modulated the expression of genes associated with the circadian clock, lipid synthesis and glucose metabolism in hepatic tissue. Collectively, these data position GLP as a promising therapeutic candidate for correcting postmenopausal dysmetabolism and curbing cardiovascular risk in aging female patients.