Flammulina velutipes Polysaccharides Demonstrate an Impact on Metabolic Regulation via Gender-specific Modification of Key Gut Microbiota in Mice

The objective of this study was to conduct a comprehensive evaluation of the transport characteristics, toxicological profiles, and functional physiological impacts of Flammulina velutipes polysaccharides (FVP), both in vitro and in vivo. Caco-2 cell model and murine model were employed to verify the objective in this paper, with a special emphasis on investigating gender-specific differences. The results revealed that FVP could traverse the Caco-2 cell monolayer via clathrin-dependent endocytosis. The acute oral toxicity assessment categorized FVP as minimally toxic. FVP administration led to a reduction in body weight, serum glucose and lipids levels on male and female mice, a mechanism attributed to the decreased gene expressions involved in glucose and lipids transporters in the intestinal tissue of mice. Moreover, FVP supplementation significantly influenced the levels of short-chain fatty acids and altered the abundance of pivotal gut microbiota, notably P. goldsteinii and P. johnsonii in male mice, and B. sartoii in female mice. PICRUSt analysis revealed enhanced functions in lipopolysaccharide biosynthesis, protein digestion and absorption in the intestine of male mice treated with FVP. Building upon our prior researches that underscored the multifaceted functional properties of FVP, this study further substantiates the functional characteristics of FVP in relation to glucose and lipid metabolism regulations.