Flammulina velutipes polysaccharide counteracts cadmium-induced gut injury in mice via modulating gut inflammation, gut microbiota and intestinal barrier

Cadmium (Cd), as Group I carcinogen, can induce damage to various organs including the gut. It is of great importance to meet the rising demand for effective therapies against Cd-induced damage and investigate the mechanism. Flammulina velutipes is a popular edible mushroom, despite the well-known health benefits of Flammulina velutipes , little is known about the effect of its polysaccharide (FVP) against CdCl 2 -intestinal injury. In this study, a FVP (uronic acid, 5.10 %; degree of methylation, 41.24 %) was produced via hot water extraction (85 °C) and ethanol precipitation. The FVP contained eight major monosaccharides and exhibited good thermal stability at temperatures lower than 139.73 °C. FVP (100 mg/kg b. w., gavage for 4 weeks) alleviated CdCl 2 (1.5 mg/kg b. w., gavage for 4 weeks)-induced intestinal inflammation and apoptosis, intestinal permeability alteration and intestinal barrier disruption. FVP increased the abundance of Bacteroides , whilst decreasing the abundance of Desulfovibrionales and Clostridium . FVP also restored the levels of short-chain fatty acids (SCFAs), including acetic, propionic, isobutyric, butyric, isovaleric and valeric acids. Correlation analysis indicated the interplays among the FVP, gut microbes, SCFAs, intestinal barrier/cells and gut inflammation. FVP enhances the metabolic functions of gut microbiota via functional pathways analyzed by KEGG database. Furthermore, gut microbial transplantation of FVP + CdCl 2 group mice partially alleviated CdCl 2 caused-gut damage. Thus, FVP may be an effective therapeutic agent against CdCl 2 -induced gut damage via SCFA-mediated regulation of intestinal inflammation and gut microbiota-related energy metabolism. This study may open a new avenue for developing alternative strategies to prevent CdCl 2 -caused injury.