Agaricus bisporus polysaccharides improve alcohol-associated liver disease by modulating the gut microbiota and metabolites

Alcohol-associated liver disease (ALD) is a common liver condition caused by excessive alcohol consumption. Currently, there is a lack of safe and effective targeted intervention strategies, posing a serious threat to human health. Due to their lack of toxic side effects and significant pharmacological effects, polysaccharides derived from edible and medicinal fungi show great potential for liver protection. In this research, a polysaccharide component with a molecular weight of 36.685 kDa was isolated and purified from the fruiting bodies of Agaricus bisporus . Structural analysis revealed that Abp-1 primarily consists of a backbone composed of →6)-α-D-Gal p -(1 → , →6)-α-D-Gal p -3-OMe-(1 → , →6)-β-D-Glc p -(1→ and →2,6)-α-D-Glc p -(1 → . Its side chains comprise α-L-Fuc p -(1 → , α-D-Man p -(1 → , and →2,6)-α-D-Glc p -(1 → . By establishing a mouse model of ALD, we analysed and evaluated the hepatoprotective function of Abp-1 and its regulatory mechanisms using biochemical assays, fecal transplantation and integrated multi-omics analysis. Animal studies have shown that Abp-1 diminishes oxidative damage and lipid lesions in the livers of ALD mice, regulates gut microbiota equilibrium in mice with hepatic injury, and preserves intestinal barrier integrity. Moreover, Abp-1 can enrich Lactobacillus reuteri , which produces the metabolite S-adenosylmethionine (SAMe) and modulates the FXR/AMPK/SREBP/ACC pathway to ameliorate ALD. This study has preliminarily identified an ALD intervention strategy with potential clinical applications, which may offer new insights into the treatment of ALD.