Abstract: This study shed light on the hepatoprotective mechanism of β-glucan from Ganoderma sinense produced in Wuping, China on mice with acute alcoholic liver injury (AALI) through studies on the correlation between the gut microbiota and its metabolites. A total of 180 specific pathogen-free (SPF)-grade mice were randomly assigned to six groups: two control groups (CK and A, gavaged with distilled water and carboxymethyl cellulose sodium (CMC-Na), respectively), two model groups (C and D, gavaged with distilled water and CMC-Na, respectively), an experimental group (D, gavaged with 200 mg/kg of G. lucidum β-glucan), and a positive control group (E, gavaged with 300 mg/kg of diphenyl diester). After one week of continuous administration, serum and liver biochemical indices were measured in each group and histopathological observation of liver sections was studied. Meanwhile, the differences in the composition of the intestinal microbiota and metabolites were analyzed among groups. The results indicated that oral administration of 200 mg/kg of G. sinense β-glucan ameliorated liver function in AALI mice. Compared with the model groups, the experimental group exhibited significantly reduced levels of alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA) and alcohol dehydrogenase (ADH) (P < 0.05) and significantly increased levels of total superoxide dismutase (T-SOD) and reduced glutathione (GSH) (P < 0.05). Histopathological observation confirmed that β-glucan from G. lucidum significantly attenuated liver cell and lobular lesions, thereby exerting a hepatoprotective effect. G. sinense β-glucan improved the gut microbiota and substance metabolism in mice. Specifically, compared with the model group, the ratio of Firmicutes/Bacteroidoota (F/B) increased in the experimental group, and the relative abundance of beneficial bacteria such as GCA-900066575 and Roseburia in Firmicutes significantly increased as well. Additionally, G. sinense β-glucan altered the metabolism of lipids and lipid-like molecules such as cholesterol, DHA ethyl ester, and oleic acid methyl ester through affecting Bacteroides in the Bacteroidota phylum and altered propionic acid metabolism through affecting Lactobacillus in the Firmicutes phylum, thereby alleviating AALI. Therefore, the protective mechanism of G. sinense polysaccharides against AALI in mice might be related to the regulation of amino acid metabolism, lipid and lipid-like molecule metabolism, and propionic acid metabolism by improving the composition of the gut microbiota.

Key words: Ganoderma sinense from Wuping, β-glucan, acute alcoholic liver injury, gut microbiota, intestinal metabolites, hepatoprotective effect