This study’s objective was to examine the protective effect and mechanism of a novel polysaccharide (AYP) from Auricularia cornea var. Li. on alcoholic liver disease in mice. AYP was extracted from the fruiting bodies of Auricularia cornea var. Li. by enzymatic extraction and purified by DEAE-52 and Sephacryl S-400. Structural features were determined using high-performance liquid chromatography, ion exchange chromatography and Fourier-transform infrared analysis. Additionally, alcoholic liver disease (ALD) mice were established to explore the hepatoprotective activity of AYP (50, 100 and 200 mg/kg/d). Here, our results showed that AYP presented high purity with a molecular weight of 4.64 × 105 Da. AYP was composed of galacturonic acid, galactose, glucose, arabinose, mannose, xylose, rhamnose, ribos, glucuronic acid and fucose (molar ratio: 39.5:32.9:23.6:18.3:6.5:5.8:5.8:3.3:2:1.1). Notably, AYP remarkably reduced liver function impairment (alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC)), nitric oxide (NO) and malondialdehyde (MDA) of the liver and enhanced the activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione (gGSH)) in mice with ALD. Meanwhile, the serum level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were reduced in ALD mice treated by AYP. Furthermore, the AYPH group was the most effective and was therefore chosen to further investigate its effect on the intestinal microbiota (bacteria and fungi) of ALD mice. Based on 16s rRNA and ITS-1 sequencing data, AYP influenced the homeostasis of intestinal microbiota to mitigate the damage of ALD mice, possibly by raising the abundance of favorable microbiota (Muribaculaceae, Lachnospiraceae and Kazachstania) and diminishing the abundance of detrimental microbiota (Lactobacillus, Mortierella and Candida). This discovery opens new possibilities for investigating physiological activity in A. cornea var. Li. and provides theoretical references for natural liver-protecting medication research.
