The dose-dependent mechanism behind the protective effect of lentinan against acute alcoholic liver injury via proliferating intestinal probiotics

Abstract

Acute alcoholic liver injury (AALI) is a widespread disease that can develop into hepatitis, liver fibrosis, and cirrhosis. In severe cases, it can be life-threatening, while drug treatment presents various side effects. This study characterized the structure of natural lentinan (LNT) from the Qinba Mountain area and investigated the protective mechanism of different LNT doses (100 mg kg⁻¹, 200 mg kg⁻¹, and 400 mg kg⁻¹) on AALI. The results showed that LNT was a glucose-dominated pyran polysaccharide with a triple-helical structure and a molecular weight (M_w) of 7.56 × 10⁶ Da. An AALI mouse model showed that all the LNT doses protected liver function, reduced hepatic steatosis, alleviated oxidative stress and inflammatory response, and stimulated probiotic proliferation. Low-dose LNT increased anti-oxidant-associated beneficial bacteria, medium-dose LNT improved liver swelling and promoted anti-oxidant-associated probiotics, and high-dose LNT increased the probiotics that helped protect liver function and anti-oxidant and anti-inflammatory properties. All the LNT doses inhibited pathogenic growth, including Oscillospiraceae, Weeksellaceae, Streptococcaceae, Akkermansiaceae, Morganellaceae, and Proteus. These results indicated that the protective effect of LNT against AALI was mediated by the proliferation of various intestinal probiotics and was related to the consumption doses. These findings offer new strategies for comprehensively utilizing Lentinula edodes from the Qinba Mountain area and preventing AALI using natural food-based substances.