Therapeutic Mechanisms of Lactiplantibacillus plantarum NXU0014 Against Chronic Alcohol-Induced Liver Injury Mediated by Gut-Liver Axis Modulation.

Abstract

This study investigated the protective effects of Lactobacillus plantarum NXU0014 against chronic alcoholic liver injury (CALI) and its underlying mechanisms in a mouse model. Forty-eight male C57BL/6J mice were divided into four groups: blank control, model, silymarin, and L. plantarum NXU0014. The CALI model was induced by administering 56% Hongxing Erguotou liquor. Multi-omics analyses revealed that alcohol intake induced gut microbiota dysbiosis, characterized by an increased Firmicutes/Bacteroidetes ratio and decreased abundance of probiotics (e.g., Lactobacillus and Bifidobacterium). These changes were associated with hepatic pro-inflammatory upregulation, downregulation of antioxidant genes (Nrf2, HO-1), and impaired intestinal barrier function (ZO-1). Metabolomic disturbances featured elevated fecal bile acids, reduced amino acids, and enriched pathways for ABC transporters and bile secretion. Intervention with NXU0014 restored probiotic levels (including Bifidobacterium pseudodanubicum and Lactobacillus reuteri), alleviated hepatic inflammation and oxidative stress by activating the Nrf2/HO-1 pathway, and repaired the intestinal barrier. Integrated microbiome-metabolome analysis revealed a negative correlation between Lactobacillus and toxic bile acids, and a positive correlation between Bifidobacterium and anti-inflammatory metabolites. These findings demonstrate that NXU0014 mitigates liver injury by modulating gut-liver axis metabolic interactions, highlighting its potential as a novel probiotic-based therapy for alcoholic liver disease.