Chronic alcohol consumption-induced alterations in gut microbiota disrupt the integrity of the intestinal barrier

Chronic alcohol consumption is known to compromise the intestinal barrier and disrupt gut homeostasis, contributing to increased vulnerability to various diseases; however, the precise mechanisms remain poorly understood. Emerging evidence suggests that alcohol-induced alterations in host metabolism and gut microbiota composition play a critical role in driving intestinal barrier dysfunction. In this study, we employed a mouse model of chronic alcohol gavage to investigate these interactions. Untargeted metabolomics analysis revealed significant perturbations in isoflavone metabolism caused by chronic alcohol exposure. These metabolic disturbances were accompanied by notable shifts in gut microbiota composition, including an enrichment of Colidextribacter and Ruminococcus. Transcriptomic analysis further identified 286 upregulated and 367 downregulated genes in the alcohol group, and demonstrated that these microbial changes were strongly associated with the downregulation of the Ccr2 gene in intestinal cells, implicating this pathway in intestinal barrier dysfunction. Taken together, these findings suggest that alcohol-induced disruptions in isoflavone metabolism contribute to gut microbiota imbalances, which were associated with suppressed Ccr2 expression and impaired intestinal barrier integrity, although causal relationships and the specific cell types involved remain to be determined, providing new insights into the mechanisms underlying alcohol-related gut pathology.