Chronic alcohol consumption compromises gut barrier integrity and promotes endotoxemia: Implications for sepsis susceptibility in immunocompromised hosts

BACKGROUND: Gut barrier integrity prevents microbial translocation and systemic infection. Chronic alcohol disrupts this barrier, but its role in infection susceptibility among immune-compromised hosts remains unclear. We investigated how chronic alcohol promotes gut barrier dysfunction, endotoxemia, and dysbiosis, predisposing to bacterial translocation and sepsis. METHODS: and wild-type mice received oral gavage of 35% ethanol (4.2 g/kg/day) or water for 10 weeks. Gut barrier integrity was assessed by serum endotoxin, FITC-dextran permeability, ileal claudin-1, and intestinal IgG/neutrophil infiltration. Systemic inflammation was evaluated by serum TNF-α, IL-1β, and IL-6; gut microbiota by 16S rRNA sequencing. Bone marrow-derived macrophages and hepatocytes from both genotypes were stimulated with LPS or ethanol to assess inflammatory responses, mitochondrial damage, and cGAS-STING activation. RESULTS: cells producing greater cytokine levels. Both stimuli caused comparable mitochondrial damage and cGAS-STING activation. CONCLUSIONS: Alcohol-induced gut barrier dysfunction, endotoxemia, and dysbiosis predispose to bacterial translocation and early sepsis, particularly in hosts with impaired inhibitory Fcγ receptor signaling, supporting gut barrier preservation as a strategy for preventing alcohol-associated infections and sepsis.