The gut-brain axis as a therapeutic target in alcohol use disorder: dietary fiber, intestinal barrier integrity, and neuroinflammatory mechanisms underlying depression

Abstract

Alcohol use disorder is frequently accompanied by major depressive disorder, yet the biological mechanisms linking both conditions remain incompletely understood. Increasing evidence suggests that chronic alcohol consumption disrupts the gut-brain axis by damaging intestinal tight junctions and inducing gut dysbiosis characterized by depletion of short-chain fatty acid-producing bacteria. The resulting impairment of intestinal barrier integrity may facilitate the translocation of bacterial lipopolysaccharide, promoting peripheral and central neuroinflammation through Toll-like receptor 4-dependent pathways. These neuroinflammatory alterations may persist during abstinence and contribute to glutamatergic, dopaminergic, and serotonergic dysregulation associated with depressive symptoms and relapse vulnerability. This Perspective proposes that intestinal barrier dysfunction represents an actionable upstream mechanism linking alcohol-induced gut dysbiosis with neuroinflammation, depression, and relapse vulnerability, and highlights dietary fiber supplementation as a physiologically grounded, accessible nutritional strategy to enhance endogenous butyrate production, improve intestinal barrier integrity, and attenuate neuroinflammatory signaling. Available preclinical and clinical evidence is critically evaluated, and key priorities for future mechanistic and clinical studies are outlined.