Dietary fiber as a therapeutic strategy to protect intestinal barrier function and reduce neuroinflammation in alcohol use disorder: implications for depression and relapse

Abstract

Introduction: Alcohol use disorder (AUD) and major depressive disorder (MDD) are highly comorbid conditions sharing a common neuroinflammatory substrate. Chronic alcohol consumption disrupts the intestinal barrier and induces gut dysbiosis, leading to bacterial lipopolysaccharide (LPS) translocation, systemic inflammation, and central neuroinflammation that persists during abstinence and increases relapse vulnerability. Objective: This perspective review discusses the mechanistic links between alcohol-induced gut barrier dysfunction, neuroinflammation, and neurotransmitter imbalances underlying depression and relapse in AUD, and proposes dietary fiber intake—as a source of intestinal butyrate through microbial fermentation—as a potential adjunct therapeutic strategy. Discussion: Butyrate, the principal short-chain fatty acid produced by colonic fermentation of dietary fiber, is the primary energy substrate of colonocytes and exerts anti-inflammatory effects through inhibition of NF-κB and histone deacetylases. It promotes intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin, claudin-1), reduces LPS translocation, and attenuates the peripheral-to-central inflammatory cascade. By reducing neuroinflammation, butyrate may contribute to restoring the balance of glutamate, dopamine, and serotonin, neurotransmitter systems disrupted by alcohol and critically implicated in depression and relapse. Conclusions: Increasing dietary fiber intake to enhance endogenous butyrate production represents a safe, accessible, and mechanistically grounded strategy to complement existing therapies for AUD-related depression and relapse prevention.