Alcohol, aging, and the gut microbiome: Intersections of immunity, barrier dysfunction, and disease
Year: 2025
Type: review
Abstract: Alcohol consumption exerts complex, dose- and context-dependent effects on human health, particularly by influencing the gut microbiome, intestinal barrier integrity, immune regulation, and aging processes. Genetic variation and advancing age are two major, and often interacting, factors that modify the risk of alcohol-related diseases. Among genetic factors, the prevalent aldehyde dehydrogenase 2 polymorphism (ALDH2∗2) compromises acetaldehyde clearance, driving toxic metabolite accumulation, oxidative stress, and increased intestinal permeability that disrupts gut microbial communities, even at low levels of alcohol consumption. Heavy and chronic alcohol use further disrupts gut microbial communities, erodes mucosal integrity, and drives systemic inflammation, contributing to alcohol-associated liver disease (ALD), neuroinflammation, and multi-organ injury. Aging independently worsens these effects by promoting chronic low-grade inflammation and impaired immune responses, heightening susceptibility to alcohol-induced pathology. In specific contexts, such as certain autoimmune diseases, low to moderate alcohol intake may exert immunomodulatory effects and influence the gut microbiome, potentially contributing to reduced inflammation and alterations in microbial composition. This review synthesizes current mechanistic insights into how alcohol, host genetics, the gut microbiome, immune regulatory pathways, and aging intersect to influence disease risk. As global populations age and the burden of alcohol-related health issues rises, there is an urgent need for integrated, systems-level approaches. Future research should prioritize precision-based, gut-targeted strategies aimed at restoring microbial balance, maintaining intestinal barrier integrity, and mitigating alcohol-related harm across the lifespan.
Source: Alcohol
Institutions: The University of Texas at Austin, National Institute on Alcohol Abuse and Alcoholism, Richard L. Roudebush VA Medical Center, Indiana University Indianapolis, Indiana University School of Medicine, National Institutes of Health, National Institutes of Health Clinical Center, University of Colorado Anschutz, University of Colorado Denver, University of California San Diego
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,720
Funders: U.S. Department of Veterans Affairs, Department of Veterans' Affairs, Australian Government, National Institutes of Health, University of California, San Diego, School of Medicine, Indiana University, Dell Medical School, University of Texas at Austin, National Institute on Alcohol Abuse and Alcoholism, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH Clinical Center
Awards: G1900370045, G2078522666, The role of intestinal gp130 in alcohol-associated liver disease, G4015128100, G4230513806, G479491994, G550647324, G6290609879, Resource-based Center for the study of the joint microenvironment in rheumatology (Overall Application), G7688022655, Novel animal models to study miRNA-mediated alcoholic liver disease, Immunological Profiles and prognostic outcomes in patients with alcoholic hepatitis, G9000242574, San Diego Digestive Diseases Research Center, Southern California Research Center for ALPD and Cirrhosis, FKBP5 in the pathogenesis of alcohol-associated liver disease, Neuroinflammatory GeroMiRs and Alcohol: Defining Mechanisms of ADRD, Goblet cells and intestinal immune response in alcohol-associated liver disease
OpenAlex ID: W4412391947