Targeting the Microbiome to Treat Alcohol Use Disorder and Liver Disease

Alcohol use disorder and alcohol-associated liver disease represent a global health burden, yet treatment options remain limited. Emerging evidence has shown the intestinal microbiome to be a mediator of alcohol-associated organ injury, establishing gut dysbiosis, intestinal barrier dysfunction, and aberrant microbial metabolite production as drivers of disease. The gut-liver-brain axis provides a mechanistic framework in which microbial products and signals fuel hepatic inflammation, steatosis, fibrosis, and neuroinflammation that drive alcohol consumption. This review discusses current evidence on how chronic alcohol exposure shapes microbial communities, disrupts the gut epithelium, and alters innate immune and metabolic circuits in the liver and the brain. We examine how microbiome-targeted interventions, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, non-absorbable antibiotics, and short-chain fatty acid supplementation, can act on mechanistic targets along this axis. Finally, we highlight knowledge gaps, including the roles of causal microbial taxa, sex differences in gut-immune-brain signaling, and windows of reversibility that must be further investigated and understood to translate microbial modulation into effective therapies. In conclusion, this review summarizes the current literature on targeting the microbiome and the gut-liver-brain axis as a treatment approach, with a focus on the mechanisms within this axis and the interventions that target them.