Role of L-Arginine in the Gut-Liver Axis: Mediating Ethanol's Alterations in Fat Dynamics and Oxidative Stress

Chronic ethanol exposure disrupts the gut-liver axis, promoting oxidative stress and hepatic steatosis that contribute to alcohol-associated liver disease (ALD). L-arginine is a conditionally essential amino acid with potential roles in redox regulation and host-microbiota interactions. Using a chronic Lieber-DeCarli ethanol feeding model in female mice, we found that dietary arginine supplementation preserved body weight and fat mass, reduced hepatic triglyceride accumulation, and attenuated oxidative stress. These effects were associated with favorable changes in gut microbiota composition, microbial metabolic pathways, and intestinal barrier integrity. Together, our findings support arginine supplementation as a potential nutritional strategy to mitigate ethanol-induced gut-liver axis dysfunction.