Effects of Chronic Moderate Alcohol Intake on Metabolic Phenotypes and Gut Microbiota in Lean and Obese Mice with Distinct Dietary Structures.

BACKGROUND

The 2023 Delphi consensus defined metabolic and alcohol-associated liver disease (MetALD), distinguishing between alcohol abuse and moderate consumption. Although alcohol abuse is known to accelerate fatty liver disease progression, the health effects of chronic moderate alcohol intake under different dietary conditions remain unclear. This study aimed to evaluate the impact of moderate alcohol consumption on metabolic phenotypes and gut microbiota/metabolites in lean and obese mice and to propose a model approximating MetALD features.

METHODS

C57BL/6J mice were fed either a low-fat diet (LFD) or a high-fat diet (HFD) for 12 weeks, with access to 10% (v/v) alcohol in drinking water. Systemic metabolic parameters, liver histopathology, inflammatory and fibrotic markers, gut microbiota composition, and the fecal metabolome were assessed.

RESULTS

In LFD-fed mice, 10% alcohol intake induced multiple metabolic alterations, including elevated serum triglycerides, reduced fasting blood glucose, and changes in hepatic lipid metabolism along with steatosis and inflammation-though further studies are required to confirm causality. When combined with HFD, alcohol did not significantly exacerbate most glucose/lipid metabolic disorders but markedly increased hepatic inflammatory cell infiltration and fibrosis progression. Alcohol consistently increased gut microbial α-diversity in both dietary groups, while downregulating beneficial metabolites such as amino acids (e.g., glutamine, histidine), their derivatives, and short-chain fatty acids. Correlation analyses associated these microbial and metabolic changes with altered amino acid/cholesterol metabolism and inflammatory/fibrotic phenotypes, particularly under HFD conditions.

CONCLUSIONS

These findings suggest that chronic moderate alcohol intake presents distinct risks in lean and obese individuals with different dietary structures.