Is light-to-moderate alcohol drinking associated with the onset of metabolic dysfunction-associated steatotic liver disease in a Chinese cohort?

BACKGROUND: The association between light-to-moderate alcohol drinking (≤14 g/d for females; ≤28 g/d for males) and the risk of steatotic liver disease (SLD), including its metabolic dysfunction-associated subtype (MASLD), remains unclear, as does the role of related gut microbiota.

OBJECTIVES: We investigated the association between light-to-moderate alcohol drinking and incident SLD/MASLD, identified gut microbial species associated with such drinking, and evaluated their associations with disease risk.

METHODS: Among 1297 adults from a Chinese community-based cohort, alcohol intake was assessed by a validated questionnaire, and SLD was diagnosed by vibration-controlled transient elastography. In a subset with fecal samples at follow-up (n = 665), gut microbiota was profiled using shotgun metagenomic sequencing. We used the average alcohol intake from baseline and follow-up to represent long-term drinking habits. Species differentially associated with alcohol intake were identified using zero-inflated Gaussian models with false discovery rate (FDR) correction. Cox and logistic regression were used to estimate hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), respectively.

RESULTS: During follow-up (2020-2025), 513 incident SLD cases were identified. Light-to-moderate drinkers showed higher risks of SLD (HR = 1.27, 95% CI: 1.03, 1.58) and MASLD (HR = 1.27, 95% CI: 1.01, 1.59) compared with abstainers. For the same comparison, liquor consumption was positively associated with SLD (HR = 1.29, 95% CI: 1.01, 1.65). We identified 89 microbial species associated with alcohol intake and constructed a microbial score, which was positively associated with SLD (OR(T3 vs T1) = 1.54, 95% CI: 1.03, 2.31, P(trend) = 0.05) and MASLD (OR(T3 vs T1) = 1.50, 95% CI: 1.00, 2.26, P(trend) = 0.05). Among these species, Stenotrophomonas maltophilia AQ, Olsenella E timonensis, and Firm 11 sp., which were less abundant in drinkers, showed inverse associations with both conditions after FDR correction.

CONCLUSIONS: Light-to-moderate alcohol consumption was associated with increased risks of SLD and MASLD. A gut microbial score based on alcohol-associated species also predicted higher disease risk.