Oxidative Balance Score, Genetic Predictors of the Gut Microbiome, and the Risk of Metabolic-Associated Fatty Liver Disease: A Cohort Study.

Higher oxidative balance score was prospectively associated with lower risk of incident MASLD in a dose-response manner.

• 182,601 UK Biobank participants free of MASLD at baseline were analyzed over a median 10.5 years of follow-up
• 1,500 participants developed incident MASLD during follow-up
• Adjusted HRs (95% CIs) compared with the lowest OBS quartile were 0.82 (0.71–0.94), 0.71 (0.61–0.83), and 0.68 (0.58–0.81) for the second, third, and fourth quartiles
• A significant linear trend was observed across quartiles (p-trend < 0.001)
• OBS was calculated from 16 dietary and 4 lifestyle components reflecting oxidative stress

MASLD genetic risk score was associated with MASLD risk but did not modify the OBS-MASLD association.

• A MASLD genetic risk score (GRS) was constructed and tested as a potential effect modifier
• The MASLD GRS was significantly associated with MASLD risk
• The interaction between MASLD GRS and OBS was not statistically significant (p-interaction > 0.05)
• The association between higher OBS and lower MASLD risk was independent of genetic predisposition to MASLD

Microbial genetic risk scores for Ruminococcus torques and Sutterella were associated with MASLD risk but did not modify the OBS-MASLD association.

• Genetic proxies for gut microbiota composition, specifically Ruminococcus torques and Sutterella, were used to construct microbial GRSs
• Both microbial GRSs were associated with MASLD risk
• Neither microbial GRS significantly modified the OBS-MASLD association (all p-interaction > 0.05)
• The protective association of higher OBS with MASLD was independent of gut microbial genetic predisposition

Incident MASLD cases were identified from hospital and death records in the UK Biobank cohort study design.

• The study used a prospective cohort design with 182,601 participants at baseline
• Participants were free of MASLD at baseline
• Incident MASLD cases were identified from hospital and death records
• Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals
• Median follow-up duration was 10.5 years