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

The oxidative balance score (OBS) integrates dietary and lifestyle factors to reflect oxidative stress. OBS has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the modifying roles of genetic predisposition and gut microbiota remain unclear. This study evaluated the prospective association between OBS and MASLD and potential modification by genetic and microbial factors. We analyzed 182 601 UK Biobank participants free of MASLD at baseline. OBS was calculated from 16 dietary and 4 lifestyle components. Incident MASLD cases were identified from hospital and death records. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). During a median 10.5 years of follow-up, 1500 participants developed MASLD. Compared with the lowest OBS quartile, adjusted HRs (95% CIs) 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 (p-trend < 0.001). MASLD genetic risk score (GRS) and microbial GRSs for Ruminococcus torques and Sutterella were associated with MASLD risk but did not modify the OBS-MASLD association (all p-interaction > 0.05). Higher OBS was associated with lower MASLD risk, independent of genetic and microbial GRSs. These findings provide prospective association evidence that may inform future intervention studies.