Dietary pattern modifies the risk of MASLD through metabolomic signature

Background & Aims The EAT-Lancet Commission in 2019 advocated a plant-centric diet for health and environmental benefits, but its relation to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to discover the metabolite profile linked to the EAT-Lancet diet and its association with MASLD risk, considering genetic predisposition. Methods We analyzed data from 105,752 UK Biobank participants with detailed dietary and metabolomic information. We constructed an EAT-Lancet diet index and derived a corresponding metabolomic signature through elastic net regression. A weighted polygenic risk score for MASLD was computed from associated risk variants. The Cox proportional hazards model was employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of MASLD (defined as hospital admission or death). Results During a median follow-up period of 11.6 years, 1,138 cases of MASLD were documented. The multivariable HR (95% CI) of MASLD for the highest versus the lowest group for the EAT-Lancet diet index was 0.79 (0.66, 0.95). The diet's impact was unaffected by genetic predisposition to MASLD (P = 0.42). Moreover, a robust correlation was found between the metabolomic signature and the EAT-Lancet diet index (Pearson r = 0.29; P <0.0001). Participants with the highest group for the metabolomic signature showing a multivariable HR (95% CI) of 0.46 (0.37, 0.58) for MASLD, in comparison to those with the lowest group. Conclusions Higher intake of the EAT-Lancet diet and its associated metabolite signature are both linked to a reduced risk of MASLD, independently of traditional risk factors. Impact and implications Our analysis leveraging the UK Biobank study showed higher adherence to the EAT-Lancet diet was associated with a reduced risk of MASLD. We identified a unique metabolite signature comprising 81 metabolites associated with the EAT-Lancet diet, potentially underlying the diet's protective mechanism against MASLD. These findings suggest the EAT-Lancet diet may offer substantial protective benefits against MASLD.