Metabolomic and Proteomic Signatures of Ultra-processed Foods Are Positively Associated with Adverse Liver Outcomes

Higher ultra-processed foods consumption is associated with increased risk of obesity and type 2 diabetes; however, evidence is sparse on liver diseases and the underlying mechanisms remain limited. To evaluate associations between metabolomic and proteomic signatures of ultra-processed food intake and adverse liver outcomes.173,840 participants aged 40-69 years from the UK Biobank were analyzed. Ultra-processed food intake was assessed using multiple 24-hour dietary recalls. Plasma metabolites were measured using nuclear magnetic resonance spectroscopy, and plasma proteome was profiled using the Olink platform. Adverse liver outcomes (metabolic dysfunction-associated steatotic liver disease [MASLD], cirrhosis, liver cancer, and severe liver disease) were ascertained using data from the in-hospital records, or cancer or death registry. We used elastic net regression to calculate omics signatures of ultra-processed foods and Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for ultra-processed foods and their omics signatures and adverse liver outcomes, adjusting for multiple potential confounding factors. With a median of 8.9 years’ follow-up, an increase of 1 standard deviation (SD) in metabolic signature score of ultra-processed foods was associated with increased risk of MASLD (HR 1.61; 95% CI 1.38-1.87). An increase of 1 SD in proteomic signature score of ultra-processed foods was associated with increased risk of MASLD (HR 1.84; 95% CI 1.45-2.35), cirrhosis (HR 1.49; 95% CI 1.16-1.91), and severe liver disease (HR 1.48; 95% CI 1.07-2.03). 34 metabolites and 65 proteins were significantly associated with ultra-processed food intake and were enriched in biological pathways such as lipid metabolism, oxidative stress, and inflammatory response. More than half of these metabolites and proteins are significantly associated with the risk of MASLD and cirrhosis. Ultra-processed food intake and its metabolic and proteomic signatures are positively associated with the risk of MASLD.