Study links ultra-processed foods to Crohn's disease through missing omega-3
Researchers identified how ultra-processed foods increase Crohn's disease risk: they deplete protective omega-3 fatty acids in the blood. The finding, validated across UK and Chinese populations, could reshape food industry reformulation strategies and dietary guidelines for inflammatory bowel disease prevention.
Originaltitel: Integrated metabolomics and genetic analyses reveal loss of protective docosahexaenoic acid as a key driver linking ultra-processed food to Crohn’s disease risk
Abstract Objectives To characterize ultra-processed food (UPF) circulating metabolic signatures associated with Crohn’s disease (CD) and to localize key metabolic mediators linking UPF intake to CD risk. Design Prospective cohort study. Setting Two large multi-center cohorts (UK Biobank [UKB] and Whitehall II [WHII] study) across the UK and an Eastern multi-center cohort ONE-IBD Study from China. Participants UK Biobank discovery cohort (n=10,229) for signature derivation, internal validation cohort (n=91,306), external validation cohort Whitehall-II (n=7,893), and three additional cohorts (two Western and ONE-IBD) for validation of key metabolic drivers. Main outcome measures Primary outcomes were UPF-related circulating metabolic signatures and their associations with CD risk; secondary outcomes included evidence supporting causal roles of candidate metabolites and genetic pathways assessed by Mendelian randomization, colocalization, and gene-environment analysis. Results A UPF metabolic signature of 73 metabolites was constructed and validated across cohorts (Spearman ρ: 0.20-0.25). More pronounced UPF metabolic signature was associated with increased CD risk (HR per SD =2.65, 95% CI 1.57-4.48). WGCNA revealed a cluster enriched in fatty acids. Within this cluster, docosahexaenoic acid (DHA) emerged as the strongest, which mediated 17.1% of the UPF-CD association. External validation in ONE-IBD supported DHA as the strongest associated metabolite with UPF and CD. Mendelian randomization supported a causal protective effect of DHA on CD (OR=0.72, 95% CI 0.61– 0.83; P<0.001), with colocalization implicating rs174546 in the FADS1 gene. Conclusion The adverse effects of UPF on CD risk may be driven by a relative deficiency of protective metabolites such as DHA, apart from additive harm to metabolic depletion. This reframes UPF-related risk and highlighting potential targets for precision nutrition in CD prevention.