Causal relationship between fatty acid metabolism and allergic asthma: a mendelian randomization and multi-omics study

Allergic asthma (AAS) arises from intricate gene-environment interactions, yet its pathophysiological mechanisms remain incompletely understood. This study employs a multi-omics approach to elucidate the regulatory role of metabolites in AAS pathogenesis, aiming to identify novel therapeutic targets and preventive strategies. We conducted bidirectional two-sample Mendelian randomization (MR) analysis on 1,400 serum metabolites, followed by co-localization analysis to validate shared genetic loci. Metabolic pathway enrichment focusing on rate-limiting enzymes was performed, complemented by protein-protein interaction (PPI) network construction. MR was systematically applied to assess the impact of 17 lifestyle factors on AAS-associated metabolites. Six metabolites including Carnitine C14 (OR = 2.660) and 3-hydroxyoleoylcarnitine (OR = 1.620) showed significant associations with AAS after false discovery rate (FDR) correction (FDR 0.9) identified fatty acid metabolism as the central pathway, with ACACB demonstrating significant interaction with salbutamol’s target ADRB3. Lifestyle modulation analysis revealed cereal intake suppressed Carnitine C14 metabolism (p = 0.007), while cheese (p = 0.029) and oily fish consumption (p = 0.015) regulated 3-hydroxyoleoylcarnitine levels. This multi-omics integration study pioneers in delineating fatty acid metabolic reprogramming as a central mechanism in AAS pathogenesis. The identified ACACB-ADRB3 axis presents a novel therapeutic target, while dietary modulations of metabolite profiles offer promising avenues for personalized prevention strategies, advancing precision medicine in asthma management.