Metabolomics-Based Analysis Linking Oxidative Stress-Related Branched-Chain Amino Acid (BCAA) Pathway with Atopic...

Allergic diseases are complex conditions in which oxidative stress contributes to pathogenesis, yet the metabolic mechanisms linking oxidative stress to immunoglobulin E (IgE)-mediated responses remain unclear. This study analyzed 124 children at an 8-year follow-up, identifying those with eczema, rhinitis, and asthma. Oxidative stress markers and ¹H-nuclear magnetic resonance (NMR) blood metabolomic profiles were assessed to determine associations between metabolic pathways and atopic indices. Results showed that glutathione peroxidase (GPx) activity was significantly lower in seafood-sensitized children, while FeNO and mite-specific IgE were elevated in children with rhinitis (p < 0.01). Fractional exhaled nitric oxide (FeNO) correlated positively with allergen-specific IgE and negatively with 8-hydroxy-2'-deoxyguanosine (8-OHdG) (p < 0.01) and rhinitis-related methionine. Furthermore, seafood-specific IgE showed negative correlations with glucose and threonine (p < 0.01). Among 22 metabolites linked to atopy, threonine correlated positively with GPx (p < 0.01), while serine and mannose were associated with total antioxidant capacity (TAC). Pathway analysis revealed that branched-chain amino acid (BCAA) and glycine-serine-threonine metabolism intersected significantly with oxidative stress and atopic indices. In conclusion, a metabolomics-based approach highlights that oxidative stress-related BCAA and threonine pathways are central to the metabolic signature of childhood allergies, providing potential targets for future therapeutic interventions.