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

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.