Metabolomic Analysis Reveals Distinct Profiles in the Plasma and Urine Associated with IgE Reactions in Childhood Asthma

Abstract

Several metabolomics studies have identified altered metabolic pathways that are related to asthma. However, an integrative analysis of the metabolic responses across blood and urine for a comprehensive framework of asthma in early childhood remains lacking. Fifty-four age-matched children with asthma (n = 28) and healthy controls (n = 26) were enrolled. Metabolome analysis of the plasma and urine samples was performed using ¹H-nuclear magnetic resonance (NMR) spectroscopy coupled with partial least-squares discriminant analysis (PLS-DA). Integrated analysis of blood and urine metabolic profiling related to IgE reactions for childhood asthma was investigated. A significantly higher plasma histidine level was found, in parallel with lower urinary 1-methylnicotinamide and trimethylamine N-oxide (TMAO) levels, in children with asthma compared to healthy controls. Compared to children without allergic sensitization, 11 (92%) plasma metabolites and 8 (80%) urinary metabolites were found to be significantly different in children with IgE and food sensitization respectively. There were significant correlations between the plasma 3-hydroxybutyric acid and excreted volumes of the hydroxy acids, which were strongly correlated to plasma leucine and valine levels. Urine N-phenylacetylglycine, a microbial-host co-metabolite, was strongly correlated with total serum and food allergen-specific IgE levels. Plasma pyruvate and urine valine, leucine, and isoleucine degradation metabolisms were significantly associated with allergic sensitization for childhood asthma. In conclusion, blood and urine metabolome reflect different metabolic pathways in allergic reactions. Plasma pyruvate metabolism to acetic acid appears to be associated with serum IgE production, whereas urine branched-chain amino acid metabolism primarily reflects food allergic reactions against allergies.