Untargeted Metabolomic Profiling Identifies Disease-specific Signatures in Food Allergy and Asthma.

Abstract

BACKGROUND\nFood allergy (FA) affects an increasing proportion of children. for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed.\n\n\nOBJECTIVE\nTo apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in FA.\n\n\nMETHODS\nMass spectrometry-based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone or both FA and asthma as well as healthy pediatric controls.\n\n\nRESULTS\nIn this pilot study FA subjects exhibited a disease-specific metabolomic signature as compared to both control subjects and asthmatics. In particular, FA was uniquely associated with a marked decrease in sphingolipids, as well as a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T (NKT) cells. Specific comparison of FA and asthmatic subjects revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, history of severe systemic reactions and presence of multiple FA were associated with changes in tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids.\n\n\nCONCLUSIONS\nChildren with FA display a disease-specific metabolomic profile that is informative of disease mechanisms and severity, and which dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in FA children may reflect the interplay between an altered microbiota and immune cell subsets in the gut.