Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort

Abstract

BackgroundThere are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations. ObjectiveTo identify metabolites which are unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort (the Boston Birth Cohort). MethodsMass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (N=811). FA was diagnosed based on clinical symptoms consistent with an acute hypersensitivity reaction upon food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined based on physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders. ResultsDuring a median follow-up of 11.8±5.2 years from birth, 78 children developed FA and 171 developed asthma. Androgenic and pregnenolone steroids were significantly associated with a lower risk of FA, especially for egg allergy. N,N,N-trimethyl-5-aminovalerate (OR=0.65, 95%CI=0.48-0.87) and 1-Oleoyl-2-arachidonoyl-sn-glycero-3-phosphoinositol (OR=0.77, 95%CI=0.66-0.90) were inversely associated with FA risk. Orotidine (OR=4.73, 95%CI=2.2-10.2) and 4-cholesten-3-one (OR=0.52, 95%CI=0.35-0.77) were the top two metabolites associated with risk of asthma, although they had no association with FA. In comparison, children with both FA and asthma exhibited an altered metabolomic profile that aligned with that of FA, including altered levels of lipids and steroids. ConclusionIn this U.S. multi-ethnic prospective birth cohort, unique and shared alterations in plasma metabolites during early childhood were associated with risk of developing FA, asthma, or both. These findings await further validation.