Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026
Plasma metabolomics in infancy reveals early signatures of a stringently-defined otitis-prone phenotype.
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Prince Nicole, Chen Jing, Kaur Ravinder, Syphurs Caitlin, Hoch Annmarie, Angelidou Asimenia, McEnaney Kerry, Chawes Bo, Bæk Ole, Wang Tingting, Brustad Nicklas, Levy Ofer, Diray-Arce Joann, Pichichero Michael, Lasky-Su Jessica A, IDEaL Consortium
Аннотация
BACKGROUND: Otitis media is highly prevalent during early life, yet the molecular factors that predispose children to recurrent episodes are poorly defined. Metabolomics captures dynamic biochemical changes and may help identify pathways influencing otitis susceptibility. We examined whether longitudinal infant plasma metabolomic profiles were associated with development of stringently-defined otitis proneness in the Rochester Combined Cohort (RCC; Rochester, NY).
METHODS: Global plasma metabolomic profiling was performed in RCC samples collected between ~6 and 18 months of age using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Children were classified as stringently-defined otitis prone (sOP) if they experienced ≥3 acute otitis media (AOM) episodes within a 6-month period or ≥4 AOM episodes within a 12-month period during the first 3 years of life; all AOM episodes were tympanocentesis-confirmed. Generalized additive mixed models (GAMMs) assessed age-dependent differences in plasma metabolite levels between sOP and non-otitis-prone (nOP) children, adjusting for potential confounders.
RESULTS: Several metabolites demonstrated age-related declines in lipid and amino acid pathways, with consistently lower metabolite trajectories in the sOP group. Compared with nOP children, sOP children exhibited significantly lower levels of 16 metabolites related to inflammatory lipid signaling, redox metabolism, and fatty acid metabolism (p < 4.4 × 10-4) and higher levels of glycerophosphoinositol (p = 2.9 × 10-4). These findings were directionally consistent in a sensitivity analysis additionally adjusted for recent antibiotic use.
CONCLUSION: Children who subsequently met sOP criteria by age 3 years exhibited distinct plasma metabolomic signatures during infancy, suggesting altered immune-metabolic programming preceding recurrent otitis media. Longitudinal metabolomics provides a promising framework to identify biochemical mechanisms underlying otitis proneness.
METHODS: Global plasma metabolomic profiling was performed in RCC samples collected between ~6 and 18 months of age using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Children were classified as stringently-defined otitis prone (sOP) if they experienced ≥3 acute otitis media (AOM) episodes within a 6-month period or ≥4 AOM episodes within a 12-month period during the first 3 years of life; all AOM episodes were tympanocentesis-confirmed. Generalized additive mixed models (GAMMs) assessed age-dependent differences in plasma metabolite levels between sOP and non-otitis-prone (nOP) children, adjusting for potential confounders.
RESULTS: Several metabolites demonstrated age-related declines in lipid and amino acid pathways, with consistently lower metabolite trajectories in the sOP group. Compared with nOP children, sOP children exhibited significantly lower levels of 16 metabolites related to inflammatory lipid signaling, redox metabolism, and fatty acid metabolism (p < 4.4 × 10-4) and higher levels of glycerophosphoinositol (p = 2.9 × 10-4). These findings were directionally consistent in a sensitivity analysis additionally adjusted for recent antibiotic use.
CONCLUSION: Children who subsequently met sOP criteria by age 3 years exhibited distinct plasma metabolomic signatures during infancy, suggesting altered immune-metabolic programming preceding recurrent otitis media. Longitudinal metabolomics provides a promising framework to identify biochemical mechanisms underlying otitis proneness.