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Published on: August 7, 2017
Plasma metabolomics in infancy reveals early signatures of a stringently-defined otitis-prone phenotype
Nicole Prince1,2, Jing Chen3,4, Ravinder Kaur5
1Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Insights
Infant metabolomic profiles reveal distinct biochemical signatures in children prone to recurrent ear infections (otitis media). Lower levels of certain lipids and amino acids in infancy may predict otitis proneness.
Area of Science:
- Pediatric immunology and metabolomics
- Biochemical pathways in early childhood disease
- Longitudinal cohort studies in otitis media
Background:
- Otitis media (ear infections) is common in early life, but factors predisposing children to recurrent cases are unclear.
- Metabolomics can identify biochemical changes linked to disease susceptibility.
- This study investigated infant plasma metabolomic profiles and their association with otitis proneness.
Purpose of the Study:
- To determine if longitudinal infant plasma metabolomic profiles are associated with the development of recurrent acute otitis media (AOM).
- To identify specific metabolic pathways and biomarkers related to otitis proneness in early childhood.
Main Methods:
- Plasma samples from the Rochester Combined Cohort (RCC) were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) between 6 and 18 months of age.
- Children were classified as otitis prone (sOP) if they had ≥3 AOM episodes in 6 months or ≥4 in 12 months (tympanocentesis-confirmed).
- Generalized additive mixed models (GAMMs) compared metabolite levels between sOP and non-otitis-prone (nOP) children, adjusting for confounders.
Main Results:
- sOP children showed consistently lower metabolite trajectories in lipid and amino acid pathways compared to nOP children.
- Significantly lower levels of 16 metabolites involved in inflammatory lipid signaling, redox, and fatty acid metabolism were found in sOP infants (p < 4.4 × 10⁻⁴).
- Elevated levels of glycerophosphoinositol were observed in sOP infants (p = 2.9 × 10⁻⁴).
Conclusions:
- Distinct plasma metabolomic signatures in infancy precede the development of recurrent otitis media.
- Altered immune-metabolic programming may underlie susceptibility to otitis media.
- Longitudinal metabolomics is a valuable approach for uncovering biochemical mechanisms of otitis proneness.
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.
