Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma.
Asthma
food allergy
invariant natural killer T cells
metabolites
metabolomics
secondary bile acids
sphingolipids
tryptophan
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
11
06
2019
revised:
10
09
2019
accepted:
01
10
2019
pubmed:
2
11
2019
medline:
1
12
2020
entrez:
1
11
2019
Statut:
ppublish
Résumé
Food allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed. We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA. Mass 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 control subjects. In this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. In particular, FA was uniquely associated with a marked decrease in sphingolipid levels, as well as levels of a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T cells. Specific comparison of patients with FA and asthmatic patients 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, the history of severe systemic reactions and the presence of multiple FAs were associated with changes in levels of tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids. Children with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in children with FA might reflect the interplay between an altered microbiota and immune cell subsets in the gut.
Sections du résumé
BACKGROUND
Food allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed.
OBJECTIVE
We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA.
METHODS
Mass 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 control subjects.
RESULTS
In this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. In particular, FA was uniquely associated with a marked decrease in sphingolipid levels, as well as levels of a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T cells. Specific comparison of patients with FA and asthmatic patients 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, the history of severe systemic reactions and the presence of multiple FAs were associated with changes in levels of tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids.
CONCLUSIONS
Children with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in children with FA might reflect the interplay between an altered microbiota and immune cell subsets in the gut.
Identifiants
pubmed: 31669435
pii: S0091-6749(19)31402-2
doi: 10.1016/j.jaci.2019.10.014
pmc: PMC7062570
mid: NIHMS1542349
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
897-906Subventions
Organisme : NIAID NIH HHS
ID : R01 AI065617
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI126915
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI132843
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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