Fish-oil supplementation in pregnancy, child metabolomics and asthma risk.
Asthma
/ epidemiology
Biomarkers
Child, Preschool
Chromatography, Liquid
Dietary Supplements
Female
Fish Oils
/ administration & dosage
Follow-Up Studies
Humans
Infant
Kaplan-Meier Estimate
Mass Spectrometry
Maternal Exposure
Metabolome
Metabolomics
Pregnancy
Prenatal Exposure Delayed Effects
Risk Assessment
Risk Factors
Childhood asthma
Fish oil
Metabolomics
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
17
05
2019
revised:
22
07
2019
accepted:
22
07
2019
pubmed:
11
8
2019
medline:
16
1
2020
entrez:
11
8
2019
Statut:
ppublish
Résumé
We recently demonstrated that maternal dietary supplementation with fish oil-derived n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy reduces the risk of asthma in the offspring but the mechanisms involved are unknown. Here we investigated potential metabolic mechanisms using untargeted liquid chromatography-mass spectrometry-based metabolomics on 577 plasma samples collected at age 6 months in the offspring of mothers participating in the n-3 LCPUFA randomized controlled trial. First, associations between the n-3 LCPUFA supplementation groups and child metabolite levels were investigated using univariate regression models and data-driven partial least square discriminant analyses (PLS-DA). Second, we analyzed the association between the n-3 LCPUFA metabolomic profile and asthma development using Cox-regression. Third, we conducted mediation analyses to investigate whether the protective effect of n-3 LCPUFA on asthma was mediated via the metabolome. The univariate analyses and the PLS-DA showed that maternal fish oil supplementation affected the child's metabolome, especially with lower levels of the n-6 LCPUFA pathway-related metabolites and saturated and monounsaturated long-chain fatty acids-containing compounds, lower levels of metabolites of the tryptophan pathway, and higher levels of metabolites in the tyrosine and glutamic acid pathway. This fish oil-related metabolic profile at age 6 months was significantly associated with a reduced risk of asthma by age 5 and the metabolic profile explained 24% of the observed asthma-protective effect in the mediation analysis. Several of the observed pathways may be involved in the asthma-protective effect of maternal n-3 LCPUFA supplementation and act as mediators between the intervention and disease development. COPSAC is funded by private and public research funds all listed on www.copsac.com.
Sections du résumé
BACKGROUND
BACKGROUND
We recently demonstrated that maternal dietary supplementation with fish oil-derived n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy reduces the risk of asthma in the offspring but the mechanisms involved are unknown.
METHODS
METHODS
Here we investigated potential metabolic mechanisms using untargeted liquid chromatography-mass spectrometry-based metabolomics on 577 plasma samples collected at age 6 months in the offspring of mothers participating in the n-3 LCPUFA randomized controlled trial. First, associations between the n-3 LCPUFA supplementation groups and child metabolite levels were investigated using univariate regression models and data-driven partial least square discriminant analyses (PLS-DA). Second, we analyzed the association between the n-3 LCPUFA metabolomic profile and asthma development using Cox-regression. Third, we conducted mediation analyses to investigate whether the protective effect of n-3 LCPUFA on asthma was mediated via the metabolome.
FINDINGS
RESULTS
The univariate analyses and the PLS-DA showed that maternal fish oil supplementation affected the child's metabolome, especially with lower levels of the n-6 LCPUFA pathway-related metabolites and saturated and monounsaturated long-chain fatty acids-containing compounds, lower levels of metabolites of the tryptophan pathway, and higher levels of metabolites in the tyrosine and glutamic acid pathway. This fish oil-related metabolic profile at age 6 months was significantly associated with a reduced risk of asthma by age 5 and the metabolic profile explained 24% of the observed asthma-protective effect in the mediation analysis.
INTERPRETATION
CONCLUSIONS
Several of the observed pathways may be involved in the asthma-protective effect of maternal n-3 LCPUFA supplementation and act as mediators between the intervention and disease development.
FUNDING
BACKGROUND
COPSAC is funded by private and public research funds all listed on www.copsac.com.
Identifiants
pubmed: 31399385
pii: S2352-3964(19)30499-2
doi: 10.1016/j.ebiom.2019.07.057
pmc: PMC6712349
pii:
doi:
Substances chimiques
Biomarkers
0
Fish Oils
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
399-410Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL123915
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141826
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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