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EBioMedicine. 2019 Aug 6. pii: S2352-3964(19)30499-2. doi: 10.1016/j.ebiom.2019.07.057. [Epub ahead of print]

Fish-oil supplementation in pregnancy, child metabolomics and asthma risk.

Author information

1
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
2
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Food Science, University of Copenhagen, Copenhagen, Denmark.
3
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
4
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Pediatrics, Slagelse Hospital, Slagelse, Denmark.
5
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: chawes@copsac.com.
6
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: bisgaard@copsac.com.

Abstract

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:

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:

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:

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:

COPSAC is funded by private and public research funds all listed on www.copsac.com.

KEYWORDS:

Childhood asthma; Fish oil; Metabolomics

PMID:
31399385
DOI:
10.1016/j.ebiom.2019.07.057
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