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Fish-oil supplementation in pregnancy, child metabolomics and asthma risk.
EBioMedicine. 2019 Aug; 46:399-410.E

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31399385

Citation

Rago, Daniela, et al. "Fish-oil Supplementation in Pregnancy, Child Metabolomics and Asthma Risk." EBioMedicine, vol. 46, 2019, pp. 399-410.
Rago D, Rasmussen MA, Lee-Sarwar KA, et al. Fish-oil supplementation in pregnancy, child metabolomics and asthma risk. EBioMedicine. 2019;46:399-410.
Rago, D., Rasmussen, M. A., Lee-Sarwar, K. A., Weiss, S. T., Lasky-Su, J., Stokholm, J., Bønnelykke, K., Chawes, B. L., & Bisgaard, H. (2019). Fish-oil supplementation in pregnancy, child metabolomics and asthma risk. EBioMedicine, 46, 399-410. https://doi.org/10.1016/j.ebiom.2019.07.057
Rago D, et al. Fish-oil Supplementation in Pregnancy, Child Metabolomics and Asthma Risk. EBioMedicine. 2019;46:399-410. PubMed PMID: 31399385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fish-oil supplementation in pregnancy, child metabolomics and asthma risk. AU - Rago,Daniela, AU - Rasmussen,Morten A, AU - Lee-Sarwar,Kathleen A, AU - Weiss,Scott T, AU - Lasky-Su,Jessica, AU - Stokholm,Jakob, AU - Bønnelykke,Klaus, AU - Chawes,Bo L, AU - Bisgaard,Hans, Y1 - 2019/08/06/ PY - 2019/05/17/received PY - 2019/07/22/revised PY - 2019/07/22/accepted PY - 2019/8/11/pubmed PY - 2020/1/16/medline PY - 2019/8/11/entrez KW - Childhood asthma KW - Fish oil KW - Metabolomics SP - 399 EP - 410 JF - EBioMedicine JO - EBioMedicine VL - 46 N2 - 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. SN - 2352-3964 UR - https://www.unboundmedicine.com/medline/citation/31399385/Fish_oil_supplementation_in_pregnancy_child_metabolomics_and_asthma_risk_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3964(19)30499-2 DB - PRIME DP - Unbound Medicine ER -