Fish-oil supplementation in pregnancy, child metabolomics and asthma risk
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Fish-oil supplementation in pregnancy, child metabolomics and asthma risk. / Rago, Daniela; Rasmussen, Morten A.; Lee-Sarwar, Kathleen A.; Weiss, Scott T.; Lasky-Su, Jessica; Stokholm, Jakob; Bønnelykke, Klaus; Chawes, Bo L.; Bisgaard, Hans.
In: EBioMedicine, Vol. 46, 2019, p. 399-410.Research output: Contribution to journal › Journal article › Research › peer-review
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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
PY - 2019
Y1 - 2019
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.
AB - 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.
KW - Childhood asthma
KW - Fish oil
KW - Metabolomics
U2 - 10.1016/j.ebiom.2019.07.057
DO - 10.1016/j.ebiom.2019.07.057
M3 - Journal article
C2 - 31399385
AN - SCOPUS:85070729446
VL - 46
SP - 399
EP - 410
JO - EBioMedicine
JF - EBioMedicine
SN - 2352-3964
ER -
ID: 228251934