한빛사논문
- 조회282
Min Kim MSc, Ph.D 1,2, Nicklas Brustad MD, Ph.D 1, Mina Ali MSc, Ph.D 1, Gözde Gürdeniz MSc, Ph.D 1, Morten Arendt MSc, Ph.D 1,3, Augusto A. Litonjua MD, MPH 4, Craig E. Wheelock PhD 5, Rachel S. Kelly BSc, Ph.D 6, Yulu Chen BSc, Ph.D 6, Nicole Prince BSc, Ph.D 6, Feng Guo MSc, Ph.D 6,7, Xiaobo Zhou MSc, Ph.D 6, Jakob Stokholm MD, Ph.D 1,3, Klaus Bønnelykke MD, Ph.D 1, Scott T. Weiss MD, MS 6, Hans Bisgaard MD, DMSc 1 †, Jessica Lasky-Su ScD 6 ∗, Bo Chawes MD, Ph.D., DMSc 1 ∗
1)COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
2)Faculty of Health and Biomedical Science, University of Surrey, Guildford, U.K
3)Section of Microbiology and Fermentation, Dept of Food Science, University of Copenhagen, Copenhagen, Denmark
4)Division of Pediatric Pulmonary Medicine, Golisano Children’s Hospital, University of Rochester Medical Center, Rochester, NY, United States
5)Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, 171 76, Stockholm, Sweden; Gunma Initiative for Advanced Research (GIAR), Gunma University, Maebashi, Japan
6)Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
7)Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
Correspondence: Professor Bo Chawes, MD, PhD, DMSc
†Died September 8th, 2022.
∗Contributed equally.
Abstract
Background: Gestational vitamin D deficiency is implicated in development of respiratory diseases in the offspring, but the mechanism underlying this relationship is unknown.
Objectives: To study the link between gestational vitamin D exposure and childhood asthma phenotypes using maternal blood metabolomics profiling.
Methods: Untargeted blood metabolomic profiles were acquired using liquid chromatography-mass spectrometry at one week postpartum from 672 women in the COPSAC2010 mother-child cohort, and at pregnancy week 32-38 from 779 women in the VDAART mother-child cohort. In COPSAC2010, we employed multivariate models and pathway-enrichment analysis to identify metabolites and pathways associated with gestational vitamin D blood levels and investigated their relationship with development of asthma phenotypes in early childhood. The findings were validated in VDAART and in cellular models.
Results: In COPSAC2010, higher vitamin D blood levels at one week postpartum were associated with distinct maternal metabolome perturbations with significant enrichment of the sphingomyelin pathway (p<.01). This vitamin D-related maternal metabolic profile at one week postpartum containing 46 metabolites was associated with decreased risk of recurrent wheeze (Hazard Ratio (HR)=0.92 [95% CI, 0.86-0.98], p=.01) and wheeze exacerbations (HR=0.90 [0.84-0.97], p=.01) at age 0-3 years. The same metabolic profile was similarly associated with decreased risk of asthma/wheeze at age 0-3 in VDAART (OR=0.92 [0.85-0.99], p=0.04). Human bronchial epithelial cells treated with high-dose vitamin D3 showed an increased cytoplasmatic sphingolipid level (p<0.01).
Conclusion: This exploratory metabolomics study in two independent birth cohorts demonstrates that the beneficial effect of higher gestational vitamin D exposure on offspring respiratory health is characterized by specific maternal metabolic alterations during pregnancy, which involves the sphingomyelin pathway.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-11-09)
- 국외 연구진
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