期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 146, 期 6, 页码 1358-1366出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2020.07.005
关键词
Allergic rhinitis; microbiota; DNA methylation; gene expression; early life; upper airways
资金
- National Institutes of Health (NIH) [HL129735]
- Lundbeck Foundation [R16-A1694]
- Danish Ministry of Health [903516]
- Danish Council for Strategic Research [0603-00280B]
- Danish Council for Independent Research [10-082884, 271-08-0815]
- Capital Region Research Foundation
- Bourse de formation postdoctorale - Fonds de recherche du Quebec - Sante
- NIH [AI133765, AI144722]
- Novo Nordisk Fonden
Background: The upper airways present a barrier to inhaled allergens and microbes, which alter immune responses and subsequent risk for diseases, such as allergic rhinitis (AR). Objective: We tested the hypothesis that early-life microbial exposures leave a lasting signature in DNA methylation that ultimately influences the development of AR in children. Methods: We studied upper airway microbiota at 1 week, 1 month, and 3 months of life, and measured DNA methylation and gene expression profiles in upper airway mucosal cells and assessed AR at age 6 years in children in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort. Results: We identified 956 AR-associated differentially methylated CpGs in upper airway mucosal cells at age 6 years, 792 of which formed 3 modules of correlated differentially methylated CpGs. The eigenvector of 1 module was correlated with the expression of genes enriched for lysosome and bacterial invasion of epithelial cell pathways. Early-life microbial diversity was lower at 1 week (richness P = .0079) in children with AR at age 6 years, and reduced diversity at 1 week was also correlated with the same module's eigenvector (r = -0.25; P = 3.3 x 10(-5)). We show that the effect of microbiota richness at 1 week on risk for AR at age 6 years was mediated in part by the epigenetic signature of this module. Conclusions: Our results suggest that upper airway microbial composition in infancy contributes to the development of AR during childhood, and this trajectory is mediated, at least in part, through altered DNA methylation patterns in upper airway mucosal cells.
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