Epigenetic landscape links upper airway microbiota in infancy with allergic rhinitis at 6 years of age

Andréanne Morin, Chris G McKennan, Casper-Emil T Pedersen, Jakob Stokholm, Bo L Chawes, Ann-Marie Malby Schoos, Katherine A Naughton, Jonathan Thorsen, Martin S Mortensen, Donata Vercelli, Urvish Trivedi, Søren J Sørensen, Hans Bisgaard, Dan L Nicolae, Klaus Bønnelykke, Carole Ober*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


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 (ρ = -0.25; P = 3.3 × 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.

Sider (fra-til)1358-1366
Antal sider9
TidsskriftJournal of Allergy and Clinical Immunology
Udgave nummer6
StatusUdgivet - dec. 2020
Udgivet eksterntJa

Bibliografisk note

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.


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