Epigenetic landscape links upper airway microbiota in infancy with allergic rhinitis at 6 years of age.
Allergic rhinitis
DNA methylation
early life
gene expression
microbiota
upper airways
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
06
05
2020
revised:
19
06
2020
accepted:
02
07
2020
pubmed:
22
7
2020
medline:
18
3
2021
entrez:
22
7
2020
Statut:
ppublish
Résumé
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). 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. 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. 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 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.
Sections du résumé
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
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.
Identifiants
pubmed: 32693091
pii: S0091-6749(20)30967-2
doi: 10.1016/j.jaci.2020.07.005
pmc: PMC7821422
mid: NIHMS1623223
pii:
doi:
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1358-1366Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL129735
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI133765
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI144722
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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