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 leaves 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 (DNAm) and gene expression profiles in upper airway mucosal cells and assessed AR at age 6 in children in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohort RESULTS: We identified 956 AR-associated differentially methylated CpGs (DMCs) in upper airway mucosal cells at age 6; 792 of which formed three modules of correlated DMCs. The eigenvector of one 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=0.0079) in children with AR at age 6, and reduced diversity at 1 week was also correlated with the same module’s eigenvector (rho=-0.25, p=3.3×10). We show that the effect of microbiota richness at 1 week on risk for AR at age 6 was mediated in part by the epigenetic signature of this module.
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 DNAm patterns in upper airway mucosal cells.
Copyright © 2020. Published by Elsevier Inc.