TY - JOUR

T1 - Epigenetic landscape links upper airway microbiota in infancy with allergic rhinitis at 6 years of age

AU - Morin, Andréanne

AU - McKennan, Chris G.

AU - Pedersen, Casper-Emil T.

AU - Stokholm, Jakob

AU - Chawes, Bo L.

AU - Schoos, Ann-Marie Malby

AU - Naughton, Katherine A.

AU - Thorsen, Jonathan

AU - Mortensen, Martin S.

AU - Vercelli, Donata

AU - Trivedi, Urvish

AU - Sørensen, Søren J.

AU - Bisgaard, Hans

AU - Nicolae, Dan L.

AU - Bønnelykke, Klaus

AU - Ober, Carole

PY - 2020

Y1 - 2020

N2 - 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 leaves 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 (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)2010 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=3.3x10-5). 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. Conclusion 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.

AB - 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 leaves 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 (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)2010 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=3.3x10-5). 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. Conclusion 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.

KW - Allergic rhinitis

KW - microbiota

KW - DNA methylation

KW - gene expression

KW - early life

KW - upper airways

U2 - 10.1016/j.jaci.2020.07.005

DO - 10.1016/j.jaci.2020.07.005

M3 - Journal article

C2 - 32693091

VL - 146

SP - 1358

EP - 1366

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 6

ER -