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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:146

Article

Morin, Andreanne¹  McKennan, Chris G.²  Pedersen, Casper-Emil T.³  Stokholm, Jakob³  Chawes, Bo L.³  Schoos, Ann-Marie Malby³  Naughton, Katherine A.¹  Thorsen, Jonathan³  Mortensen, Martin S.⁴  Vercelli, Donata^5,6  Trivedi, Urvish⁴  Sorensen, Soren J.⁴  Bisgaard, Hans³  Nicolae, Dan L.^1,2  Bonnelykke, Klaus³  Ober, Carole¹ 

[1] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[2] Univ Chicago, Dept Stat, Chicago, IL 60637 USA

[3] Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Copenhagen, Denmark

[4] Univ Copenhagen, Sect Microbiol, Dept Biol, Copenhagen, Denmark

[5] Univ Arizona Hlth Sci, Dept Cellular & Mol Med, Tucson, AZ USA

[6] Univ Arizona Hlth Sci, Asthma & Airway Dis Res Ctr, Tucson, AZ USA

关键词: Allergic rhinitis;    microbiota;    DNA methylation;    gene expression;    early life;    upper airways;   

DOI  :  10.1016/j.jaci.2020.07.005

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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