Abstract
Background: Environmental, genetic, and microbial factors are independently associated with childhood asthma. Objective: We sought to determine the roles of environmental exposures and 17q12-21 locus genotype in the maturation of the early-life microbiome in childhood asthma. Methods: We analyzed fecal 16s rRNA sequencing at age 3 to 6 months and age 1 year to characterize microbial maturation of offspring of participants in the Vitamin D Antenatal Reduction Trial. We determined associations of microbial maturation and environmental exposures in the mediation of asthma risk at age 3 years. We examined 17q12-21 genotype and microbial maturation associations with asthma risk in Vitamin D Antenatal Reduction Trial and the replication cohort Copenhagen Prospective Studies on Childhood Asthma 2010. Results: Accelerated fecal microbial maturation at age 3 to 6 months and delayed maturation at age 1 year were associated with asthma (P < .001). Fecal Bacteroides was reduced at age 3 to 6 months in association with subsequent asthma (P = .006) and among subjects with lower microbial maturation at age 1 year (q = 0.009). Sixty-one percent of the association between breast-feeding and asthma was mediated by microbial maturation at age 3 to 6 months. Microbial maturation and 17q12-21 genotypes exhibited independent, additive effects on childhood asthma risk. Conclusions: The intestinal microbiome and its maturation mediates associations between environmental exposures including breast-feeding and asthma. The intestinal microbiome and 17q12-21 genotype appear to exert additive and independent effects on childhood asthma risk.
Original language | English |
---|---|
Journal | Journal of Allergy and Clinical Immunology |
Volume | 151 |
Issue number | 6 |
Pages (from-to) | 1494-1502 |
Number of pages | 8 |
ISSN | 0091-6749 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:© 2023 American Academy of Allergy, Asthma & Immunology
Keywords
- 17q12-21
- asthma
- Bacteroides
- breast-feeding
- Microbiome