Gene-by-environment interactions modulate the infant gut microbiota in asthma and atopy.
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BACKGROUND: Gut microbiota has been associated with health and susceptibility to childhood diseases, including asthma and allergies. However, the genomic factors contributing to inter-individual variations in gut microbiota remain poorly understood. OBJECTIVE: Our study integrates host genomics with early-life exposures to investigate main and interaction effects on gut microbiota during the first year of life. In addition, we identified gut microbes associated with childhood respiratory (asthma, wheeze) and atopic (atopic dermatitis, food/inhalant sensitization) outcomes. METHODS: We leveraged microbiome data from infant stool at ages 3 months (N=779) and 1 year (N=770) from the CHILD Cohort Study. We identified microbial taxa and co-occurring network clusters associated with asthma and atopy by age 5 years. Genome-wide association studies and gene-by-environment interaction analyses determined main and interaction effects of host genomics and early-life environmental exposures (e.g., feeding practices, household pets, birth characteristics) on gut microbial features. RESULTS: Shifts in microbial taxa and network clusters during the first year of life were associated with childhood respiratory and atopic outcomes (P<0.05), some of which were sex-specific. Additionally, some of these implicated microbes were associated with host genomics and early-life exposures. For example, Blautia obeum was associated with reduced food/inhalant sensitization and genetic variants near the MARCO gene (P=9.4E-11). Also, variants in the SMAD2 gene interact with breastfeeding to influence the green microbial network cluster (P=8.3E-10), associated with asthma. CONCLUSION: Our study reports main and interaction effects of genomics and exposures on early-life gut microbiota, which may contribute to childhood asthma and atopy. Improved understanding of the factors contributing to gut dysbiosis will inform on early-life biomarkers and interventions.
