Antibiotic Treatments During Infancy, Changes in Nasal Microbiota, and Asthma Development: Population-based Cohort Study

BACKGROUND: Early-life exposures to antibiotics may increase the risk of developing childhood asthma. However, little is known about the mechanisms linking antibiotic exposures to asthma. We hypothesized that changes in the nasal airway microbiota serve as a causal mediator in the antibiotics–asthma link. METHODS: In a population-based birth-cohort study in Finland, we identified longitudinal nasal microbiota profiles during age 2–24 months using 16S rRNA gene sequencing and an unsupervised machine learning approach. We performed a causal mediation analysis to estimate the natural direct effect of systemic antibiotic treatments during age 0–11 months on risks of developing physician-diagnosed asthma by age 7 years and the natural indirect (causal mediation) effect through longitudinal changes in nasal microbiota. RESULTS: In our birth cohort of 697 children, 8.0% later developed asthma. Exposure to ≥2 antibiotic treatments during age 0–11 months was associated with a 4.0% increase in the absolute risk of developing asthma (absolute increase, 95% CI, .9–7.2%; P = .006). The unsupervised clustering approach identified 6 longitudinal nasal microbiota profiles. Infants with a larger number of antibiotic treatments had a higher risk of having a profile with early Moraxella sparsity (per each antibiotic treatment, adjusted RRR, 1.38; 95% CI, 1.15–1.66; P < .001). This effect of antibiotics on asthma was partly mediated by longitudinal changes in the nasal microbiota (natural indirect effect, P = .008), accounting for 16% of the total effect. CONCLUSIONS: Early exposures to antibiotics were associated with increased risk of asthma; the effect was mediated, in part, by longitudinal changes in the nasal airway microbiota.