Decreasing antibiotic use, the gut microbiota, and asthma incidence in children: evidence from population-based and prospective cohort studies.
Level 3 - non-randomized controlled study
Non-randomized prospective birth cohort combined with population-level observational data
PubMed 32220282 · doi:10.1016/S2213-2600(20)30052-7
What was done
Researchers evaluated the relationship between infant antibiotic use, gut microbiota, and childhood asthma using two data sources: (1) population-level administrative data from British Columbia, Canada (2000–2014, ~4.7 million population) comparing annual antibiotic prescription rates in infants (<1 year) to asthma incidence in children aged 1–4 years; and (2) individual-level data from 2,644 children in the prospective Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort assessing systemic antibiotic exposure (<1 year, excluding prescriptions for respiratory symptoms) and asthma diagnosis at 5 years. In a subgroup of 917 CHILD participants, fecal 16S rRNA gene sequencing was performed at ≤1 year to assess gut microbiota composition and its mediation of asthma risk via structural equation modeling.
What was found
Between 2000 and 2014, BC asthma incidence in children aged 1–4 years decreased by 26.0% (from 27.3 [95% CI 26.8–28.3] to 20.2 [19.5–20.8] per 1,000 children), paralleling a drop in infant antibiotic prescriptions from 1,253.8 (95% CI 1,219.3–1,288.9) to 489.1 (467.6–511.2) per 1,000 infants (Spearman r = 0.81, p < 0.0001). Each 10% increase in population antibiotic prescribing was associated with a 24% increase in asthma incidence (adjusted incidence rate ratio 1.24 [95% CI 1.20–1.28], p < 0.0001). In the CHILD cohort, infant antibiotic use was associated with asthma at age 5 (adjusted odds ratio [aOR] 2.15 [95% CI 1.37–3.39], p = 0.0009), with a dose-response: 5.2% (114/2,182) unexposed, 8.1% (23/284) with 1 course, 10.2% (5/49) with 2 courses, and 17.6% (6/34) with ≥3 courses (aOR 1.44 [95% CI 1.16–1.79], p = 0.0008). Increased gut microbiota α-diversity (Chao1 index IQR increase) at age 1 year was associated with reduced asthma risk (aOR 0.68 [95% CI 0.46–0.99], p = 0.046). Structural equation modeling showed gut microbiota significantly mediated the relationship between infant antibiotic exposure and asthma at age 5 (β = 0.08, p = 0.027).
Why it matters
This study links population-level declines in pediatric asthma to reduced infant antibiotic prescribing and identifies preservation of gut bacterial diversity as a likely mediating pathway. The findings support conservative antibiotic stewardship in early infancy to protect long-term respiratory health.
Limits
The study is observational and cannot establish definitive causality. Population-level administrative data are vulnerable to ecological fallacy and lack clinical detail. Microbiome profiling was limited to a single stool sample collected at or before 1 year of age in a subset of the cohort (n = 917), and residual confounding from early infections or unmeasured environmental and dietary factors remains possible.
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