Early-life antibiotic exposure, the gut microbiome, and the risk of childhood asthma

Abstract

OPS 07: Farm animals, antibiotics, infections and the microbiome, Room 110, Floor 1, August 27, 2019, 10:30 AM - 12:00 PM Background: Many early-life features of Westernized lifestyle are risk factors for asthma. Several of these factors, in particular antibiotics, are modifiable, yet have not been addressed despite: (1) high asthma prevalence, (2) mounting evidence in support of exposure to beneficial microbes in infancy, and (3) documented decreased antibiotic prescriptions in British Columbia (BC), Canada, that parallels a decrease in pediatric asthma. Here, we harness the power of a three-tier study to explore causation and biological plausibility by defining the associations between early-life antibiotic use, the structure of the gut microbiome, and the risk of asthma. Methods: We used administrative linked health data to examine the association between antibiotic prescribing (age<1yr) and asthma incidence (ages 1-4yr) at the ecological level and examined 2,644 children from the Canadian Healthy Infant Longitudinal Development (CHILD) Study, who were clinically assessed for asthma (5yr). In an asthma-enriched subset (n=1,000), gut microbiota was defined by 16SrRNA sequencing of stool samples collected at 3 and 12 months of age Results: We report a 76% decrease in antibiotic use among children in BC and a decline in asthma incidence. Antibiotic prescribing predicted asthma incidence (IRR=1.2 for 10% increase; p<0.001). In the CHILD study, we also demonstrate a near doubling of asthma risk among participants who received systemic antibiotic use in the first year of life (aOR: 1.8, p=0.006), while this risk was reduced with increased gut microbiota α-diversity (aOR=0.68 for one IQR increase; p=0.046). The gut microbiota, represented by diversity and differentially expressed taxa, was a significant mediator between antibiotics and asthma (p=0.041). Conclusion: Antibiotic exposure in the first year of life increases the risk of being diagnosed with asthma in childhood. Our findings are consistent with a mechanism by which antibiotics disturb the balance of the microflora skewing the developing immune system toward hypersensitivity.