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Abstracts of the 2019 Annual Conference of the International Society for Environmental Epidemiology, August 25-28 2019, Utrecht, the Netherlands

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

H, Sbihi1,,2; D, Patrick1,,3; D, Dai1,,2; A, Al Mamun3; P, Subbarao4,,5; T, Moraes4,,5; M, Azad6; P, Mandhane7; B, Finlay1,,8; S, Turvey1,,2

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doi: 10.1097/01.EE9.0000609884.44742.0c
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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.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Environmental Epidemiology. All rights reserved.