Decreasing antibiotic use, the gut microbiota, and asthma in
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Childhood asthma incidence is decreasing in some parts of the world. Antibiotic use in infancy has been associated with increased asthma risk. In the present study, researchers tested the hypothesis that decrease in asthma incidence are linked to reduced antibiotic prescribing and mediated by changes in the gut bacterial community.

This study comprised of population-based and prospective cohort analyses. At the population level, administrative data from British Columbia and Canada was used (population 4·7 million), on annual rates of antibiotic prescriptions and asthma diagnosis, to assess the association between antibiotic prescribing (at age less than 1 year) and asthma incidence (at age 1–4 years). At the individual level, 2644 children from the Canadian Healthy Infant Longitudinal Development (CHILD) prospective birth cohort were examined for the association of systemic antibiotic use (at age less than 1 year) with the diagnosis of asthma (at age 5 years). In the same cohort, a mechanistic investigation of 917 children was done with available 16S rRNA gene sequencing data from faecal samples, to assess how composition of the gut microbiota relates to antibiotic exposure and asthma incidence.

At the population level between 2000 and 2014,
--asthma incidence in children (aged 1–4 years) showed an absolute decrease of 7·1 new diagnoses per 1000 children, from 27·3 (26·8–28·3) per 1000 children to 20·2 (19·5–20·8) per 1000 children (a relative decrease of 26·0%).

Reduction in incidence over the study period was associated with decreasing antibiotic use in infancy, from 1253·8 prescriptions per 1000 infants to 489·1 per 1000 infant. Asthma incidence increased by 24% with each 10% increase in antibiotic prescribing . In the CHILD cohort, after excluding children who received antibiotics for respiratory symptoms, asthma diagnosis in childhood was associated with infant antibiotic use (adjusted odds ratio [aOR] 2·15), with a significant dose–response; 114 of 2182 children unexposed to antibiotics had asthma by age 5 years, compared with 23 of 284 exposed to one course, five of 49 exposed to two courses, and six of 34 exposed to three or more courses (aOR 1·44). Increasing ?-diversity of the gut microbiota, defined as an IQR increase (25th to 75th percentile) in the Chao1 index, at age 1 year was associated with a 32% reduced risk of asthma at age 5 years.

In a structural equation model, researchers found the gut microbiota at age 1 year, characterised by ?-diversity, ?-diversity, and amplicon sequence variants modified by antibiotic exposure, to be a significant mediator between outpatient antibiotic exposure in the first year of life and asthma diagnosis at age 5 years.

These findings suggest that the reduction in the incidence of paediatric asthma observed in recent years might be an unexpected benefit of prudent antibiotic use during infancy, acting via preservation of the gut microbial community.