Decreases in pediatric asthma linked to reduced antibiotics, changes in gut bacteria
The incidence of asthma in children declined 26% from 2000 to 2014 in British Columbia, Canada, and researchers have linked the decrease to reductions in early antibiotic exposure, mediated by changes in gut microbiota.
“At both the population-level and individual-level, this study shows a robust association between antibiotic exposure in the first year of life and an increased risk of asthma in early childhood,” David M. Patrick, PhD, professor and infectious disease specialist at the School of Population and Public Health and medical epidemiology lead for antimicrobial resistance at the British Columbia Center for Disease Control, and colleagues wrote in The Lancet Respiratory Medicine. “The gut microbiota was found to be a significant mediator between antibiotics and asthma and the six bacterial taxa that differed in their relative abundance between antibiotic-exposed, asthmatic children and nonexposed, nonasthmatic children have established links with immunomodulatory functions.”
The population-based study analyzed data from a population of 4.7 million people in British Columbia to evaluate annual rates of antibiotic prescriptions and asthma diagnoses and assess the association between antibiotic prescribing in patients aged 1 year or younger and asthma incidence in those patients aged 1 to 4 years.
At the individual level, the researchers evaluated 2,644 children from the Canadian Healthy Infant Longitudinal Development (CHILD) prospective birth cohort; of those, 917 children with available 16S rRNA gene sequencing data were investigated to assess how gut microbiota related to antibiotic exposure and asthma incidence.
At the population level, from 2000 to 2014, asthma incidence in these children decreased by 7.1 new diagnoses per 1,000 children (27.3 to 20.2). Reduction in asthma incidence was associated with decreased antibiotic use in infancy, from 1,253.8 prescriptions per 1,000 infants to 489.1 per 1,000 infants from 2000 to 2014 (P < .0001). Asthma incidence increased by 24% after each 10% antibiotic prescription increase (adjusted RR = 1.24; 95% CI, 1.2-1.28; P < .0001).
After excluding children who received antibiotics for respiratory symptoms in the CHILD cohort, childhood asthma diagnosis was associated with antibiotic use in infancy (aOR = 2.15; 95% CI, 1.37-3.39; P = .0009). Researchers observed a significant dose-response in this cohort, with 114 (5.2%) of 2,182 children unexposed to antibiotics with asthma by age 5 years compared with 23 (8.1%) of 284 children exposed to one course, five (10.2%) of 49 exposed to two courses and six (17.6%) of 34 children exposed to three of more courses (aOR = 1.44; 95% CI, 1.16-1.79; P = .0008).
A 32% reduced risk for asthma at age 5 years was associated with increasing diversity of gut microbiota at age 1 year (aOR = 0.68; 95% CI, 0.46-0.99; P = .046). Researchers found significant mediators between outpatient antibiotic exposure in the first year of life and asthma diagnosis at age 5 years were gut microbiota at age 1 year and amplicon sequence variants modified by antibiotic exposure (P = .027).
“This work opens up the question of whether novel therapies should be used to maintain microbiota diversity following antibiotic exposure,” the researchers wrote. “However, we conclude that the shortest path to reducing asthma-related morbidity is by avoiding dysbiosis induced by unnecessary antibiotic therapy. Furthermore, the substantial reduction in pediatric asthma incidence observed in recent years is an unexpected yet plausible benefit of prudent antibiotic stewardship.”