Antibiotics in First Year Given to Infants Linked to Increased Eczema Risk, Microbiome Disruption

Early-life usage of systemic antibiotics, especially during the first year of an infant’s life, impacts key gut microbiome components and is associated with a dose-dependent risk increase for atopic dermatitis (AD), according to new findings.¹

Such findings are the conclusion of a recent study which was conducted with the goal of elucidating the timing and factors which impact systemic (oral or intravenous) antibiotic usage and eczema’s relationship. This research was led by Courtney Hoskinson, BS, of BC Children’s Hospital’s department of pediatrics at the University of British Columbia, Vancouver.

Hoskinson and colleagues noted that despite the existence of research on overuse of antibiotics and increased atopic dermatitis risk, there are few studies on the functional changes occurring within infants’ microbiomes connected with antibiotic usage.²

“Within this study, we leveraged the large-scale, longitudinal CHILD birth cohort to investigate the mediating role of early-life exposure to systemic antibiotics in the previously established relationship between (lower respiratory tract infections) and subsequent AD development,” Hoskinson and colleagues wrote. “We further interrogated the metagenomic microbiome profiles of nearly 1,450 infants using stool collected at 1 year to mechanistically link antibiotic disruption and elevated AD risk.”

Background and Methods

The investigators conducted the CHILD Study as a longitudinal, prospective birth cohort trial which lasted from 2008 - 2012. The research team enrolled 3621 pregnant women from 4 specified Canadian cities and included their infants (n=3455).

The infants looked at in the study had no congenital abnormalities. Participants involved in the CHILD study were monitored by the research team longitudinally, and detailed data was collected on environmental exposures as well as clinical outcomes through the use of questionnaires and in-person evaluations.

The team gave these questionnaires on environmental exposures and general health to the subjects at several different points from prenatal stages through to age 5, adding additional evaluations at ages 1, 3, and 5 years. The investigators considered several different covariates, including study center, birth weight Z-score adjusted for gestational age, the sex of the child, mode of delivery, season of child’s birth, breastfeeding status, presence of siblings, tobacco smoke exposure, and ethnicity.

The research team identified the child’s ethnic background through parental self-reports. The connection between subjects’ usage history of antibiotics, early-life changes in gut microbiome, and atopic dermatitis (AD) at age 5 was evaluated through use of differential analyses and statistical modeling.

The team looked at respiratory infections via the use of parent-completed questionnaires at different follow-up visits, with lower respiratory tract infections (LRTIs) being defined by specific symptoms. Overall, the team evaluated systemic antibiotics’ role in the relationship between early-life LRTIs and subjects’ development of clinical eczema at age 5, with a Generalized Linear Model (GLM) being used to calculate propensity scores.

Findings

The investigators reported that the use of systemic antibiotics within the initial year of life, as opposed to later years, was found to be associated with greater risk of atopic dermatitis development. This was indicated by an adjusted odds ratio (aOR) of 1.81 [95% CI = 1.28 - 2.57], P < .001.

Eczema risk was shown to rise depending on the number of antibiotic courses, indicating dose-dependent results. The research team also noted that shifts in participants’ microbiomes, which are related to systemic antibiotic implementation and eczema, explain the effect of antibiotic use on development of the skin condition (β_indirect = 0.072, P < .001).

The shifts the investigators noted in the gut microbiome of the infants at 1 year old who later developed eczema, included greater levels of Tyzzerella nexilis and enhanced monosaccharide utilization. They also included decreased levels of Eubacterium spp., Bifidobacterium, and fermentative pathways.

“This study provides insight into the microbial underpinnings driving the link between early-life respiratory infections, antibiotic usage and the later development of AD,” they wrote. “This work reinforces the necessity of responsible antibiotic usage in pediatric populations and provides potential targets for the prediction and prevention of AD.”

References

1. ^{Hoskinson C, Medeleanu MV, Subbarao P, et al. Antibiotics within first year are linked to infant gut microbiome disruption and elevated atopic dermatitis risk. J Allergy Clin Immunol. 2024 Apr 24:S0091-6749(24)00409-3. doi: 10.1016/j.jaci.2024.03.025. Epub ahead of print. PMID: 38670232.}
2. ^{Adlerberth I, Strachan DP, Matricardi PM, Ahrné S, Orfei L, Aberg N, et al. Gut microbiota and development of atopic eczema in 3 European birth cohorts. J Allergy Clin Immunol. 2007;120(2):343-50.}