Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in both pediatric and adult populations. The development of AD has been linked to antibiotic usage, which causes perturbation of the microbiome and has been associated with abnormal immune system function. However, imbalances in the gut microbiome itself associated with antibiotic usage have been inconsistently linked to AD.
Objectives: This study aimed to elucidate the timing and specific factors mediating the relationship between systemic (oral or intravenous) antibiotic usage and AD.
Methods: We used statistical modeling and differential analysis to link CHILD Cohort Study participants' history of antibiotic usage and early-life gut microbiome alterations to AD.
Results: Here we report that systemic antibiotics during the first year of life, as compared to later, are associated with AD risk (adjusted odds ratio [aOR] = 1.81; 95% CI: 1.28-2.57; P < .001), with an increased number of antibiotic courses corresponding to a dose response-like increased risk of AD risk (1 course: aOR: 1.67; 95% CI: 1.17-2.38; 2 or more courses: aOR: 2.16; 95% CI: 1.30-3.59). Further, we demonstrate that microbiome alterations associated with both AD and systemic antibiotic usage fully mediate the effect of antibiotic usage on the development of AD (βindirect = 0.072; P < .001). Alterations in the 1-year infant gut microbiome of participants who would later develop AD included increased Tyzzerella nexilis, increased monosaccharide utilization, and parallel decreased Bifidobacterium and Eubacterium spp, and fermentative pathways.
Conclusions: These findings indicate that early-life antibiotic usage, especially in the first year of life, modulates key gut microbiome components that may be used as markers to predict and possibly prevent the development of AD.
Keywords: Atopic dermatitis; antibiotics; microbiome; pediatrics; structural equation modeling.
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