Antibiotics within first year are linked to infant gut microbiome disruption and elevated atopic dermatitis risk

Courtney Hoskinson; Maria V Medeleanu; Myrtha E Reyna; Darlene Ly Dai; Biswajit Chowdhury; Theo J Moraes; Piushkumar J Mandhane; Elinor Simons; Anita L Kozyrskyj; Meghan B Azad; Charisse Petersen; Stuart E Turvey; Padmaja Subbarao

doi:10.1016/j.jaci.2024.03.025

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. Online ahead of print.

Authors

Affiliations

¹ Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
² Translational Medicine Program, The Hospital for Sick Children, Toronto, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Canada.
³ Translational Medicine Program, The Hospital for Sick Children, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
⁴ Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
⁵ Translational Medicine Program, The Hospital for Sick Children, Toronto, Canada.
⁶ Department of Pediatrics, University of Alberta, Edmonton, Canada.
⁷ Section of Allergy and Immunology, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
⁸ Section of Allergy and Immunology, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada; Department of Pediatrics, University of Alberta, Edmonton, Canada; Manitoba Interdisciplinary Lactation Centre (MILC), Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
⁹ Translational Medicine Program, The Hospital for Sick Children, Toronto, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. Electronic address: padmaja.subbarao@sickkids.ca.

PMID: 38670232
DOI: 10.1016/j.jaci.2024.03.025

Abstract

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.

Objective: 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 modelling and differential analysis to link CHILD participants' history of antibiotic usage and early-life gut microbiome alterations to atopic dermatitis.

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 < 0.001), 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 (β_indirect = 0.072, p < 0.001). 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, Eubacterium spp., and fermentative pathways.

Conclusion: Our 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.