Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Translational Medicine Program, The Hospital for Sick Children, Toronto, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
J Allergy Clin Immunol. 2024 Jul;154(1):131-142. doi: 10.1016/j.jaci.2024.03.025. Epub 2024 Apr 24.
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.
This study aimed to elucidate the timing and specific factors mediating the relationship between systemic (oral or intravenous) antibiotic usage and AD.
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.
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 (β = 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.
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.
特应性皮炎(AD)是儿科和成人人群中最常见的慢性炎症性皮肤病。AD 的发展与抗生素的使用有关,这会导致微生物组的紊乱,并与免疫系统功能异常有关。然而,抗生素使用与肠道微生物组本身的失衡与 AD 之间的关联并不一致。
本研究旨在阐明全身(口服或静脉内)抗生素使用与 AD 之间关系的时间和具体介导因素。
我们使用统计建模和差异分析将 CHILD 队列研究参与者的抗生素使用史和生命早期肠道微生物组的改变与 AD 联系起来。
在这里,我们报告称,与生命后期相比,生命第一年的全身抗生素与 AD 风险相关(调整后的优势比[aOR] = 1.81;95%置信区间[CI]:1.28-2.57;P <.001),使用的抗生素疗程越多,AD 风险呈剂量反应样增加(1 个疗程:aOR:1.67;95% CI:1.17-2.38;2 个或更多疗程:aOR:2.16;95% CI:1.30-3.59)。此外,我们证明与 AD 和全身抗生素使用相关的微生物组改变完全介导了抗生素使用对 AD 发展的影响(β=0.072;P <.001)。AD 患者肠道微生物组在 1 岁时的改变包括 Tyzzerella nexilis 增加、单糖利用率增加、双歧杆菌和真杆菌属及发酵途径减少。
这些发现表明,生命早期的抗生素使用,尤其是在生命的第一年,会调节关键的肠道微生物组成分,这些成分可能被用作预测和可能预防 AD 发展的标志物。