Mak Joyce W Y, Yang Sun, Stanley Annalise, Lin Xiaoqing, Morrison Mark, Ching Jessica Y L, Niu Junkun, Wilson-O'Brien Amy L, Feng Rui, Tang Whitney, Hamilton Amy L, Or Leo, Trakman Gina L, Lin Winnie Y Y, Sung Joseph J Y, Chen Ming Hu, Mao Yinglei, Kamm Michael A, Ng Siew C
Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong Shatin Hong Kong.
Department of Gastroenterology First Affiliated Hospital of Kunming Medical University Kunming Yunnan China.
JGH Open. 2022 Jun 1;6(6):369-377. doi: 10.1002/jgh3.12755. eCollection 2022 Jun.
Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations.
This case-control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at-risk individuals including non-affected first-degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs). Environmental risk factors, including childhood antibiotic use and 13 other categories, were assessed using a self-developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development.
From 2017 to 2019, a total of 254 patients with CD (mean age: 37.98 ± 13.76 years; 58.3% male), 73 FDR (mean age: 49.35 ± 13.28 years; 46.6% male), 122 HMs (including FDR) (mean age: 45.50 ± 13.25 years; 47.5% male), and 78 HC (mean age: 45.57 ± 11.24; 47.4% male) were included. Comparing CD patients with their FDR and HMs, antibiotic use before 18 years old was a risk factor for CD development (adjusted odds ratio [OR] 3.46, 95% confidence interval [CI] 1.38-8.69; = 0.008). There were no significant differences in other childhood environmental risk factors between CD and their FDR or HMs. Subgroup analysis showed that antibiotic use <18 years old was a risk factor for CD development in the Chinese (adjusted OR 4.80, 95% CI 1.62-12.24; = 0.005) but not in Australian populations (OR 1.80, 95% CI 0.33-9.95; = 0.498).
Use of antibiotics <18 years was a risk factor for CD development. Attention should be paid to identifying modifiable environmental risk factors in early childhood, especially in at-risk families.
环境因素在克罗恩病（CD）的发生发展中起关键作用，一般认为是通过肠道微生物群的变化介导的。我们旨在明确在不同地理区域人群中，抗生素暴露对CD后续发病的潜在影响。
这项在澳大利亚以及中国三个城市（香港、广州和昆明）开展的病例对照研究包括四组：CD患者、高危个体，包括未患病的一级亲属（FDR）和CD患者的家庭成员（HM），以及无关健康对照（HC）。使用自行编制的问卷评估环境危险因素，包括儿童期抗生素使用情况以及其他13类因素。采用逻辑回归和条件逻辑回归确定与CD发病相关的环境因素。
2017年至2019年，共纳入254例CD患者（平均年龄：37.98±13.76岁；男性占58.3%）、73名FDR（平均年龄：49.35±13.28岁；男性占46.6%）、122名HM（包括FDR）（平均年龄：45.50±13.25岁；男性占47.5%）和78名HC（平均年龄：45.57±11.24岁；男性占47.4%）。将CD患者与其FDR和HM进行比较，18岁之前使用抗生素是CD发病的危险因素（调整比值比[OR] 3.46，95%置信区间[CI] 1.38 - 8.69；P = 0.008）。CD患者与其FDR或HM在其他儿童期环境危险因素方面无显著差异。亚组分析显示，18岁之前使用抗生素是中国人群中CD发病的危险因素（调整OR 4.80，95% CI 1.62 - 12.24；P = 0.005），但在澳大利亚人群中并非如此（OR 1.80，95% CI 0.33 - 9.95；P = 0.498）。
18岁之前使用抗生素是CD发病的危险因素。应重视识别儿童早期尤其是高危家庭中可改变的环境危险因素。
