Childhood antibiotics as a risk factor for Crohn's disease: The ENIGMA International Cohort Study

Joyce W Y Mak; Sun Yang; Annalise Stanley; Xiaoqing Lin; Mark Morrison; Jessica Y L Ching; Junkun Niu; Amy L Wilson-O'Brien; Rui Feng; Whitney Tang; Amy L Hamilton; Leo Or; Gina L Trakman; Winnie Y Y Lin; Joseph J Y Sung; Ming Hu Chen; Yinglei Mao; Michael A Kamm; Siew C Ng

doi:10.1002/jgh3.12755

Childhood antibiotics as a risk factor for Crohn's disease: The ENIGMA International Cohort Study

JGH Open. 2022 Jun 1;6(6):369-377. doi: 10.1002/jgh3.12755. eCollection 2022 Jun.

Authors

Joyce W Y Mak¹, Sun Yang², Annalise Stanley³, Xiaoqing Lin⁴, Mark Morrison⁵, Jessica Y L Ching¹, Junkun Niu², Amy L Wilson-O'Brien^{3

6}, Rui Feng⁴, Whitney Tang^{1

7

8}, Amy L Hamilton^{3

6}, Leo Or^{1

7}, Gina L Trakman^{3

6}, Winnie Y Y Lin^{1

8}, Joseph J Y Sung⁹, Ming Hu Chen⁴, Yinglei Mao², Michael A Kamm^{3

6}, Siew C Ng^{1

7

8}

Affiliations

¹ Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong Shatin Hong Kong.
² Department of Gastroenterology First Affiliated Hospital of Kunming Medical University Kunming Yunnan China.
³ Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.
⁴ The First Affiliated Hospital Sun Yat-sen University Guangzhou China.
⁵ Diamantina Institute, Faculty of Medicine The University of Queensland Brisbane Queensland Australia.
⁶ Present address: Department of Medicine The University of Melbourne Melbourne Victoria Australia.
⁷ LKS Institute of Health Sciences, State Key Laboratory of Digestive Disease The Chinese University of Hong Kong Shatin Hong Kong.
⁸ Microbiota I-Center (MagIC) Hong Kong.
⁹ Lee Kong Chian School of Medicine Nanyang Technological University Singapore.

Abstract

Background and aim: 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.

Methods: 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.

Results: 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; P = 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; P = 0.005) but not in Australian populations (OR 1.80, 95% CI 0.33-9.95; P = 0.498).

Conclusion: 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.

Keywords: Crohn's; antibiotics; environmental risk factors.