Joyce WY Mak1, Yang Sun2, Amy L Wilson-O’Brien3, Xiaoqing Lin4, Mark Morrison5, Jessica YL Ching1, Junkun Niu2, Amy L Hamilton3, Rui Feng4, Whitney Tang1, Leo Or1, Gina L. Trakman3, Winnie Lin1, Ming Hu Chen4, Yinglei Mao2, Michael A Kamm3, Siew C Ng1

1Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China, 2Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, China, 3Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; Department of Medicine, The University of Melbourne, Melbourne, Australia, 4Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, 5The University of Queensland Diamantina Institute, Faculty of Medicine, Brisbane, Australia.

Background/Aims: We aimed to study early life environmental risk factors associated with development of Crohn’s Disease (CD) in populations at risk for CD in Chinese and Caucasian populations.

Methods: This is a case-control study in Australia and three cities in China (Hong Kong, Guangzhou and Kunming) which included four participant groups: patients with CD, at-risk individuals including non-affected first-degree relatives (FDR) and household members of CD patients, and unrelated healthy controls. Environmental risk factors including 14 categories were assessed using self-developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development.

Results: From 2017-2019, a total of 254 patients with CD (100 Australia, 154 China; mean age: 37.98±13.76 years; 58.3% male), 73 FDR (28 Australia, 45 China; mean age: 49.35±13.28 years; 46.6% male), 122 household members (50 Australia, 72 China; mean age: 45.50±13.25 years; 47.5% male) and 83 HC (25 Australia,58 China; mean age: 46.21±11.46; 48.2% male) were recruited. Significantly more CD patients were exposed to antibiotics before 18 years old compared to their FDR and household members (84.86% vs. 73.3%; p=0.011). Comparing CD patients (n=254) to their FDR (n=73) and household members (n=122), antibiotic use before 18 years old was risk factor for CD development (Adjusted OR 3.46, 95% CI 1.38-8.69; p=0.008). There was no significant difference in other childhood environmental risk factors including exposure to hot water tap, flush toilet and animals at home between CD and their FDR and household members.

Conclusion: Use of antibiotic before 18 years old was risk factor for CD development compared to their non-affected FDR and Household members. Environmental exposure may be if not as important as genetic susceptibility in CD development. Attention should be paid to identifying potential modifiable environmental risk factors in early childhood in at-risk family members in the future.

Keywords: Environmental risk factors, Inflammatory bowel disease , Crohn's disease