Objective:The rapid emergence of IBD in newly industrialized regions supports the importance of environmental risk factors in disease etiology. The GIVES-21 consortium including106 hospitals from 19regions(15 Asia,3 Latin America,1 Africa)aims to determine environmental and dietary risk factors of IBD in both industrialized and developing regions.
Materials and Methods:Incident IBD subjects diagnosed between 2021-22 and controls living in predefined, well-described geographical areas matched with sex, age, and geographical region were recruited in a 1:1 ratio. All cases and controls completed 3 questionnaires at recruitment on:1)Environmental factor(14 questions);2)Current food additives intake(27 questions),a purpose-built and validated questionnaire developed by specialist dietitians in Hong Kong and Australia to measure intake of food additives in past year before IBD diagnosis, and 3)Dietary pattern screener(9 questions)assessing Mediterranean diet adherence as an indicator of healthy dietary choices 3 months prior to IBD symptoms onset. Regions with complete data entry before 31 Oct 2023 were included. Conditional logistic regression models adjusting for age, sex, and socioeconomic status of the countries based on gross national income(GNI) per capita were used to estimate adjusted ORs(aOR) and 95% CIs. Crohn's disease(CD)and ulcerative colitis(UC) were analyzed separately and for Asian patients only.
Results: Incident cases 649[224 CD; 425 UC; 369(56.9%)male;Median age 37 years(Interquartile range 28–49 years)] from 15 regions in Latin America (Argentina, Mexico, and Uruguay; n=47),Central and South Asia(India, Kazakhstan, Saudi Arabia, Nepal; n=152) and East Asia (Brunei, China, Hong Kong,Indonesia,Macau,Malaysia,Thailand,Taiwan,and Vietnam; n=450) and 649 matched controls were recruited. In multivariate model, antibiotic use <age10 years of age(aOR0.42; 0.23 – 0.77), daily physical activities(aOR0.30; 0.19 – 0.48) and high vegetables intake (aOR0.21;0.07 – 0.59) were protective against CD while feeling stressed(aOR2.39; 1.33 – 4.31)and exposure to household smoking at 10-18 years(aOR2.54;1.56 – 4.13) was associated with increased odds for CD. In UC, feeling stressed increased the odds(aOR3.85;1.73 – 8.52)while daily physical activity(aOR0.42;0.23 – 0.77) and high cereals intake(aOR 0.30;0.13 – 0.68) were associated with decreased odds. In Asia, having pets at 0-10 years(aOR0.38;0.16 – 0.91) and high legumes intake(aOR0.45;0.23-091) were additional protective factors against UC. Family history of IBD, Mediterranean diet adherence and food additive intake did not correlate with subsequent IBD development.
Conclusion: In a population-based study across 15 regions, early life hygiene, dietary, physical and stress factors known to impact on the gut microbiome are associated with IBD development in regions with emerging and accelerating incidence.

Figure 1. Environmental and Dietary Factors associated with IBD development.
Figure 2. Food Additive intake and adherence to Mediterranean diet and development of IBD