Inflammatory bowel disease environmental risk factors versus genetics based on migration epidemiological studies.

Abstract

Inflammatory bowel disease (IBD) experienced a rapid rise in incidence and prevalence in developing countries that parallels rates of accelerated industrialization in these regions.1 Migrant studies can investigate the epidemiological factors driving this change. Migrants form a unique population for investigating the evolving pattern of IBD incidence and prevalence globally. Groups migrating from areas of low IBD incidence to high IBD incidence will experience a shorter time period between risk factor exposure and disease onset. This is relevant for those risk factors related to the lifestyle of westernized countries. Studying the offspring of migrants will also provide new cohort data on generational changes and their relationship with IBD development. Furthermore, such investigations might elucidate information on the critical period of genetic versus environmental influence on IBD pathogenesis.2 Existing migrant studies highlight higher IBD incidence in migrants, suggesting that migrants adopt similar if not higher risks of IBD as their native counterparts in developed countries. The incidence of IBD is higher in first- and second-generation migrants,3 and second-generation migrants have more extensive disease in both adults3 and children.4 Age at time of migration also appears to be important, as those raised from birth in the adoptive country or those who migrated during childhood have the greatest risk of developing IBD compared with non-migrants, as well as those migrating to certain regions such as the Middle East.5 Furthermore, even a period of time living in a more westernized environment and returning to the original milieu might influence IBD risk.6 Proxy measures of the hygiene hypothesis is also more pronounced in migrants. Childhood rural dwelling, farm animal access, bedroom sharing, pet ownership, and pet feeding were associated with decreased development of IBD in migrant Middle Easterners, while not significant for non-migrants in Australia.7 IBD environmental factors might act differentially in different populations. In those who are exposed to an undeveloped environment, hygiene increases IBD development. However, in those who have been in a developed environment for several generations, the hygiene-related risk factors are no longer applicable to disease pathogenesis.8 Thus, the migrant population might be more sensitive for detecting the relationship between IBD and lifestyle of affluent countries. Genetic risk factors also play an important role in IBD pathogenesis as demonstrated by genome wide associations studies. Migrant populations might have a role in studying IBD epigenetics, which has been previously investigated. Epigenetic changes may mediate interactions between genes and environmental factors and thus might explain some of the missing heritability.9 Smoking is an environmental modifier of epigenetic state and NOD2 activation, which can influence the expression of microRNA-29 and indirectly the Th17 pathway.10 Studying key deoxyribonucleic acid methylation site differences between migrant and non-migrant populations while adjusting for lifestyle and dietary factors might provide greater insight into IBD epigenetics. Limitations of migrant studies include possible different health-seeking behavior and health literacy in migrant groups, hence reducing IBD detection. However, this suggests positive findings are likely of importance. Ethnic factors such as diet might be difficult to differentiate from true environmental effects on disease. This might be overcome by recruiting controls with similar characteristics. Overall, migrant studies provide a good opportunity to further delve into the complexities of the environment versus genetics of IBD.