Abstract
The pathogenesis of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) is complex, and our knowledge on the topic is constantly growing. The two disorders are distinct, yet overlap in their clinical manifestations and underlying causes. This review aims to provide a broad overview of the numerous pathogenetic factors that can lead to the development of IBD, focusing on novel findings and on the differences between UC and CD. Recent advances in genetics have identified new components in the pathogenesis, as an example, the importance of Th17 lymphocytes and the IL-17/IL-23 pathway have been highlighted in both diseases, apart from the previously known Th1-Th2 driven processes. Genetic background of increased permeability has been explored in UC, and the role of defective autophagy was recently described in CD. Genetic alterations can lead to an exaggerated immune response to the resident microbial flora. This microflora is altered in IBD patients, probably due to their reduced ability to stabilize its bacterial components and due to different environmental factors. An exhaustive exploration of environmental factors is particularly important, as they can be influential in many cases. The impact of smoking is the most established environmental factor, having deleterious effects in CD and protective in UC. Recent opinions on other factors, such as early appendectomy, diet, reduced vitamin D levels, the use of specific medications, breastfeeding, personal hygiene and psychological factors are also discussed. Epigenetics, a new field of research, links environmental factors to genetics. Understanding these factors is of great significance as changing lifestyles and improving life circumstances have started to increase the prevalence of IBD also in developing countries.
Highlights
Inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) are chronic, remittent gastrointestinal disorders with a multifactorial pathogenesis (Figure 1)
In our review we have summarized current knowledge of genetic and environmental factors participating in the development of IBD, with special focus on differences between UC and CD
These genetic discoveries create the basis for developing novel biological therapies or the expansion of existing therapies, which were originally developed for other diseases, to IBD [187]
Summary
Inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) are chronic, remittent gastrointestinal disorders with a multifactorial pathogenesis (Figure 1). The role of environmental factors is supported by the fact that IBD is more prevalent in countries with a westernized lifestyle compared to developing countries. Dietary risk factors of IBD were found higher among Eastern European patients, which may at least partly explain the rapid increase of the disease in this area in recent decades [4]. The increased occurrence of IBD among immigrants from developing countries to high incidence areas provides evidence that this difference between industrialized and developing countries is not explained purely by genetics [5]. The growing incidence of IBD highlights the importance of understanding the role of environmental factors, and the use of this knowledge in the prevention and treatment of the disease
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