Abstract
Inflammatory Bowel Diseases (IBD), represented by Crohn’s Disease (CD) and Ulcerative
Colitis (UC), are associated with significant morbidity in western countries and with
increasing incidence in the developing world. While analysis of the genome of IBD
patients, especially through genome-wide association studies, has unraveled multiple
pathways involved in IBD pathogenesis only part of IBD heritability has been explained
by genetic studies. This has demonstrated that environmental factors also play a
significant role in promoting intestinal inflammation, mostly through their effects in
the composition of the microbiome. However, in order for microbial dysbiosis to result
in uncontrolled intestinal inflammation, the intestinal barrier formed by intestinal
epithelial cells and the innate immune system should also be compromised. Finally,
activation of the immune system depends on the working balance between effector and
regulatory cells present in the intestinal mucosa, which have also been shown to be
dysregulated in this patient population. Therefore, IBD pathogenesis is a result of the
interplay of genetic susceptibility, environmental impact on the microbiome that through
a weakened intestinal barrier will lead to inappropriate intestinal immune activation.
In this review, we will approach the mechanisms proposed to cause IBD from the genetic,
environmental, intestinal barrier and the immunologic perspectives.