Inflammatory bowel diseases (IBDs), represented by Crohn disease and ulcerative colitis, are 
associated with major morbidity in Western countries and with increasing incidence in the developing 
world. Although analysis of the genome of patients with IBD, 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 finding has revealed that environmental 
factors also play a major 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 found to be dysregulated in this patient population. Therefore, IBD 
pathogenesis is a result of the interplay of genetic susceptibility and environmental impact on the 
microbiome that through a weakened intestinal barrier will lead to inappropriate intestinal immune 
activation. In this article, we will review the mechanisms proposed to cause IBD from the genetic, 
environmental, intestinal barrier, and immunologic perspectives.