Why does Crohn's disease usually occur in terminal ileum?

Crohn's disease can affect any part of the gastrointestinal tract, but terminal ileum is the most frequent localization. The reason why Crohn's disease is primarily located in the distal part of the ileum remains unexplained. In this article it has been attempted to provide a compelling explanation why Crohn's disease usually occurs in terminal ileum. Recent data indicate that some individuals are genetically predisposed to develop ileal Crohn's disease. Two genetic alterations, the polymorphism of Caspase Associated Recruitment Domain (CARD15) and Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACM6), favour the colonization of terminal ileum by entero adherent-invasive Escherichia coli (AIEC). The adhesion of these bacteria to epithelial intestinal cells depends on Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 expression in ileal epithelial cells and on the reduced ileal defensins expressed in a CARD15 dependent manner. Genetic defects in Authophagy-related 16-like gene (ATG16L1) and Immunity-related Guanosine Triphospatase (IRGM) recently found in ileal CD patients lead to a reduction of bacterial killing by macrophages and consequent continuous immunological upstimulation, cytokine secretion, chronic inflammation of the ileum and tissue injury. On the basis of all these data Crohn's disease of the ileum seems to be a subset of the disease mainly genetically determined.