Crohn's disease: Why the ileum?

Crohn's disease (CD) is an inflammatory bowel disease characterized by immune-mediated flares affecting any region of the intestine alternating with remission periods. In CD, the ileum is frequently affected and about one third of patients presents with a pure ileal type. Moreover, the ileal type of CD presents epidemiological specificities like a younger age at onset and often a strong link with smoking and genetic susceptibility genes. Most of these genes are associated with Paneth cell dysfunction, a cell type found in the intestinal crypts of the ileum. Besides, a Western-type diet is associated in epidemiological studies with CD onset and increasing evidence shows that diet can modulate the composition of bile acids and gut microbiota, which in turn modulates the susceptibility of the ileum to inflammation. Thus, the interplay between environmental factors and the histological and anatomical features of the ileum is thought to explain the specific transcriptome profile observed in CD ileitis. Indeed, both immune response and cellular healing processes harbour differences between ileal and non-ileal CD. Taken together, these findings advocate for a dedicated therapeutic approach to managing ileal CD. Currently, interventional pharmacological studies have failed to clearly demonstrate distinct response profiles according to disease site. However, the high rate of stricturing disease in ileal CD requires the identification of new therapeutic targets to significantly change the natural history of this debilitating disease.

Automated summary

Crohn's disease is an immune-mediated inflammatory bowel disease with alternating flares and remission periods. The ileum is frequently affected in this disease, and the ileal type of Crohn's disease has specific epidemiological characteristics such as a younger age at onset, smoking, and genetic susceptibility. Environmental factors, such as diet, along with the histological and anatomical features of the ileum, play a role in the susceptibility to inflammation. Different immune responses and cellular healing processes are observed between ileal and non-ileal Crohn's disease, suggesting the need for a dedicated therapeutic approach for managing ileal CD.