Published online Jun 7, 2023. doi: 10.3748/wjg.v29.i21.3222
Peer-review started: December 28, 2022
First decision: January 10, 2023
Revised: January 23, 2023
Accepted: May 8, 2023
Article in press: May 8, 2023
Published online: June 7, 2023
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.
Core Tip: The ileum is most frequently affected by Crohn’s disease (CD). Ileal CD differs from other CD types in its epidemiology and natural history. Anatomical and histological features of the ileum provide the keys to understanding this distinct phenotype. Moreover, we discuss herein the crosstalk that occurs in the ileum between an individual and her/his environment and the clinical significance.