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World J Gastroenterol. Jun 7, 2023; 29(21): 3222-3240
Published online Jun 7, 2023. doi: 10.3748/wjg.v29.i21.3222
Crohn’s disease: Why the ileum?
Nicolas Richard, Guillaume Savoye, Mathilde Leboutte, Asma Amamou, Subrata Ghosh, Rachel Marion-Letellier
Nicolas Richard, Guillaume Savoye, Mathilde Leboutte, Rachel Marion-Letellier, University of Rouen Normandie, INSERM, ADEN UMR 1073, Nutrition, Inflammation and Microbiota-Gut-Brain Axis, Rouen F-76000, France
Nicolas Richard, Guillaume Savoye, CHU Rouen, Department of Gastroenterology, Rouen University Hospital-Charles Nicolle, Rouen F-76000, France
Nicolas Richard, Guillaume Savoye, Mathilde Leboutte, Rachel Marion-Letellier, Institute for Research and Innovation in Biomedicine, University of Rouen Normandie, Rouen F-76000, France
Asma Amamou, Subrata Ghosh, APC Microbiome Ireland, Biosciences Building, University College Cork, Cork T12 YT20, Ireland
Author contributions: Richard N wrote the first draft; all authors have read and approve the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Rachel Marion-Letellier, PhD, Associate Professor, University of Rouen Normandie, INSERM, ADEN UMR 1073, Nutrition, Inflammation and Microbiota-Gut-Brain Axis, 22 Boulevard Gambetta, Rouen F-76000, France.
Received: December 28, 2022
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.

Keywords: Ileum, Crohn’s disease, Bile acids, Paneth cells, Diet, Genetics, Strictures

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.