World J Gastroenterol. 2023 Jun 7;29(21):3222-3240.doi: 10.3748/wjg.v29.i21.3222.

Nicolas Richard ^1 2 3, Guillaume Savoye ^1 2 3, Mathilde Leboutte ^1 3, Asma Amamou ⁴, Subrata Ghosh ⁴, Rachel Marion-Letellier ^1 5

Author information

¹University of Rouen Normandie, INSERM, ADEN UMR 1073, Nutrition, Inflammation and Microbiota-Gut-Brain Axis, Rouen F-76000, France.

²CHU Rouen, Department of Gastroenterology, Rouen University Hospital-Charles Nicolle, Rouen F-76000, France.

³Institute for Research and Innovation in Biomedicine, University of Rouen Normandie, Rouen F-76000, France.

⁴APC Microbiome Ireland, Biosciences Building, University College Cork, Cork T12 YT20, Ireland.

⁵Institute for Research and Innovation in Biomedicine, University of Rouen Normandie, Rouen F-76000, France. rachel.letellier@univ-rouen.fr.

Abstract

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.