AhR/IL-22 pathway as new target for the treatment of post-infectious irritable bowel syndrome symptoms - AgroParisTech Access content directly
Journal Articles Gut microbes Year : 2022

AhR/IL-22 pathway as new target for the treatment of post-infectious irritable bowel syndrome symptoms

Valentine Daugey
  • Function : Author
Mathieu Méleine
  • Function : Author
Denis Ardid


Alterations in brain/gut/microbiota axis are linked to Irritable Bowel Syndrome (IBS) physiopathology. Upon gastrointestinal infection, chronic abdominal pain and anxio-depressive comorbidities may persist despite pathogen clearance leading to Post-Infectious IBS (PI-IBS). This study assesses the influence of tryptophan metabolism, and particularly the microbiota-induced AhR expression, on intestinal homeostasis disturbance following gastroenteritis resolution, and evaluates the efficacy of IL-22 cytokine vectorization on PI-IBS symptoms. The Citrobacter rodentium infection model in C57BL6/ J mice was used to mimic Enterobacteria gastroenteritis. Intestinal homeostasis was evaluated as lowgrade inflammation, permeability, mucosa-associated microbiota composition, and colonic sensitivity. Cognitive performances and emotional state of animals were assessed using several tests. Tryptophan metabolism was analyzed by targeted metabolomics. AhR activity was evaluated using a luciferase reporter assay method. One Lactococcus lactis strain carrying an eukaryotic expression plasmid for murine IL-22 (L. lactis IL−22) was used to induce IL-22 production in mouse colonic mucosa. C. rodentiuminfected mice exhibited persistent colonic hypersensitivity and cognitive impairments and anxiety-like behaviors after pathogen clearance. These post-infectious disorders were associated with low-grade inflammation, increased intestinal permeability, decrease of Lactobacillaceae abundance associated with the colonic layer, and increase of short-chain fatty acids (SCFAs). During post-infection period, the indole pathway and AhR activity were decreased due to a reduction of tryptophol production. Treatment with L. lactis IL−22 restored gut permeability and normalized colonic sensitivity, restored cognitive performances and decreased anxiety-like behaviors. Data from the video-tracking system suggested an upgrade of welfare for mice receiving the L.lactis IL−22 strain. Our findings revealed that AhR/IL-22 signaling pathway is altered in a preclinical PI-IBS model. IL-22 delivering alleviate PI-IBS symptoms as colonic hypersensitivity, cognitive impairments, and anxiety-like behaviors by acting on intestinal mucosa integrity. Thus, therapeutic strategies targeting this pathway could be developed to treat IBS patients suffering from chronic abdominal pain and associated well-being disorders.
Fichier principal
Vignette du fichier
2022_Meynier_Gut_Microbes.pdf (4.14 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

hal-03555153 , version 1 (03-03-2022)





Maëva Meynier, Elodie Baudu, Nathalie Rolhion, Manon Defaye, Marjolène Straube, et al.. AhR/IL-22 pathway as new target for the treatment of post-infectious irritable bowel syndrome symptoms. Gut microbes, 2022, 14 (1), pp.1-21. ⟨10.1080/19490976.2021.2022997⟩. ⟨hal-03555153⟩
8880 View
316 Download



Gmail Facebook X LinkedIn More