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

Autor: Meynier M; M2iSH, UMR 1071 INSERM, University of Clermont Auvergne, INRAE USC 2018, Clermont-Ferrand 63001, France.; NeuroDol, UMR 1107 INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France., Baudu E; M2iSH, UMR 1071 INSERM, University of Clermont Auvergne, INRAE USC 2018, Clermont-Ferrand 63001, France.; NeuroDol, UMR 1107 INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France., Rolhion N; Sorbonne University, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012 Paris, France.; Paris Centre for Microbiome Medicine FHU, Paris, France., Defaye M; NeuroDol, UMR 1107 INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France.; Department of Physiology and Pharmacology, Inflammation Research Network, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.; LMGE, CNRS 6023, University of Clermont Auvergne, Clermont-Ferrand 63001, France., Straube M; Sorbonne University, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012 Paris, France., Daugey V; NeuroDol, UMR 1107 INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France., Modoux M; Sorbonne University, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012 Paris, France., Wawrzyniak I; LMGE, CNRS 6023, University of Clermont Auvergne, Clermont-Ferrand 63001, France., Delbac F; LMGE, CNRS 6023, University of Clermont Auvergne, Clermont-Ferrand 63001, France., Villéger R; M2iSH, UMR 1071 INSERM, University of Clermont Auvergne, INRAE USC 2018, Clermont-Ferrand 63001, France., Méleine M; NeuroDol, UMR 1107 INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France., Borras Nogues E; Université Paris-Saclay, Institut National de la Recherche Agronomique et Environnementale (INRAE), AgroParisTech UMR 1319 MICALIS, Jouy-en-Josas, France., Godfraind C; M2iSH, UMR 1071 INSERM, University of Clermont Auvergne, INRAE USC 2018, Clermont-Ferrand 63001, France.; CHU Clermont-Ferrand, Neuropathology Unit, Clermont-Ferrand, France., Barnich N; M2iSH, UMR 1071 INSERM, University of Clermont Auvergne, INRAE USC 2018, Clermont-Ferrand 63001, France., Ardid D; NeuroDol, UMR 1107 INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France., Poirier P; M2iSH, UMR 1071 INSERM, University of Clermont Auvergne, INRAE USC 2018, Clermont-Ferrand 63001, France.; CHU Clermont-Ferrand, Laboratoire de Parasitologie et de Mycologie, Clermont-Ferrand, France., Sokol H; Sorbonne University, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012 Paris, France.; Paris Centre for Microbiome Medicine FHU, Paris, France.; Université Paris-Saclay, Institut National de la Recherche Agronomique et Environnementale (INRAE), AgroParisTech UMR 1319 MICALIS, Jouy-en-Josas, France., Chatel JM; Université Paris-Saclay, Institut National de la Recherche Agronomique et Environnementale (INRAE), AgroParisTech UMR 1319 MICALIS, Jouy-en-Josas, France., Langella P; Université Paris-Saclay, Institut National de la Recherche Agronomique et Environnementale (INRAE), AgroParisTech UMR 1319 MICALIS, Jouy-en-Josas, France., Livrelli V; M2iSH, UMR 1071 INSERM, University of Clermont Auvergne, INRAE USC 2018, Clermont-Ferrand 63001, France.; CHU Clermont-Ferrand, Laboratoire de Parasitologie et de Mycologie, Clermont-Ferrand, France., Bonnet M; M2iSH, UMR 1071 INSERM, University of Clermont Auvergne, INRAE USC 2018, Clermont-Ferrand 63001, France., Carvalho FA; NeuroDol, UMR 1107 INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France.
Jazyk: angličtina
Zdroj: Gut microbes [Gut Microbes] 2022 Jan-Dec; Vol. 14 (1), pp. 2022997.
DOI: 10.1080/19490976.2021.2022997
Abstrakt: 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 low-grade 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. rodentium -infected 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.
Databáze: MEDLINE
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