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16 results on '"maladie inflammatoire intestinale"'

1. Développement de maladies inflammatoires intestinales au cours de traitement anti-TNF-α dans les rhumatismes inflammatoires. Étude nationale

Author

Toussirot, Éric, Houvenagel, Éric, Goëb, Vincent, Fouache, Damien, Martin, Antoine, Le Dantec, Philippe, Dernis, Emmanuelle, Wendling, Daniel, Ansemant, Thiphaine, Berthelot, Jean-Marie, Bader-Meunier, Brigitte, and Kantelip, Bernadette

Subjects
*INFLAMMATORY bowel diseases, *TUMOR necrosis factors, *JOINT diseases, *SYMPTOMS, *ANKYLOSING spondylitis, *INFLIXIMAB
Abstract

Résumé: Objectifs: Décrire les cas de patients développant une maladie inflammatoire intestinale (MICI) dans un contexte de rhumatisme inflammatoire (RI) traité par agents anti-TNF-α. Méthodes: Un appel à participation a été envoyé aux membres du club « rhumatismes et inflammation » français. Seuls les patients ne présentant pas de symptômes intestinaux avant l’introduction des agents anti-TNF-α étaient inclus. Résultats: En deux ans, 16 patients ont été inclus : neuf hommes et sept femmes, d’âge moyen 41,5 (±17,4) ans. Douze patients étaient atteints de spondylarthrite ankylosante (SA), un patient de polyarthrite rhumatoïde (PR), un patient de rhumatisme psoriasique et deux patients d’arthrite juvénile idiopathique (AJI) avec enthésites liées à l’atteinte articulaire. Globalement 14 patients étaient traités par étanercept et deux par infliximab. Le délai moyen entre le début du traitement par agents anti-TNF-α et le développement de la MICI était de 29,3±20,1 mois. Des analyses endoscopiques et histologiques ont permis de classer la MICI comme maladie de Crohn (MC) typique dans huit cas, une maladie de type Crohn dans six cas, une atteinte indéterminée dans un cas et une rectocolite ulcéreuse dans un dernier cas. Pour tous les patients, chaque traitement par agent anti-TNF-α a été interrompu et remplacé par un anticorps monoclonal anti-TNF-α (différent du premier le cas échéant). Après un suivi moyen de 23,4 (±19,5) mois, le traitement a été bénéfique sans récidive ni recrudescence de la MICI. Conclusions: Une MICI peut survenir de façon paradoxale au cours du traitement des RI par agents anti-TNF-α, principalement chez les patients ayant une spondylarthropathie traitée par étanerceptLa fréquence est estimée à 0,15 % chez les patients français atteints de spondylarthropathies et traités par des agents anti-TNF-α. La MICI correspond principalement à une MC ou de type Crohn. En revanche, l’apparition de nouvelles MICI est moins fréquente dans les autres types de RI chez les patients traités par d’autres agents anti-TNF-α. [Copyright &y& Elsevier]

Published
2012
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2. Toxicité des médicaments anti-inflammatoires non stéroïdiens sur l’intestin grêle, le côlon et le rectum

Author

Thiéfin, Gérard and Beaugerie, Laurent

Subjects
*TOXICITY testing, *NONSTEROIDAL anti-inflammatory agents, *COLON diseases, *GASTRIC diseases, *DUODENAL diseases, *INFLAMMATION, *ANEMIA, *CYCLOOXYGENASE 2, *INFLAMMATORY bowel diseases
Abstract

Abstract: The gastrointestinal toxicity of conventional non-steroidal anti-inflammatory drugs (NSAIDs) is not confined to the stomach and proximal duodenum but extends also to the rest of the small bowel, the colon, and the rectum. Long-term NSAID therapy usually induces clinically silent enteropathy characterized by inflammation and increased permeability of the gut wall. Chronic minimal bleeding and protein loss may result in iron-deficiency anemia and hypoalbuminemia. NSAIDs can also induce small bowel ulcers that infrequently lead to acute bleeding, perforation, or chronic scarring responsible for diaphragm-like strictures. At the colon and rectum, NSAID use can result in de novo lesions such as non-specific colitis and rectitis, ulcers, and diaphragm-like strictures. NSAIDs have been implicated in the development of segmental ischemic colitis. In patients with diverticular disease, NSAID use increases the risk of severe diverticular infection and perforation. NSAIDs can trigger exacerbations of ulcerative colitis or Crohn’s disease. With selective COX-2 inhibitors, the risk of gastrointestinal toxicity is reduced as compared to conventional NSAIDs but is not completely eliminated. Experimental studies suggest that long-term COX-2 inhibitor therapy may cause damage to the previously healthy small bowel. Similar to conventional NSAIDs, COX-2 inhibitors may be capable of triggering exacerbations of inflammatory bowel disease. [Copyright &y& Elsevier]

Published
2005
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3. Performances diagnostiques de la CRP, de l'albuminémie, de l'endoscopie et du scanner dans l'évaluation des ulcérations creusantes au cours de la rectocolite hémorragique

Author

Le Chevillier, Anne and UB, Médecine

Subjects
[SDV] Life Sciences [q-bio], Colectomie, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Endoscopie, Albumine, Maladie inflammatoire intestinale, CRP, Anatomie pathologique, Rectocolite hémorragique
Abstract

Introduction: deep ulcerations (DU) in ulcerative colitis (UC) is a commonly used severity criterion. The aim of this study was to evaluate the diagnostic performances of C-reactive protein (CRP), albuminemia, endoscopy and computed tomography (CT) to identify DU. Methods: in this retrospective study we included consecutively every patient who had a colectomy due to UC in Bordeaux University Hospital Center between January 2012 and February 2019. All operative specimens were studied by two different pathologists. Thus, patients were classified in two different groups: DU+ when they had histological colonic DU or rectal DU during a colonoscopy; DU- when they had no DU. We used electronic medical records to assess patients clinical, biochemical, endoscopic and CT data. Results: forty-nine patients who had colectomy were included: 41 had acute severe ulcerative colitis, 6 had treatment-refractory disease and 2 had dysplasia or colorectal cancer. There were 28 patients in DU+ group and 21 patients in DU- group. CRP was significantly higher when patients had DU (98.9 [IQR: 42.4; 155.3] mg/l) than when they did not (17.5 [IQR: 5.2; 53.5] mg/l) (p, Introduction : les ulcérations creusantes (UC) colorectales au cours de la colite aiguë grave (CAG) de rectocolite hémorragique (RCH) sont un critère de gravité. L’objectif était d’évaluer les performances de la C-réactive protéine (CRP), de l’albuminémie, de l’endoscopie et du scanner pour identifier les UC. Patients et Méthodes : dans cette étude rétrospective, les patients opérés pour RCH au CHU de Bordeaux entre Janvier 2012 et Février 2019 étaient inclus consécutivement. Les pièces de colectomie étaient relues en aveugle par deux médecins pathologistes. Les patients étaient classés en deux groupes : UC+ en cas d’UC colique en histologie ou d’UC rectale en endoscopie ; UC- en l’absence d’UC. Les données analysées étaient recueillies rétrospectivement à partir des dossiers informatisés. Résultats : parmi les 49 patients analysables, 41 ont été colectomisés pour CAG, 6 pour maladie réfractaire et 2 pour dysplasie ou cancer. Vingt-huit malades étaient classés UC+ et 21 UC-. La CRP était plus élevée dans le groupe UC+ (98.9 [IQR : 42.4 ; 155.3] mg/l) que dans le groupe UC- (17.5 [IQR : 5.2 ; 53.5] mg/l) (p

Published
2019

4. Chimioprévention du cancer colorectal dans les maladies inflammatoires intestinales chroniques. Quels sont les médicaments proposés ?

Author

Riis, Lene, Vind, Ida, Winther, Karen, Jess, Tine, and Munkholm, Pia

Abstract

Les maladies inflammatoires intestinales sont associées à une augmentation du risque de développer un cancer colorectal (CCR). La durée et l’étendue de la maladie sont des facteurs de risque importants, de même que la présence d’une cholangite sclérosante primitive (CSP) et un diagnostic à une âge précoce. La chimioprévention du cancer vise à empêcher, arrêter ou renverser la phase d’initiation ou de progression des cellules néoplasiques vers le cancer. Un intérêt croissant a été accordé aux agents chimiopréventifs potentiels dans la CCR sporadique et associée à la colite. Plusieurs études ont montré qu’une prise régulière de 5-aminosalicylates peut apporter une certaine protection contre le développement de la CCR dans les MICI. Chez les patients porteurs de colite ulcéreuse ou de CSP, il a été démontré que l’acide ursodéoxycolique pouvait réduire le risque de CCR. L’acide folique ne semble pas protecteur contre le cancer. Cet article donne un résumé d’un grand nombre d’études de diverses provenances, épidémiologiques, in vivo et in vitro, qui ont étudié la question de la chémoprévention dans les MICI. Inflammatory bowel disease (IBD) is associated with an increased risk of developing colorectal cancer (CRC). Both duration and extent of disease are important risk factors, as is the presence of primary sclerosing cholangitis (PSC) and early age at diagnosis. Chemoprevention of cancer aims to prevent, arrest or reverse the initiation phase or the progression of neoplastic cells to cancer. A growing interest in possible chemopreventive agents, in both sporadic and colitisassociated CRC has occurred. Several studies have indicated that regular intake of 5-aminosalicylates can provide some protection against the development of CRC in IBD. In patients with ulcerative colitis and PSC ursodeoxycolic acid has been shown to reduce the risk of CRC. Folic acid has not been proven cancer protective in IBD. The current review gives an overview of the evidence of a variety of sources including epidemiological, in vivo, and in vitro studies that have addressed the question of chemoprevention in IBD. [ABSTRACT FROM AUTHOR]

Published
2004
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5. Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease

Author

Alexandre Denadai-Souza, Chrystelle Bonnart, Núria Solà Tapias, Marlène Marcellin, Brendan Gilmore, Laurent Alric, Delphine Bonnet, Odile Burlet-Schiltz, Morley D. Hollenberg, Nathalie Vergnolle, Céline Deraison, Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Queen's University [Belfast] (QUB), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Chercheur indépendant, Centre de Physiopathologie Toulouse Purpan (CPTP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Project: 310973,EC:FP7:ERC,ERC-2012-StG_20111109,PIPE(2013), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), School of Pharmacy, Queen's University Belfast, Belfast, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), MARine Biodiversity Exploitation and Conservation (UMR MARBEC), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut de Recherche pour le Développement (IRD), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Schiltz, Odile, Physiology of the Intestine: Proteases from the Epithelium - PIPE - - EC:FP7:ERC2013-04-01 - 2018-03-31 - 310973 - VALID, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées

Subjects
Proteomics, Cathepsin G, lcsh:Medicine, approche protéomique, Article, PROBES, serine, SDG 3 - Good Health and Well-being, Tandem Mass Spectrometry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], BINDING, Humans, PROTEINASE-ACTIVATED RECEPTOR-2, Intestinal Mucosa, lcsh:Science, General, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Science & Technology, Gene Expression Profiling, lcsh:R, Thrombin, CATHEPSIN-G, protéase, pathophysiologie, Proteases, Inflammatory Bowel Diseases, maladie inflammatoire intestinale, digestive system diseases, Up-Regulation, Multidisciplinary Sciences, Hépatologie et Gastroentérologie, Mechanisms of disease, Gene Expression Regulation, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Science & Technology - Other Topics, Hépatology and Gastroenterology, lcsh:Q, Serine Proteases, INHIBITORS, ENZYMES, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, COLITIS, Chromatography, Liquid
Abstract

While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients. Profiling of (Pro-Lys)-ABP bound proteases revealed that most of hyperactive proteases from IBD secretome are clustered at 28-kDa. We identified seven active proteases: the serine proteases cathepsin G, plasma kallikrein, plasmin, tryptase, chymotrypsin-like elastase 3 A, and thrombin and the aminopeptidase B. Only cathepsin G and thrombin were overactive in supernatants from IBD patient tissues compared to healthy controls. Gene expression analysis highlighted the transcription of genes encoding these proteases into intestinal mucosae. The functional ABP-targeted proteomic approach that we have used to identify active proteases in human colonic samples bears directly on the understanding of the role these enzymes may play in the pathophysiology of IBD. ispartof: SCIENTIFIC REPORTS vol:8 issue:1 ispartof: location:England status: published

Published
2017
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6. Le système immunitaire muqueux dans les maladies inflammatoires intestinales.

Author

Brandtzaeg, P., Halstensen, T., and Kett, K.

Abstract

Copyright of Acta Endoscopica is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
1991
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7. Protectin D1n-3 DPA and resolvin D5n-3 DPA are effectors of intestinal protection

Author

Nathalie Vergnolle, Charles N. Serhan, Delphine Bonnet, Trond Vidar Hansen, Thomas Gobbetti, Céline Deraison, Marius Aursnes, Jesmond Dalli, Laurent Alric, Romain A. Colas, Mauro Perretti, Donata Federici Canova, William Harvey Research Institute, Barts and the London Medical School, Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital [Boston], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), University of Oslo (UiO), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), MCTRinIA (Project ID: 677542 H2020), William Harvey Research Foundation, National Institutes of Health Grant P01GM095467, Grant ERC-2012-STG_20111109, CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London (QMUL), Department of Pharmaceutical Chemistry, School of Pharmacy, Department of Internal Medicine and Digestive Diseases, Pole Digestif, Centre Hospitalier Universitaire de Toulouse, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)

Subjects
0301 basic medicine, Neutrophils, [SDV]Life Sciences [q-bio], propriété pharmacologique, Inflammation, Pharmacology, 03 medical and health sciences, chemistry.chemical_compound, Intravital microscopy, medicine, Omega-3 fatty acids, inflammation intestinale, Inflammation resolution, Colitis, Cell adhesion, application thérapeutique, chemistry.chemical_classification, Multidisciplinary, Specialized proresolving mediators, Chemistry, Effector, fungi, Lipid signaling, acide gras oméga 3, medicine.disease, maladie inflammatoire intestinale, 3. Good health, 030104 developmental biology, médiateur lipidique, Immunology, pharmacological activity, medicine.symptom, Resolvin, Polyunsaturated fatty acid
Abstract

The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPM) that limit the host response within the affected tissue; failure of effective resolution may lead to tissue injury. Because persistence of inflammatory signals is a main feature of chronic inflammatory conditions, including inflammatory bowel diseases (IBDs), herein we investigate expression and functions of SPM in intestinal inflammation. Targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was used to identify SPMs from n-3 polyunsaturated fatty acids in human IBD colon biopsies, quantifying a significant up-regulation of the resolvin and protectin pathway compared with normal gut tissue. Systemic treatment with protectin (PD)1n-3 DPA or resolvin (Rv)D5n-3 DPA protected against colitis and intestinal ischemia/reperfusion-induced inflammation in mice. Inhibition of 15-lipoxygenase activity reduced PD1n-3 DPA and augmented intestinal inflammation in experimental colitis. Intravital microscopy of mouse mesenteric venules demonstrated that PD1n-3 DPA and RvD5n-3 DPA decreased the extent of leukocyte adhesion and emigration following ischemia-reperfusion. These data were translated by assessing human neutrophil–endothelial interactions under flow: PD1n-3 DPA and RvD5n-3 DPA reduced cell adhesion onto TNF-α–activated human endothelial monolayers. In conclusion, we propose that innovative therapies based on n-3 DPA-derived mediators could be developed to enable antiinflammatory and tissue protective effects in inflammatory pathologies of the gut.

Published
2017
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8. Netrin-1 up-regulation in inflammatory bowel diseases is required for colorectal cancer progression

Author

Jean-Guy Delcros, Magali Svrcek, Carine Maisse, Nicolas Gadot, Jean-Yves Scoazec, Patrick Mehlen, Jean-François Fléjou, Florian Lepinasse, Clemens Neufert, Marie-May Coissieux, Andrea Paradisi, Céline Delloye-Bourgeois, Apoptose Cancer et Développement, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, ANIPATH, U865, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UMR S 893, Team 13 Microsatellite Instability and Cancers, Medical Clinic, Johannes Gutenberg - Universität Mainz (JGU), Institute for Molecular Medicine, Centre National de la Recherche Scientifique, Centre Leon Berard, Ligue Contre le Cancer, Institut National du Cancer, Agence Nationale de la Recherche, European Union Specific Targeted Research Projects Hermione and APOSYS : Association pour la Recherche contre le Cancer-Institut National du Cancer, and Association pour la Recherche contre le Cancer

Subjects
Colorectal cancer, [SDV]Life Sciences [q-bio], Apoptosis, Disease, souris, 0302 clinical medicine, Netrin, 0303 health sciences, Mice, Inbred BALB C, Multidisciplinary, évolution de la maladie, Caspase 3, NF-kappa B, cell line, Netrin-1, Biological Sciences, Ulcerative colitis, Immunohistochemistry, 3. Good health, Up-Regulation, reverse transcriptase polymerase chain reaction, lignée cellulaire, régulation positive des récepteurs, suppresseur de tumeur, cancer colorectal, 030220 oncology & carcinogenesis, Female, medicine.symptom, Colorectal Neoplasms, HT29 Cells, Signal Transduction, mice, Inflammation, transduction du signal, Mouse model of colorectal and intestinal cancer, 03 medical and health sciences, disease progression, Cell Line, Tumor, medicine, Animals, Humans, rt pcr, Nerve Growth Factors, Autocrine signalling, 030304 developmental biology, apoptose, business.industry, Tumor Suppressor Proteins, Cancer, medicine.disease, HCT116 Cells, Inflammatory Bowel Diseases, maladie inflammatoire intestinale, digestive system diseases, Immunology, Cancer research, business, colorectal neoplasm
Abstract

Chronic inflammation and cancer are intimately associated. This is particularly true for inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, which show a major increased risk for colorectal cancer. While the understanding of the molecular pathogenesis of IBD has recently improved, the mechanisms that link these chronic inflammatory states to colorectal cancer development are in large part unknown. One of these mechanisms is NF-κB pathway activation which in turn may contribute to tumor formation by providing anti-apoptotic survival signals to the epithelial cells. Based on the observation that netrin-1, the anti-apoptotic ligand for the dependence receptors DCC and UNC5H is up-regulated in colonic crypts in response to NF-κB, we show here that colorectal cancers from inflammatory bowel diseases patients have selected up-regulation of netrin-1. Moreover, we demonstrate that this inflammation-driven netrin-1 up-regulation is causal for colorectal cancer development as interference with netrin-1 autocrine loop in a mouse model for ulcerative colitis-associated colorectal cancer, while showing no effect on inflammation, inhibits colorectal cancer progression.

Published
2009
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9. Dietary Supplementation with a Low Dose of Polyphenol-Rich Grape Pomace Extract Prevents Dextran Sulfate Sodium-Induced Colitis in Rats

Author

Didier Fraisse, Bruno Pereira, Catherine Felgines, Marie-Paule Vasson, Ahlem Boussenna, Juliette Joubert-Zakeyh, Odile Texier, Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), 3inature Biosphère, Anatomie et cytologie pathologiques, CHU Clermont-Ferrand, Délégation à la Recherche Clinique et à l'Innovation (DRCI), 3inature Biosphere, Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and Centre Hospitalier Universitaire de Clermont-Ferrand

Subjects
Male, 0301 basic medicine, 040301 veterinary sciences, Anti-Inflammatory Agents, Medicine (miscellaneous), Inflammatory bowel disease, Antioxidants, aliment enrichi, 0403 veterinary science, 03 medical and health sciences, polyphénol, medicine, Animals, grape pomace extract, Vitis, Dietary supplementation, rat, Food science, Rats, Wistar, Colitis, Dextran Sulfate Sodium, Acute colitis, polyphenols, Peroxidase, marc de raisin, 030109 nutrition & dietetics, Nutrition and Dietetics, colon, Plant Extracts, Superoxide Dismutase, Chemistry, Dextran Sulfate, Low dose, fungi, Pomace, food and beverages, 04 agricultural and veterinary sciences, Inflammatory Bowel Diseases, medicine.disease, maladie inflammatoire intestinale, 3. Good health, Polyphenol, inflammation, Fruit, Dietary Supplements, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Phytotherapy, rôle protecteur
Abstract

Evidence from several epidemiological and experimental studies points to a beneficial role of dietary polyphenols in inflammatory bowel disease. In this study, we investigate the protective effect of dietary supplementation with various amounts of a polyphenol-rich grape pomace extract (GPE) on the development of dextran sulfate sodium (DSS)-induced colitis in rats. Rats were fed 21 days on a semisynthetic diet enriched with GPE (0.1%, 0.5%, and 1%), and acute colitis was induced by DSS (40 g/L in the drinking water) administration during the last 7 days. The low GPE content in the diet (0.1%) attenuated clinical signs and colon shortening and limited DSS-induced histological lesions. GPE 0.1% also attenuated the DSS-induced increase in myeloperoxidase activity and improved superoxide dismutase activity. Higher amounts of GPE in the diet induced only weak and nonsignificant protective effects. These results suggest that consumption of a low amount of polyphenol-rich GPE helps protect against colitis development.

Published
2016
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10. Identification of Metabolic Signatures Linked to Anti-Inflammatory Effects of Faecalibacterium prausnitzii

Author

Harry Sokol, Luis G. Bermúdez-Humarán, Chantal Bridonneau, Marion Leclerc, Trent R. Northen, Benjamin P. Bowen, Philippe Langella, Marion Lenoir, Sylvie Miquel, Florian Chain, Rebeca Martín, Sylvie Hudault, Sébastien Raguideau, Muriel Thomas, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Life Science Division [LBNL Berkeley], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), French group of faecal microbotia transplantation (FGFT), CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Gastroentérologie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vitagora Competitive Cluster, French FUI (Fond Unique Interministeriel) F1010012D, FEDER (Fonds Europeen de Developpement Regional) 34606, Burgundy Region, Conseil General 21, Grand Dijon, Merck Medication Familiale (Dijon, France), Biovitis (Saint Etienne de Chomeil, France), Langella, Philippe, MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Life Sciences Division, Lawrence Berkeley National Laboratory, Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), French group of faecal microbotia transplantation ( FGFT ), Gastroenterology and nutrition department, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Saint-Antoine [APHP], and Université Pierre et Marie Curie - Paris 6 ( UPMC )

Subjects
Male, Anti-Inflammatory Agents, Firmicutes, Faecalibacterium prausnitzii, Ileum, Biology, medicine.disease_cause, Microbiology, Feces, 03 medical and health sciences, Cecum, In vivo, Virology, medicine, Animals, Intestinal Mucosa, Colitis, Escherichia coli, Acute colitis, 030304 developmental biology, Mice, Inbred BALB C, 0303 health sciences, Gastrointestinal tract, 030306 microbiology, microbiote fécal, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, biology.organism_classification, maladie inflammatoire intestinale, QR1-502, 3. Good health, flore fécale, medicine.anatomical_structure, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, colite, Immunology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Blood Chemical Analysis, Research Article
Abstract

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood., IMPORTANCE Inflammatory bowel diseases (IBD) are characterized by low proportions of F. prausnitzii in the gut microbiome. This commensal bacterium exhibits anti-inflammatory effects through still unknown mechanisms. Stable monoassociated rodents are actually not a reproducible model to decipher F. prausnitzii protective effects. We propose a new gnotobiotic rodent model providing mechanistic clues. In this model, F. prausnitzii exhibits protective effects against an acute colitis and a protective metabolic profile is linked to its presence along the digestive tract. We identified a molecule, salicylic acid, directly involved in the protective effect of F. prausnitzii. Targeting its metabolic pathways could be an attractive therapeutic strategy in IBD.

Published
2015
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11. Faecalibacterium prausnitzii prevents physiological damages in a chronic low-grade inflammation murine model

Author

Harry Sokol, Philippe Langella, Jennifer Jury, Jun Lu, Florian Chain, Elena F. Verdu, Premysl Bercik, Jane M. Natividad, Rebeca Martín, Sylvie Miquel, Luis G. Bermúdez-Humarán, Vassilia Theodorou, MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Farncombe Family Digestive Health Research Institute, McMaster University [Hamilton, Ontario], Department of Medical Biochemistry and Biophysics, karolinska institute-Medical Nobel Institute for Biochemistry, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut national de la recherche agronomique [Toulouse] ( INRA Toulouse ), Vitagora Competitive Cluster, French FUI (Fond Unique Interministeriel, FUI) [F1010012D], FEDER (Fonds Europeen de Developpement Regional) [Bourgogne: 34606], Burgundy Region, Conseil General 21, Merck Medication Familiale (Dijon, France), Biovitis (Saint Etienne de Chomeil, France), CCFC grants, Grand Dijon, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 (UPMC), and Institut National de la Recherche Agronomique (INRA)

Subjects
Microbiology (medical), Serotonin, Colon, medicine.medical_treatment, Faecalibacterium prausnitzii, Inflammation, Biology, Low-grade inflammation, Microbiology, Permeability, law.invention, Enteritis, 03 medical and health sciences, Probiotic, Mice, IBD-remission, 0302 clinical medicine, law, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Colitis, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Microbiota, Dysbiosis, Probiotics, 0303 health sciences, Clostridiales, Intestinal permeability, Benzenesulfonates, probiotique, medicine.disease, biology.organism_classification, maladie inflammatoire intestinale, 3. Good health, Disease Models, Animal, Cytokine, microflore digestive, Immunology, Cytokines, 030211 gastroenterology & hepatology, bactérie intestinale, medicine.symptom, Research Article
Abstract

Background The human gut houses one of the most complex and abundant ecosystems composed of up to 1013-1014 microorganisms. The importance of this intestinal microbiota is highlighted when a disruption of the intestinal ecosystem equilibrium appears (a phenomenon called dysbiosis) leading to an illness status, such as inflammatory bowel diseases (IBD). Indeed, the reduction of the commensal bacterium Faecalibacterium prausnitzii (one of the most prevalent intestinal bacterial species in healthy adults) has been correlated with several diseases, including IBD, and most importantly, it has been shown that this bacterium has anti-inflammatory and protective effects in pre-clinical models of colitis. Some dysbiosis disorders are characterized by functional and physiological alterations. Here, we report the beneficial effects of F. prausnitzii in the physiological changes induced by a chronic low-grade inflammation in a murine model. Chronic low-grade inflammation and gut dysfunction were induced in mice by two episodes of dinitro-benzene sulfonic acid (DNBS) instillations. Markers of inflammation, gut permeability, colonic serotonin and cytokine levels were studied. The effects of F. prausnitzii strain A2-165 and its culture supernatant (SN) were then investigated. Results No significant differences were observed in classical inflammation markers confirming that inflammation was subclinical. However, gut permeability, colonic serotonin levels and the colonic levels of the cytokines IL-6, INF-γ, IL-4 and IL-22 were higher in DNBS-treated than in untreated mice. Importantly, mice treated with either F. prausnitzii or its SN exhibited significant decreases in intestinal permeability, tissue cytokines and serotonin levels. Conclusions Our results show that F. prausnitzii and its SN had beneficial effects on intestinal epithelial barrier impairment in a chronic low-grade inflammation model. These observations confirm the potential of this bacterium as a novel probiotic treatment in the management of gut dysfunction and low-grade inflammation. Electronic supplementary material The online version of this article (doi:10.1186/s12866-015-0400-1) contains supplementary material, which is available to authorized users.

Published
2015
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13. CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

Author

Guillaume Meurette, Chantal Bridonneau, Nathalie Labarrière, Anne Jarry, Francine Jotereau, Laurence Preisser, Joe-Marc Chauvin, Frédéric Altare, Karim Asehnoune, Guillaume Sarrabayrouse, Harry Sokol, Elodie Quévrain, Céline Bossard, Université de Nantes (UN), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Biomarqueurs prédictifs de la progression des metaplasies et dysplasies des epitheliums (Biométadys), Centre hospitalier universitaire de Nantes (CHU Nantes), Microorganismes, Molécules Bioactives et Physiopathologie Intestinale (LBM-E4), Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université d'Angers (UA), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Jarry, Anne, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inflammation intestinale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The work was supported by grants from FP7, ANR and Cancéropôle Grand Ouest 2009. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), CHU Saint-Antoine [APHP], Bernardo, Elizabeth, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Regulatory T cell, QH301-705.5, [SDV]Life Sciences [q-bio], réponse immunitaire, Faecalibacterium prausnitzii, cytométrie de flux, chemical and pharmacologic phenomena, Biology, Gut flora, lymphocyte, Inflammatory bowel disease, digestive system, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Intestinal mucosa, lymphocyte t, medicine, Biology (General), 030304 developmental biology, 0303 health sciences, General Immunology and Microbiology, General Neuroscience, FOXP3, hemic and immune systems, medicine.disease, biology.organism_classification, maladie inflammatoire intestinale, 3. Good health, [SDV] Life Sciences [q-bio], régulateur de réponse, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, monocyte, [SDV.IMM]Life Sciences [q-bio]/Immunology, clostridium, General Agricultural and Biological Sciences, Dysbiosis
Abstract

How the microbiota affects health and disease is a crucial question. In mice, gut Clostridium bacteria are potent inducers of colonic interleukin (IL)-10-producing Foxp3 regulatory T cells (Treg), which play key roles in the prevention of colitis and in systemic immunity. In humans, although gut microbiota dysbiosis is associated with immune disorders, the underlying mechanism remains unknown. In contrast with mice, the contribution of Foxp3 Treg in colitis prevention has been questioned, suggesting that other compensatory regulatory cells or mechanisms may exist. Here we addressed the regulatory role of the CD4CD8 T cells whose presence had been reported in the intestinal mucosa and blood. Using colonic lamina propria lymphocytes (LPL) and peripheral blood lymphocytes (PBL) from healthy individuals, and those with colon cancer and irritable bowel disease (IBD), we demonstrated that CD4CD8 (DP8) T lymphocytes expressed most of the regulatory markers and functions of Foxp3 Treg and secreted IL-10. Strikingly, DP8 LPL and PBL exhibited a highly skewed repertoire toward the recognition of Faecalibacterium prausnitzii, a major Clostridium species of the human gut microbiota, which is decreased in patients with IBD. Furthermore, the frequencies of DP8 PBL and colonic LPL were lower in patients with IBD than in healthy donors and in the healthy mucosa of patients with colon cancer, respectively. Moreover, PBL and LPL from most patients with active IBD failed to respond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors. These data (i) uncover a Clostridium-specific IL-10-secreting Treg subset present in the human colonic LP and blood, (ii) identify F. prausnitzii as a major inducer of these Treg, (iii) argue that these cells contribute to the control or prevention of colitis, opening new diagnostic and therapeutic strategies for IBD, and (iv) provide new tools to address the systemic impact of both these Treg and the intestinal microbiota on the human immune homeostasis. Author Summary It has become evident that bacteria in our gut affect health and disease, but less is known about how they do this. Recent studies in mice showed that gut Clostridium bacteria and their metabolites can activate regulatory T cells (Treg) that in turn mediate tolerance to signals that would ordinarily cause inflammation. In this study we identify a subset of human T lymphocytes, designated CD4CD8 T cells that are present in the surface lining of the colon and in the blood. We demonstrate Treg activity and show these cells to be activated by microbiota; we identify F. prausnitzii, a core Clostridium strain of the human gut microbiota, as a major inducer of these Treg cells. Interestingly, there are fewer F. prausnitzii in individuals suffering from inflammatory bowel disease (IBD), and accordingly the CD4CD8 T cells are decreased in the blood and gut of patients with IBD. We argue that CD4CD8 colonic Treg probably help control or prevent IBD. These data open the road to new diagnostic and therapeutic strategies for the management of IBD and provide new tools to address the impact of the intestinal microbiota on the human immune system.

Published
2014
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14. Deoxynivalenol as a new factor in the persistence of intestinal inflammatory diseases: An emerging hypothesis through possible modulation of Th17-mediated response

Author

Roberta Abrami, Laurence Guzylack-Piriou, François Meurens, Patricia M. Cano, Isabelle P. Oswald, Juliette Cognie, Julie Seeboth, Toxicologie Alimentaire (UTA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Vaccine and Infectious Disease Organization, University of Saskatchewan [Saskatoon] (U of S), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), INRA, ANSES (France), Ministry for Education and Research (France), CAPES-COFECUB (Brazil), INRA-Division of animal health, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), State University of Londrina = Universidade Estadual de Londrina, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Oswald, Isabelle, Guzylack-Piriou, Laurence, Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Toxicologie Alimentaire ( UTA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, UR Infectiologie animale et Santé publique ( UR IASP ), Institut National de la Recherche Agronomique ( INRA ), University of Saskatchewan [Saskatoon] ( U of S ), Physiologie de la reproduction et des comportements [Nouzilly] ( PRC ), and Institut National de la Recherche Agronomique ( INRA ) -Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique ( CNRS )

Subjects
Chemokine, Anatomy and Physiology, système immunitaire, Sus scrofa, Digestive Physiology, Veterinary Toxicology, deoxynivalenol, lcsh:Medicine, Toxicology, T-Lymphocytes, Regulatory, Persistence (computer science), Immune tolerance, chemistry.chemical_compound, Immunotoxicology, Immune Physiology, Intestinal Mucosa, lcsh:Science, Immune Response, 0303 health sciences, Multidisciplinary, T Cells, santé animale, 030302 biochemistry & molecular biology, food and beverages, rt pcr quantitative, 3. Good health, Inflammatory mediator, Intestines, Jejunum, Veterinary Diseases, Veterinary Mycology, Models, Animal, Cytokines, medicine.symptom, Chemokines, Inflammation Mediators, Research Article, Autre (Sciences du Vivant), [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], analyse protéomique, mycotoxine, Immune Cells, Animal Types, Immunology, Toxic Agents, Inflammation, Immunopathology, Biology, In Vitro Techniques, Large Animals, Cell Line, Immunomodulation, 03 medical and health sciences, arn, Immune system, medicine, Animals, RNA, Messenger, [ SDV.OT ] Life Sciences [q-bio]/Other [q-bio.OT], Mycotoxin, 030304 developmental biology, Gene Expression Profiling, lcsh:R, Dendritic Cells, maladie inflammatoire intestinale, étude transcriptomique, chemistry, Gene Expression Regulation, santé publique, biology.protein, Th17 Cells, Digestive tract, Veterinary Science, lcsh:Q, Trichothecenes, Digestive System
Abstract

Background/Aims: Deoxynivalenol (DON) is a mycotoxin produced by Fusarium species which is commonly found in temperate regions worldwide as a natural contaminant of cereals. It is of great concern not only in terms of economic losses but also in terms of animal and public health. The digestive tract is the first and main target of this food contaminant and it represents a major site of immune tolerance. A finely tuned cross-talk between the innate and the adaptive immune systems ensures the homeostatic equilibrium between the mucosal immune system and commensal microorganisms. The aim of this study was to analyze the impact of DON on the intestinal immune response. Methodology: Non-transformed intestinal porcine epithelial cells IPEC-1 and porcine jejunal explants were used to investigate the effect of DON on the intestinal immune response and the modulation of naive T cells differentiation. Transcriptomic proteomic and flow cytometry analysis were performed. Results: DON induced a pro-inflammatory response with a significant increase of expression of mRNA encoding for IL-8, IL-1 alpha and IL-1 beta, TNF-alpha in all used models. Additionally, DON significantly induced the expression of genes involved in the differentiation of Th17 cells (STAT3, IL-17A, IL-6, IL-1 beta) at the expenses of the pathway of regulatory T cells (Treg) (FoxP3, RALDH1). DON also induced genes related to the pathogenic Th17 cells subset such as IL-23A, IL-22 and IL-21 and not genes related to the regulatory Th17 cells (rTh17) such as TGF-beta and IL-10. Conclusion: DON triggered multiple immune modulatory effects which could be associated with an increased susceptibility to intestinal inflammatory diseases.

Published
2013
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15. Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon

Author

Geneviève Gramet, Philippe Seksik, P Marteau, Joël Doré, P Pochart, R. Jian, Malène Sutren, Lionel Rigottier-Gois, Unité de recherche d'Écologie et Physiologie du Système Digestif (UEPSD), Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biologie, Conservatoire National des Arts et Métiers [CNAM] (CNAM), and Bactéries Lactiques et Pathogènes Opportunistes (UBLO)

Subjects
Male, [SDV]Life Sciences [q-bio], microflore, Dot blot, TUBE DIGESTIF, biodiversité, Feces, Crohn Disease, diversité microbienne, Bacteroides, électrophorèse, ComputingMilieux_MISCELLANEOUS, Bifidobacterium, biology, Gastroenterology, Ileitis, Middle Aged, Colitis, Enterobacteriaceae, homme, RNA, Bacterial, Female, Temperature gradient gel electrophoresis, Adult, DNA, Bacterial, HYBRIDATION EN DOT BLOT, Adolescent, entérobactérie, DNA, Ribosomal, Microbiology, stomatognathic system, Humans, analyse moléculaire, Aged, Clostridium, colon, Bacteria, Inflammation and Inflammatory Bowel Disease, maladie de crohn, Ribosomal RNA, biology.organism_classification, 16S ribosomal RNA, maladie inflammatoire intestinale, digestive system diseases, stomatognathic diseases, Lactobacillus, flore fécale, inflammation, RNA, Ribosomal
Abstract

Background and aim: The colonic microflora is involved in the pathogenesis of Crohn9s disease (CD) but less than 30% of the microflora can be cultured. We investigated potential differences in the faecal microflora between patients with colonic CD in remission (n=9), patients with active colonic CD (n=8), and healthy volunteers (n=16) using culture independent techniques. Methods: Quantitative dot blot hybridisation with six radiolabelled 16S ribosomal ribonucleic acid (rRNA) targeting oligonucleotide probes was used to measure the proportions of rRNA corresponding to each phylogenetic group. Temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA was used to evaluate dominant species diversity. Results: Enterobacteria were significantly increased in active and quiescent CD. Probe additivity was significantly lower in patients (65 (11)% and 69 (6)% in active CD and quiescent CD) than in healthy controls (99 (7)%). TTGE profiles varied markedly between active and quiescent CD but were stable in healthy conditions. Conclusion: The biodiversity of the microflora remains high in patients with CD. Enterobacteria were observed significantly more frequently in CD than in health, and more than 30% of the dominant flora belonged to yet undefined phylogenetic groups.

Published
2003

16. Embolic lower limb ischemia as a rare complication of ulcerative colitis: A case report and literature review.

Author

Zizi O, Benfor B, Jiber H, and Bouarhroum A

Subjects
Adrenal Cortex Hormones therapeutic use, Balloon Embolectomy, Humans, Male, Middle Aged, Thromboembolism surgery, Warfarin therapeutic use, Colitis, Ulcerative complications, Ischemia etiology, Lower Extremity blood supply, Thromboembolism complications
Abstract

Thromboembolic events in chronic inflammatory bowel diseases are rare and predominated by venous damage. Arterial thromboembolic events are extremely uncommon. We are reporting the case of a 50-year-old male patient with an 8-year history of ulcerative colitis, who presented a recurring severe lower limb ischemia during hospital stay for exacerbation of his inflammatory bowel disease. During the first visit, the patient underwent a balloon thromboembolectomy via femoral approach, with fasciotomy of the leg. Because of recurrence of symptoms, he underwent a second and a third thromboembolectomy by a popliteal approach, with an uneventful postoperative course and was discharged home 10 days later, on warfarin therapy and oral corticosteroids. After an extensive literature review using PubMed, we found 20 reported cases in the English literature over the past 25 years; not including this present case. In the absence of major cardiovascular risk factors, inherited thrombophilia and intracardiac thrombi, we consider active ulcerative colitis to be the major trigger of the embolic lower limb ischemia in our patient. By means of this report, we seek to create awareness of the increased risk of arterial thromboembolism in inflammatory bowel diseases patients., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Published
2016
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