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1. Detection of Ulcerative Colitis Lesions from Weakly Annotated Colonoscopy Videos Using Bounding Boxes

Author: Safaa Al-Ali, John Chaussard, Sébastien Li-Thiao-Té, Éric Ogier-Denis, Alice Percy-du-Sert, Xavier Treton, and Hatem Zaag
Subjects: bleeding, bounding box annotation, lesion detection, model selection, sensitivity, ulcer, Medicine, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Ulcerative colitis is a chronic disease characterized by bleeding and ulcers in the colon. Disease severity assessment via colonoscopy videos is time-consuming and only focuses on the most severe lesions. Automated detection methods enable fine-grained assessment but depend on the training set quality. To suit the local clinical setup, an internal training dataset containing only rough bounding box annotations around lesions was utilized. Following previous works, we propose to use linear models in suitable color spaces to detect lesions. We introduce an efficient sampling scheme for exploring the set of linear classifiers and removing trivial models i.e., those showing zero false negative or positive ratios. Bounding boxes lead to exaggerated false detection ratios due to mislabeled pixels, especially in the corners, resulting in decreased model accuracy. Therefore, we propose to evaluate the model sensitivity on the annotation level instead of the pixel level. Our sampling strategy can eliminate up to 25% of trivial models. Despite the limited quality of annotations, the detectors achieved better performance in comparison with the state-of-the-art methods. When tested on a small subset of endoscopic images, the best models exhibit low variability. However, the inter-patient model performance was variable suggesting that appearance normalization is critical in this context.
Published: 2024
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2. Systemically delivered adipose stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome by immunomodulating the inflammatory response through a CD11b+ cell-dependent mechanism

Author: Lydia Bensemmane, Fabien Milliat, Xavier Treton, and Christine Linard
Subjects: Stromal vascular fraction, Intestine, Irradiation, Monocyte, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract: Abstract Background Stromal vascular fraction (SVF) treatment promoted the regeneration of the intestinal epithelium, limiting lethality in a mouse model of radiation-induced gastrointestinal syndrome (GIS). The SVF has a heterogeneous cell composition; the effects between SVF and the host intestinal immunity are still unknown. The specific role of the different cells contained in the SVF needs to be clarified. Monocytes–macrophages have a crucial role in repair and monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2. Methods Mice exposed to abdominal radiation (18 Gy) received a single intravenous injection of SVF (2.5 × 106 cells), obtained by enzymatic digestion of inguinal fat tissue, on the day of irradiation. Intestinal immunity and regeneration were evaluated by flow cytometry, RT-PCR and histological analyses. Results Using flow cytometry, we showed that SVF treatment modulated intestinal monocyte differentiation at 7 days post-irradiation by very early increasing the CD11b+Ly6C+CCR2+ population in the intestine ileal mucosa and accelerating the phenotype modification to acquire CX3CR1 in order to finally restore the F4/80+CX3CR1+ macrophage population. In CX3CR1-depleted mice, SVF treatment fails to mature the Ly6C−MCHII+CX3CR1+ population, leading to a macrophage population deficit associated with proinflammatory environment maintenance and defective intestinal repair; this impaired SVF efficiency on survival. Consistent with a CD11b+ being involved in SVF-induced intestinal repair, we showed that SVF-depleted CD11b+ treatment impaired F4/80+CX3CR1+macrophage pool restoration and caused loss of anti-inflammatory properties, abrogating stem cell compartment repair and survival. Conclusions These data showed that SVF treatment mitigates the GIS-involving immunomodulatory effect. Cooperation between the monocyte in SVF and the host monocyte defining the therapeutic properties of the SVF is necessary to guarantee the effective action of the SVF on the GIS.
Published: 2023
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3. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated CancerSummary

Author: Maxime K. Collard, Julien Tourneur-Marsille, Mathieu Uzzan, Miguel Albuquerque, Maryline Roy, Anne Dumay, Jean-Noël Freund, Jean-Pierre Hugot, Nathalie Guedj, Xavier Treton, Yves Panis, and Eric Ogier-Denis
Subjects: Appendectomy, Appendicitis, Ulcerative Colitis, Inflammatory Bowel Disease, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Although appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), this surgical procedure has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). Our aim was to explore the mechanism underlying the appendectomy-associated increased risk of CAC. Methods: Five-week-old male BALB/c mice underwent appendectomy, appendicitis induction, or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were killed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 patients with UC who underwent surgical resection for CAC were immunophenotyped and stratified according to appendectomy status. Results: Whereas appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intratumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared with the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors’ number and on CD3+/CD8+ intratumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intratumor CD3+ and CD8+ T-cell densities were decreased compared with UC patients without history of appendectomy. Conclusions: In UC, appendectomy could suppress a major site of T-cell priming, resulting in a less efficient CAC immunosurveillance.
Published: 2023
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4. The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis

Author: Jorge Mata-Garrido, Yao Xiang, Yunhua Chang-Marchand, Caroline Reisacher, Elisabeth Ageron, Ida Chiara Guerrera, Iñigo Casafont, Aurelia Bruneau, Claire Cherbuy, Xavier Treton, Anne Dumay, Eric Ogier-Denis, Eric Batsché, Mickael Costallat, Gwladys Revêchon, Maria Eriksson, Christian Muchardt, and Laurence Arbibe
Subjects: Science
Abstract: This study reports reduced expression of the chromatin and splicing regulator HP1γ in inflammatory bowel disease (IBD) and shows that HP1γ protects against pervasive RNA splicing leading to toxic mRNA products detected in IBD, like progerin.
Published: 2022
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5. Fecal microbiota and bile acids in IBD patients undergoing screening for colorectal cancer

Author: Aonghus Lavelle, Stéphane Nancey, Jean-Marie Reimund, David Laharie, Philippe Marteau, Xavier Treton, Matthieu Allez, Xavier Roblin, Georgia Malamut, Cyriane Oeuvray, Nathalie Rolhion, Xavier Dray, Dominique Rainteau, Antonin Lamaziere, Emilie Gauliard, Julien Kirchgesner, Laurent Beaugerie, Philippe Seksik, Laurent Peyrin-Biroulet, and Harry Sokol
Subjects: Gut microbiota, inflammatory bowel disease, dysplasia, colitis-associated colorectal cancer, crohn’s disease, ulcerative colitis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Due to the potential role of the gut microbiota and bile acids in the pathogenesis of both inflammatory bowel disease (IBD) and sporadic colorectal cancer, we aimed to determine whether these factors were associated with colorectal cancer in IBD patients. 215 IBD patients and 51 non-IBD control subjects were enrolled from 10 French IBD centers between September 2011 and July 2018. Fecal samples were processed for bacterial 16S rRNA gene sequencing and bile acid profiling. Demographic, clinical, endoscopic, and histological outcomes were recorded. Characteristics of IBD patients included: median age: 41.6 (IQR 22); disease duration 13.2 (13.1); 47% female; 21.9% primary sclerosing cholangitis; 109 patients with Crohn’s disease (CD); 106 patients with ulcerative colitis (UC). The prevalence of cancer was 2.8% (6/215: 1 CD; 5 UC), high-grade dysplasia 3.7% (8/215) and low-grade dysplasia 7.9% (17/215). Lachnospira was decreased in IBD patients with cancer, while Agathobacter was decreased and Escherichia-Shigella increased in UC patients with any neoplasia. Bile acids were not associated with cancer or neoplasia. Unsupervised clustering identified three gut microbiota clusters in IBD patients associated with bile acid composition and clinical features, including a higher risk of neoplasia in UC in two clusters when compared to the third (relative risk (RR) 4.07 (95% CI 1.6–10.3, P
Published: 2022
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6. Impact of panelists’ experience on script concordance test scores of medical students

Author: Olivier Peyrony, Alice Hutin, Jennifer Truchot, Raphaël Borie, David Calvet, Adrien Albaladejo, Yousrah Baadj, Pierre-Emmanuel Cailleaux, Martin Flamant, Clémence Martin, Jonathan Messika, Alexandre Meunier, Mariana Mirabel, Victoria Tea, Xavier Treton, Sylvie Chevret, David Lebeaux, and Damien Roux
Subjects: Script concordance test, Medical student, Panelist, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. Methods In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. Results A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students’ SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p
Published: 2020
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7. Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation

Author: Marion Maurel, Joanna Obacz, Tony Avril, Yong‐Ping Ding, Olga Papadodima, Xavier Treton, Fanny Daniel, Eleftherios Pilalis, Johanna Hörberg, Wenyang Hou, Marie‐Claude Beauchamp, Julien Tourneur‐Marsille, Dominique Cazals‐Hatem, Lucia Sommerova, Afshin Samali, Jan Tavernier, Roman Hrstka, Aurélien Dupont, Delphine Fessart, Frédéric Delom, Martin E Fernandez‐Zapico, Gregor Jansen, Leif A Eriksson, David Y Thomas, Loydie Jerome‐Majewska, Ted Hupp, Aristotelis Chatziioannou, Eric Chevet, and Eric Ogier‐Denis
Subjects: AGR2, endoplasmic reticulum, inflammation, proteostasis, TMED2, Medicine (General), R5-920, Genetics, QH426-470
Abstract: Abstract Anterior gradient 2 (AGR2) is a dimeric protein disulfide isomerase family member involved in the regulation of protein quality control in the endoplasmic reticulum (ER). Mouse AGR2 deletion increases intestinal inflammation and promotes the development of inflammatory bowel disease (IBD). Although these biological effects are well established, the underlying molecular mechanisms of AGR2 function toward inflammation remain poorly defined. Here, using a protein–protein interaction screen to identify cellular regulators of AGR2 dimerization, we unveiled specific enhancers, including TMED2, and inhibitors of AGR2 dimerization, that control AGR2 functions. We demonstrate that modulation of AGR2 dimer formation, whether enhancing or inhibiting the process, yields pro‐inflammatory phenotypes, through either autophagy‐dependent processes or secretion of AGR2, respectively. We also demonstrate that in IBD and specifically in Crohn's disease, the levels of AGR2 dimerization modulators are selectively deregulated, and this correlates with severity of disease. Our study demonstrates that AGR2 dimers act as sensors of ER homeostasis which are disrupted upon ER stress and promote the secretion of AGR2 monomers. The latter might represent systemic alarm signals for pro‐inflammatory responses.
Published: 2019
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8. A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn’s Disease

Author: Antoine Cazelles, Maxime K. Collard, Yoann Lalatonne, Sabrina Doblas, Magaly Zappa, Camélia Labiad, Dominique Cazals-Hatem, Léon Maggiori, Xavier Treton, Yves Panis, Ulrich Jarry, Thomas Desvallées, Pierre-Antoine Eliat, Raphaël Pineau, Laurence Motte, Didier Letourneur, Teresa Simon-Yarza, and Eric Ogier-Denis
Subjects: Crohn’s disease, perianal fistula, preclinical model, iron oxide nanoparticles, fistula treatment, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Fistulizing anoperineal lesions are severe complications of Crohn’s disease (CD) that affect quality of life with a long-term risk of anal sphincter destruction, incontinence, permanent stoma, and anal cancer. Despite several surgical procedures, they relapse in about two-thirds of patients, mandating innovative treatments. Ultrasmall particles of iron oxide (USPIO) have been described to achieve in vivo rapid healing of deep wounds in the skin and liver of rats thanks to their nanobridging capability that could be adapted to fistula treatment. Our main purpose was to highlight preclinical data with USPIO for the treatment of perianal fistulizing CD. Twenty male Sprague Dawley rats with severe 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced proctitis were operated to generate two perianal fistulas per rat. At day 35, two inflammatory fistulas were obtained per rat and perineal magnetic resonance imaging (MRI) was performed. After a baseline MRI, a fistula tract was randomly drawn and topically treated either with saline or with USPIO for 1 min (n = 17 for each). The rats underwent a perineal MRI on postoperative days (POD) 1, 4, and 7 and were sacrificed for pathological examination. The primary outcome was the filling or closure of the fistula tract, including the external or internal openings. USPIO treatment allowed the closure and/or filling of all the treated fistulas from its application until POD 7 in comparison with the control fistulas (23%). The treatment with USPIO was safe, permanently closed the fistula along its entire length, including internal and external orifices, and paved new avenues for the treatment of perianal fistulizing Crohn’s disease.
Published: 2022
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9. I-FABP is decreased in COVID-19 patients, independently of the prognosis.

Author: Kevin Guedj, Mathieu Uzzan, Damien Soudan, Catherine Trichet, Antonino Nicoletti, Emmanuel Weiss, Hana Manceau, Alexandre Nuzzo, Olivier Corcos, Xavier Treton, and Katell Peoc'h
Subjects: Medicine, Science
Abstract: BackgroundSevere acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) is frequently associated with gastrointestinal manifestations. Herein we evaluated the interest in measuring the intestinal fatty acid-binding protein (I-FABP), a biomarker of intestinal injury, in COVID-19 patients.MethodsSerum I-FABP was analyzed in 28 consecutive patients hospitalized for a PCR-confirmed COVID-19, in 24 hospitalized patients with non-COVID-19 pulmonary diseases, and 79 patients admitted to the emergency room for abdominal pain.ResultsI-FABP serum concentrations were significantly lower in patients with COVID-19, as compared to patients with non-COVID-19 pulmonary diseases [70.3 pg/mL (47-167.9) vs. 161.1 pg/mL (88.98-305.2), respectively, p = 0.008]. I-FABP concentrations in these two populations were significantly lower than in patients with abdominal pain without COVID-19 [344.8 pg/mL (268.9-579.6)]. I-FABP was neither associated with severity nor the duration of symptoms. I-FABP was correlated with polymorphonuclear cell counts.ConclusionsIn this pilot study, we observed a low I-FABP concentration in COVID-19 patients either with or without gastrointestinal symptoms, of which the pathophysiological mechanisms and clinical impact remain to be established. Further explorations on a larger cohort of patients will be needed to unravel the molecular mechanism of such observation, including the effects of malabsorption and/or abnormal lipid metabolism.
Published: 2021
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10. Adalimumab in biologic-naïve patients with Crohn’s disease after resolution of an intra-abdominal abscess: a prospective study from the GETAID

Author: Yoram Bouhnik, Guillaume Pineton de Chambrun, Jérôme Lambert, Maria Nachury, Philippe Seksik, Romain Altwegg, Lucine Vuitton, Carmen Stefanescu, Stéphane Nancey, Alexandre Aubourg, Mélanie Serrero, Jérôme Filippi, Kristell Desseaux, Stéphanie Viennot, Vered Abitbol, Madina Boualit, Arnaud Bourreille, Cyrielle Giletta, Anthony Buisson, Xavier Roblin, Nina Dib, Georgia Malamut, Aurélien Amiot, Mathurin Fumery, Edouard Louis, Yasmine Elgharabawy, Laurent Peyrin-Biroulet, Jacques Moreau, Xavier Treton, Charlotte Mailhat, Justine Pollet, Carole Martins, Guillaume Savoye, Noémie Tavernier, Jean-Yves Mary, Magali Zappa, Claire Painchart, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hopital Saint-Louis [AP-HP] (AP-HP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Nord [CHU - APHM], Centre Hospitalier Universitaire de Nice (CHU Nice), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), and Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: Crohn’s disease, surgery, Hepatology, adalimumab, Gastroenterology, abscess, anti-TNF, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background & aims: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in CD patients with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success.Methods: A multicenter, prospective study was conducted in biologic-naïve CD patients with resolved intra-abdominal abscess treated with ADA with a two-year follow-up. The primary endpoint was ADA failure at W24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a cox regression, respectively.Results: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight (50%) patients were male and the median age at baseline was 28 years. At W24, 87 (74%, 95%CI: 65.5-82.0, n=117) patients achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72·9% (95%CI: 62.1-79.8, n=109). Abscess drainage was significantly associated with ADA failure at W24 (OR=4.18; 95%CI: 1.06-16.5; p=0.043). Disease duration (HR=1.32, 95%CI: 1.09-1.59, p=0.008), abscess drainage (HR=5.59, 95%CI: 2.21-14.15, p=0.001), and inflammatory changes in mesenteric fat (HR=0.4, 95%CI: 0.17-0.94, p=0.046) were significantly associated with ADA failure at W104.Conclusion: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess.
Published: 2023

11. Prevalence of anti-TNF contraindications in Crohn’s disease: A cross-sectional survey from the GETAID

Author: Aurelien Amiot, Philippe Seksik, Jean-Marie Reimund, Maria Nachury, Romain Altwegg, Arnaud Bourreille, Stephanie Viennot, Mathurin Fumery, Xavier Roblin, Melanie Serrero, Matthieu Allez, Claire Painchart, Elise Chanteloup, Lucine Vuitton, Ginette Fotsing, Anthony Buisson, Baya Coulibaly, Stephane Nancey, Cyrielle Gilletta, Laurianne Plastaras, Vered Abitbol, Lucas Guillo, Marion Simon, Stephane Nahon, David Laharie, Laurent Peyrin-Biroulet, Guillaume Bouguen, Charlotte Gagniere, Pauline Wils, Yoram Bouhnik, Carmen Stefanescu, Xavier Treton, Carole Martins, Mathieu Uzzan, Emilie Del Tedesco, Laurent Beaugerie, Anne Bourrier, Cecilia Landmann, Julien Kirchgesner, Harry Sokol, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Medina Boualit, Lucile Boivineau, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Hospital of Montpellier, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Aix Marseille Université (AMU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier [Valenciennes, Nord], Hôpital Saint-Joseph [Marseille], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Clermont-Ferrand, Centre Hospitalier Henri Duffaut (Avignon), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CH Colmar, Hôpital Cochin [AP-HP], Institut Mutualiste de Montsouris (IMM), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, CHU Bordeaux [Bordeaux], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], This study was supported by an institutional grant by Takeda, CRHU Nancy, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Saint-Etienne, and CHU Toulouse [Toulouse]
Subjects: Crohn’s disease, Hepatology, Contraindications, [SDV]Life Sciences [q-bio], Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Inflammatory bowel disease, Anti-TNF, Cross-Sectional Studies, Treatment Outcome, Crohn Disease, Prevalence, Humans, Tumor Necrosis Factor Inhibitors, Ustekinumab, Contraindication
Abstract: International audience; BACKGROUND: The exact rate of contraindications to anti-TNF therapy and physician perspectives on treatment choices facing to anti-TNF contraindication, are poorly reported. METHODS: A two-week cross-sectional study was conducted in 31 centres. Physicians completed a questionnaire for a total of 1,314 consecutive outpatients with Crohn’s disease, assessing each patient’s potential contraindications to anti-TNF therapy, the choice of alternative therapy to anti-TNFs, and their preference in an unrestricted reimbursement setting. RESULTS: Among the 1,293 responses to the first item, 148 (11.5%) reported 32 absolute contraindications (2.5%) and 116 relative contraindications (9.0%) to anti-TNF therapy. When asked about their preference of alternative therapies in those cases with contraindications to anti-TNF, physicians chose ustekinumab and vedolizumab, 75.6% and 23.9%, respectively. In multivariable analysis, the choice of vedolizumab was the preferred choice for patients aged > 60 years with the L2 phenotype and the absence of perianal lesions. In a hypothetical setting of unrestricted reimbursement, anti-TNFs remained physicians’ preferred first-line biological therapy choice for 78.2%. CONCLUSION: Anti-TNF contraindications occurred in up to 11.5% of patients with Crohn’s disease. Physicians’ choices for alternative therapy to anti-TNF relied on ustekinumab in 75.6% and vedolizumab in 23.9% of these cases. This choice was driven mainly by phenotypical criteria and age.
Published: 2022

12. Role of adherent and invasive Escherichia coli in Crohn’s disease: lessons from the postoperative recurrence model

Author: Anthony Buisson, Harry Sokol, Nassim Hammoudi, Stéphane nancey, Xavier Treton, Maria Nachury, Mathurin Fumery, Xavier Hébuterne, Michael Rodrigues, Jean-Pierre Hugot, Gilles Boschetti, Carmen Stefanescu, Pauline Wils, Philippe Seksik, Lionel Le Bourhis, Madeleine Bezault, Pierre Sauvanet, Bruno Pereira, Matthieu Allez, Nicolas Barnich, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Servcie Hépato-gastroentérolgie et Nutrition clinique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Remind Study Group, Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], Unité de Biostatistiques [CHU Clermont-Ferrand], MSD France, Association François Aupetit, Helmsley Charitable Trust, Ministère de la Recherche et de la Technologie, Inserm (UMR 1071), University of Clermont Auvergne, Inserm {National Programme 'Microbiote'], INRAE (USC-2018), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)
Subjects: Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: ObjectiveWe used the postoperative recurrence model to better understand the role of adherent and invasiveEscherichia coli(AIEC) bacteria in Crohn’s disease (CD), taking advantage of a well-characterised postoperative cohort.DesignFrom a prospective, multicentre cohort of operated patients with CD, AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neoterminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts’ index. The mucosa-associated microbiota was analysed by 16S sequencing at M0 and M6. Relative risks or ORs were adjusted on potential confounders.ResultsAIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (pRuminococcus gnavus.ConclusionBased on the postoperative recurrence model, our data support the idea that AIEC are involved in the early steps of ileal CD.Trial registration numberNCT03458195.
Published: 2022

13. Real‐world comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis exposed to at least one anti‐ TNF agent

Author: Anthony Buisson, Maria Nachury, Thomas Guilmoteau, Romain Altwegg, Xavier Treton, Mathurin Fumery, Melanie Serrero, Eloïse Leclerc, Ludovic Caillo, Bruno Pereira, Aurélien Amiot, Guillaume Bouguen, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Hôpital Nord [CHU - APHM], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Unité de Biostatistiques [CHU Clermont-Ferrand], Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Pfilzer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Hepatology, Gastroenterology, Pharmacology (medical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Data comparing tofacitinib and vedolizumab in ulcerative colitis (UC) are lacking.Aims: To compare the effectiveness of tofacitinib and vedolizumab in patients with UC who had prior exposure to anti-TNF therapy METHODS: In this multicentre study, we included consecutive patients with UC ≥18 years old with partial Mayo score >2 and prior anti-TNF exposure, who started tofacitinib or vedolizumab between January 2019 and June 2021. Comparisons were performed using propensity score analyses (inverse probability of treatment weighting).Results: Overall, 126 and 178 patients received tofacitinib and vedolizumab, respectively. Intensified induction (vedolizumab infusion at week 10 or tofacitinib 10 mg b.d until week 16) was performed in 28.5% and 41.5% of patients, respectively. After propensity-score analysis, corticosteroid-free clinical remission (partial Mayo score ≤2) was achieved at week 16 in 45.1% and 40.2% of patients receiving tofacitinib and vedolizumab, respectively (aOR = 0.82 [0.35-1.91], p = 0.64). Endoscopic improvement (corticosteroid-free clinical remission and endoscopic Mayo score ≤1) (aOR = 0.23[0.08-0.65], p = 0.0032) and histological healing (endoscopic improvement + Nancy histological index ≤1) (13.4% vs 3.2%, aOR = 0.21[0.05-0.91], p = 0.023) were higher at week 16 in patients treated with tofacitinib. No factor was predictive of tofacitinib effectiveness. At least one primary failure to a biologic (OR = 0.46[0.22-0.99], p = 0.049), partial Mayo score >6 (OR = 0.39[0.17-0.90], p = 0.029) and CRP level > 30 mg/L at baseline (OR = 0.08[0.01-0.85], p = 0.036) were associated with vedolizumab failure.Conclusion: Tofacitinib and vedolizumab are effective in UC after failure of anti-TNF agents. However, tofacitinib seems more effective, especially in severe disease and primary failure to biologics.
Published: 2022

14. The Heterochromatin protein 1 is a master regulator in RNA splicing precision deficient in ulcerative colitis

Author: Jorge Mata-Garrido, Yao Xiang, Yunhua Chang-Marchand, Caroline Reisacher, Elisabeth Ageron-ardila, Chiara Guerrera, Inigo Casafont, Aurelia Bruneau, Claire Cherbuy, Xavier Treton, Anne Dumay, Eric Ogier-Denis, Eric Batsche, Mickael Costallat, Gwladys Revêchon, Maria Eriksson, Christian Muchardt, Laurence Arbibe, Batsche, Eric, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Universidad de Cantabria [Santander], Unité de recherche d'Écologie et Physiologie du Système Digestif (UEPSD), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Karolinska Institutet [Stockholm]
Subjects: Heterochromatin protein, integumentary system, [SDV]Life Sciences [q-bio], master regulator, RNA, Biology, Progerin, Intestinal epithelium, Gut Epithelium, Cell biology, LMNA, [SDV] Life Sciences [q-bio], Ageing, Ectopic expression, Epigenetics
Abstract: Defects in RNA splicing have been linked to numerous human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that, in the gut epithelium of patients with ulcerative colitis (UC), the expression of the chromatin and alternative splicing regulator HP1γ is strongly reduced. Accordingly, inactivation of the HP1γ gene in the mouse gut triggered several IBD-like traits, including inflammation and dysbiosis. In parallel, we discovered that its loss of function broadly increased splicing noise, reducing requirement for canonical splicing consensus sequences, and favoring the usage of cryptic splice sites at numerous genes with key functions in gut biology. This notably resulted in the production of progerin, a noncanonical toxic splice variant of prelamin A mRNA, responsible for the Hutchinson Gilford Progeria Syndrome (HGPS) of premature aging. Likewise, production of progerin transcript was found to be a signature of colonic cells from UC patients. Thus, our study identifies HP1γ as a regulator of RNA metabolism in vivo, providing a unique mechanism linking anti-inflammation and accuracy of RNA splicing in the gut epithelium. HP1 defect may confer a general disturbance in RNA splicing precision to scrutinize in IBD and more generally in accelerating aging diseases.
Published: 2022

15. Patients’ real-world experience with inflammatory bowel disease: A cross-sectional survey in tertiary care centres from the GETAID group

Author: Maria Nachury, Yoram Bouhnik, Melanie Serrero, Jerome Filippi, Xavier Roblin, Julien Kirchgesner, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered Abitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Matthieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Sara Tadbiri, Matthieu Allez, Stephanie Viennot, Arnaud Bourreille, David Laharie, Aurelien Amiot, Charlotte Gagniere, Jenny Tannoury, Benjamin Pariente, Pauline Wils, Carmen Stefanescu, Xavier Treton, Xavier Hébuterne, Nadia Arab, Virginie Cluzeau, Emilie Del Tedesco, Laurent Beaugerie, Philippe Seksik, Anne Bourrier, Cecilia Landmann, Harry Sokol, Laurent Siproudhis, Marie DeWitte, Catherine Reenaers, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Olivier DeWitt, Nicolas Mathieu, Sandie Pestour, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Nina Dib, Hedi Brixi, Guillaume Cadiot, Medina Boualit, Claire Painchart, Laurianne Plastaras, Romain Altwegg, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Stephane Nahon, Noemie Tavernier, Marion Simon, Baya Coulibaly, Morgane Amil, Duveau Nicolas, Sherine Khater, Mehdi Kaassis, Felix Goutorbe, Driffa Moussata, Laurence Picon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pasteur [Nice] (CHU), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan), AbbVie, GETAID-patient experience study group: Aurelien Amiot , Sara Tadbiri , Charlotte Gagniere , Jenny Tannoury , Maria Nachury , Benjamin Pariente , Pauline Wils , Yoram Bouhnik , Carmen Stefanescu , Xavier Treton , Melanie Serrero , Jerome Filippi , Xavier Hébuterne , Nadia Arab , Virginie Cluzeau , Xavier Roblin , Emilie Del Tedesco , Laurent Beaugerie , Philippe Seksik , Anne Bourrier , Cecilia Landmann , Julien Kirchgesner , Harry Sokol , Guillaume Bouguen , Laurent Siproudhis , Marie DeWitte , Denis Franchimont , Guillaume Savoye , Anthony Buisson , Edouard Louis , Catherine Reenaers , Stephane Nancey , Gilles Boschetti , Claire Gay , Pauline Danion , Bernard Flourié , Vered Abitbol , Georgia Malamut , Jean-Marie Reimund , Benedicte Caron , Olivier DeWitt , Lucine Vuitton , Nicolas Mathieu , Sandie Pestour , Laurent Peyrin-Biroulet , Camille Zallot , Cyrielle Gilletta , Matthieu Allez , Jean-Marc Gornet , Clotilde Baudry , Stephanie Viennot , Arnaud Bourreille , Caroline Trang-Poisson , Nina Dib , Hedi Brixi , Guillaume Cadiot , Medina Boualit , Claire Painchart , Laurianne Plastaras , Romain Altwegg , Lucile Boivineau , Mathurin Fumery , Ludovic Caillo , David Laharie , Pauline Riviere , Florian Poullenot , Benoit Coffin , Henri Duboc , Stephane Nahon , Noemie Tavernier , Marion Simon , Baya Coulibaly , Morgane Amil , Duveau Nicolas , Sherine Khater , Mehdi Kaassis , Felix Goutorbe , Driffa Moussata , Laurence Picon, CHU Saint-Etienne, 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 de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Toulouse [Toulouse], CIC - Biotherapie - CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-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)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Crohn’s disease, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Cross-sectional study, [SDV]Life Sciences [q-bio], Disease, Patients experience, Inflammatory bowel disease, Tertiary care, digestive system, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Belgium, Physicians, Outpatients, medicine, Quantitative assessment, Humans, Adverse effect, Crohn's disease, Physician-Patient Relations, Hepatology, business.industry, Gastroenterology, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 3. Good health, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Family medicine, 030211 gastroenterology & hepatology, Female, France, Self Report, business
Abstract: International audience; BACKGROUND: Patients’ experience with healthcare professionals could influence their clinical outcomes. AIMS: To assess inflammatory bowel disease (IBD) patients’ experience with their disease, their treatment and their relationship with their physician. METHODS: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD. RESULTS: A quantitative assessment of the doctor-patient relationship revealed that patients’ knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample. CONCLUSION: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals.
Published: 2021

16. I-FABP is decreased in COVID-19 patients, independently of the prognosis

Author: Katell Peoc'h, Alexandre Nuzzo, Xavier Treton, Mathieu Uzzan, Kevin Guedj, E. Weiss, Olivier Corcos, Damien Soudan, Catherine Trichet, Hana Manceau, and Antonino Nicoletti
Subjects: Male, Abdominal pain, Viral Diseases, Malabsorption, Pilot Projects, 030204 cardiovascular system & hematology, medicine.disease_cause, Gastroenterology, Biochemistry, 0302 clinical medicine, Medical Conditions, Medicine and Health Sciences, Respiratory system, Coronavirus, Virus Testing, Gastrointestinal tract, Multidisciplinary, Middle Aged, Prognosis, C-Reactive Proteins, Pathophysiology, Hospitals, Intensive Care Units, Infectious Diseases, Cohort, Biomarker (medicine), Medicine, 030211 gastroenterology & hepatology, Female, lipids (amino acids, peptides, and proteins), medicine.symptom, Anatomy, Research Article, medicine.medical_specialty, Science, Pain, Fatty Acid-Binding Proteins, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Internal medicine, medicine, Humans, Aged, business.industry, SARS-CoV-2, Biology and Life Sciences, Proteins, COVID-19, Covid 19, medicine.disease, Abdominal Pain, Gastrointestinal Tract, Health Care, Health Care Facilities, Clinical Medicine, business, Digestive System, Biomarkers
Abstract: Background Severe acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) is frequently associated with gastrointestinal manifestations. Herein we evaluated the interest in measuring the intestinal fatty acid-binding protein (I-FABP), a biomarker of intestinal injury, in COVID-19 patients. Methods Serum I-FABP was analyzed in 28 consecutive patients hospitalized for a PCR-confirmed COVID-19, in 24 hospitalized patients with non-COVID-19 pulmonary diseases, and 79 patients admitted to the emergency room for abdominal pain. Results I-FABP serum concentrations were significantly lower in patients with COVID-19, as compared to patients with non-COVID-19 pulmonary diseases [70.3 pg/mL (47–167.9) vs. 161.1 pg/mL (88.98–305.2), respectively, p = 0.008]. I-FABP concentrations in these two populations were significantly lower than in patients with abdominal pain without COVID-19 [344.8 pg/mL (268.9–579.6)]. I-FABP was neither associated with severity nor the duration of symptoms. I-FABP was correlated with polymorphonuclear cell counts. Conclusions In this pilot study, we observed a low I-FABP concentration in COVID-19 patients either with or without gastrointestinal symptoms, of which the pathophysiological mechanisms and clinical impact remain to be established. Further explorations on a larger cohort of patients will be needed to unravel the molecular mechanism of such observation, including the effects of malabsorption and/or abnormal lipid metabolism.
Published: 2021

17. Effectiveness and safety of ustekinumab intensification at 90 Mg every four weeks In Crohn's disease: a multicenter study

Author: Mathurin, Fumery, Laurent, Peyrin-Biroulet, Stephane, Nancey, Romain, Altwegg, Cyrielle, Gilletta, Pauline, Veyrard, Guillaume, Bouguen, Stephanie, Viennot, Florian, Poullenot, Jerome, Filippi, Anthony, Buisson, Anne, Bozon, Franck, Brazier, Lieven, Pouillon, Bernard, Flourie, Lucile, Boivineau, Laurent, Siproudhis, David, Laharie, Xavier, Roblin, Momar, Diouf, Xavier, Treton, Jonchère, Laurent, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépatogastroentérologie [CHU Lyon-Sud], Hospices Civils de Lyon (HCL), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de Gastroentérologie et pancréatologie [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire [Rennes], Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépato-gastro-entérologie et oncologie digestive (CHU de Bordeaux), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Archet 2 [Nice] (CHU), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Gastroentérologie [CHU Bordeaux], Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux), Direction de la recherche clinique et de l'innovation [CHU Amiens], Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-CHU Saint-Eloi, Centre Hospitalier Universitaire Toulouse (CHU Toulouse), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Crohn’s disease, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, intensification, ustekinumab, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: International audience; Introduction: The approved maintenance regimens for ustekinumab in Crohn's disease (CD) are 90 mg every 8 or 12 weeks. Some patients will partially respond to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections.Methods: All patients with active CD, as defined by Harvey-Bradshaw score ≥ 4 and one objective sign of inflammation (CRP > 5 mg/L and/or fecal calprotectin > 250 µg/g and/or radiologic and/or endoscopic evidence of disease activity) who required ustekinumab dose escalation to 90mg every 4 weeks for loss of response or incomplete response to ustekinumab 90mg every 8 weeks were included in this retrospective multicenter cohort study.Results: One hundred patients, with a median age of 35 years (Interquartile Range (IQR), 28 - 49) and median disease duration of 12 (7 - 20) years were included. Dose intensification was performed after a median of 5.0 (2.8 - 9.0) months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 (1.3 - 3.0) months. After a median follow-up of 8.2 (5.6-12.4) months, 61% of patients were still treated with ustekinumab, and 26% in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission (no ulcers). At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events.Conclusion: In this multicenter study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.
Published: 2021

18. Indications de l’autogreffe de cellules hématopoïétiques dans la Maladie de Crohn : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire

Author: Ibrahim Yakoub-Agha, Zora Marjanovic, Manuela Badoglio, David Laharie, Montserrat Rovira, Xavier Treton, M. Puyade, Miguel Torregrosa Díaz Jose, Dominique Farge, Laurent Alric, Ginette Fotsing, Grégory Pugnet, Cristina Castilla Llorente, Louis Terriou, Matthieu Allez, My-Linh Tran-Minh, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Hospital Clínic de Barcelona [Catalonia, Spain], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Purpan [Toulouse], CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), CCSD, Accord Elsevier, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département d'hématologie [Gustave Roussy], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Oncology, Mobilisation des de cellules hématopoïétiques, Cancer Research, medicine.medical_specialty, Conditionnement, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Disease, Monoclonal antibody, Post autologous stem cell transplantation follow-up, Suivi post autogreffe, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Soins de support, Autologous hematopoietic cell transplantation, Internal medicine, Medicine, Radiology, Nuclear Medicine and imaging, Crohn's disease, Autogreffe de cellules hématopoïétiques, business.industry, Conditionning regimen, Hematopoietic stem cell, Hematology, General Medicine, Stem-cell therapy, medicine.disease, Supportive Care, Maladie de Crohn, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mobilization of hematopoietic cell, Immunosuppression intensive, Methotrexate, Intensive Immunosuppression, business, medicine.drug
Abstract: International audience; Crohn's Disease (CD) is an auto-inflammatory disease, which may involve the entire gastro-intestinal tract. CD is diagnosed on several clinical, biological, endoscopic and histological criteria. First line therapy is based on oral or iv steroids. In case of steroids dependence or resistance, several types of immunosuppressive or immunomodulating therapies are available: classical antimetabolites (thiopurines or methotrexate) or monoclonal antibodies against TNFα, against interleukin 12/23 or against integrin. Nonetheless, Crohn's disease may remain active despite the use of several lines of therapy. In such cases, autologous hematopoietic cell transplantation (AHCT) is an effective therapeutic option in highly selected CD patients with specific criteria. The MATHEC-SFGM-TC Good Clinical Practice Guidelines (GCPG) were developed by a multidisciplinary group of experts including gastroenterologists, hematologists and members of the reference center for stem cell therapy in auto-immune diseases (MATHEC), including members of the French groupe d'étude thérapeutique des affections inflammatoires du tube digestif(GETAID) under the auspices of the French speaking Society of bone marrow transplantation and cellular therapy (SFGM-TC). The aim of the present guidelines is to define the eligibility criteria for CD patients when candidates to AHCT, the procedures for mobilization of hematopoietic stem cell (HSC), conditioning regimen and standardized follow-up after AHCT including monitoring of gastroenterological treatments during AHCT and thereafter throughout all follow-up.
Published: 2020

19. Real-world use of therapeutic drug monitoring of CT-P13 in patients with inflammatory bowel disease: A 12-month prospective observational cohort study

Author: Pauline Jouet, Laurent Beaugerie, Anne-Laure Pelletier, Robert Benamouzig, Xavier Amiot, Nicolas Petitdidier, Georgia Malamut, Vered Abitbol, Xavier Treton, Aurelien Amiot, Lysiane Marthey, Matthieu Allez, Franck Carbonnel, Yoram Bouhnik, Sylvie Rajca, Anne Bourrier, Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Inflammatory bowel disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Trough Concentration, Prospective Studies, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Antibodies, Monoclonal, Middle Aged, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Infliximab, 3. Good health, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, Drug Monitoring, business, Cohort study, medicine.drug
Abstract: Summary Background Whether therapeutic drug monitoring (TDM) of infliximab should be implemented in daily practice is an ongoing controversy. Aims To assess the real-world use of TDM in an observational multicentre cohort study with consecutive patients with inflammatory bowel disease (IBD) treated with CT-P13. Methods Between September 2015 and December 2016, 364 patients with IBD were treated with CT-P13 in 13 gastroenterology departments and were followed up for 54 weeks. Disease activity, CT-P13 trough concentration and anti-CT-P13 antibody (ACA) were recorded. Results Steroid-free clinical remission rates at week 54 were 67.0% and 56.4% in patients with CD and UC, respectively. CT-P13 trough concentrations were measured in 70.7% of the patients. The mean CT-P13 trough concentration was 4.2 ± 4.3 μg/mL. The presence of ACA was observed in 53 (15.9%) patients. CT-P13 trough concentration was collected in a proactive approach in 62.8% of cases and in a reactive approach in 37.2%. Among patients who submitted to TDM, CT-P13 therapy was optimized in 88.7% of the reactive group and in 22.5% of the proactive group (P Conclusion In a real-world cohort of patients with IBD treated with CT-P13, more than two-thirds of the patients underwent TDM. CT-P13 optimization was much less common in the proactive approach than in the reactive approach.
Published: 2020

20. Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease

Author: Philippe Seksik, Xavier Treton, Mathurin Fumery, Claire Auzolle, Nicolas Barnich, Lionel Le Bourhis, Benjamin Pariente, Anthony Buisson, Loic Brot, Stéphane Nancey, Harry Sokol, Carmen Stefanescu, Matthieu Allez, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Clermont-Ferrand, CHU Amiens-Picardie, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, This study has been supported by grants from MSD France, Association Francois Aupetit, the Helmsley Charitable Trust and Inserm., Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AgroParisTech, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Universitaire Clermont Ferrand, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Autophagie infections immunité – Autophagy Infection Immunity, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Adult, Male, medicine.medical_specialty, Firmicutes, Disease, Gut flora, Gastroenterology, digestive system, Endoscopy, Gastrointestinal, Ileal resection, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Crohn Disease, Ileum, Recurrence, Risk Factors, Internal medicine, Proteobacteria, medicine, microbiota, Humans, Postoperative Period, Prospective Studies, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Crohn's disease, biology, business.industry, Lachnospiraceae, Healthy subjects, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, mucosa-associated, Middle Aged, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Gastrointestinal Microbiome, Cohort, 030211 gastroenterology & hepatology, Female, business, Ileal mucosa
Abstract: ObjectiveFollowing ileal resection for Crohn’s disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence.Patients and methodsIleal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France.ResultsIleal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors.ConclusionSurgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.
Published: 2020

21. Postoperative Endoscopic Recurrence on the Neoterminal Ileum But Not on the Anastomosis Is Mainly Driving Long-Term Outcomes in Crohn's Disease

Author: Madeleine Bezault, Philippe Seksik, Mathurin Fumery, Nassim Hammoudi, Benjamin Pariente, Anthony Buisson, Stéphane Nancey, Claire Auzolle, Lionel Le Bourhis, Gilles Boschetti, My-Linh Tran Minh, Xavier Treton, Matthieu Allez, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Crohn's disease, medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, Gold standard, Gastroenterology, Ileum, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Anastomosis, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Endoscopy, Surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Interquartile range, 030220 oncology & carcinogenesis, medicine, Long term outcomes, 030211 gastroenterology & hepatology, In patient, business, ComputingMilieux_MISCELLANEOUS
Abstract: Early ileocolonoscopy within the first year after surgery is the gold standard to evaluate recurrence after ileocolonic resection for Crohn's disease (CD). The aim of the study was to evaluate the association between the presence and severity of anastomotic and ileal lesions at early postoperative ileocolonoscopy and long-term outcomes. The REMIND group conducted a prospective multicenter study. Patients operated for ileal or ileocolonic CD were included. An ileocolonoscopy was performed 6 months after surgery. An endoscopic score describing separately the anastomotic and ileal lesions was built. Clinical relapse was defined by the CD-related symptoms, confirmed by imaging, endoscopy or therapeutic intensification; CD-related complications; or subsequent surgery. Among 225 included patients, long-term follow-up was available in 193 (median follow-up: 3.82 years [interquartile range: 2.56-5.41]). Median clinical recurrence-free survival was 47.6 months. Clinical recurrence-free survival was significantly shorter in patients with ileal lesions at early postoperative endoscopy whatever their severity was (I(1) or I(2,3,4)) as compared to patients without ileal lesions (I(0)) (I(0) vs I(2,3,4): P = 0.0003; I(0) vs I(1): P = 0.0008 and I(1) vs I(2,3,4): P = 0.43). Patients with exclusively ileal lesions (A(0)I(1,2,3,4)) had poorer clinical long-term outcomes than patients with exclusively anastomotic lesions (A(1,2,3)I(0)) (P = 0.009). A score describing separately the anastomotic and ileal lesions might be more appropriate to define postoperative endoscopic recurrence. Our data suggest that patients with ileal lesions, including mild ones (I(1)), could beneficiate from treatment step-up to improve long-term outcomes.
Published: 2020

22. T cell clonal expansions in ileal Crohn’s disease are associated with smoking behaviour and postoperative recurrence

Author: Benjamin Pariente, Azucena Salas, Xavier Treton, Matthieu Allez, Stéphane Nancey, Victor Chardiny, Anthony Buisson, Mathurin Fumery, Harry Sokol, Nicolas Barnich, Marjolaine Ngollo, Hugo Bottois, Carmen Stefanescu, Philippe Seksik, Ana Maria Corraliza, Claire Auzolle, Lionel Le Bourhis, Kevin Perez, Service d'hépato-gastro-entérologie, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Helmsley Charitable Trust Association Francois Aupetit MSD France laboratories, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA)
Subjects: Adult, Male, medicine.medical_specialty, Microarray, T cell, Receptors, Antigen, T-Cell, Gastroenterology, Cohort Studies, Pathogenesis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Recurrence, Internal medicine, medicine, Humans, Cytotoxic T cell, Postoperative Period, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Crohn's disease, medicine.diagnostic_test, business.industry, Smoking, T-cell receptor, Area under the curve, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Ileitis, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Endoscopy, Treatment Outcome, medicine.anatomical_structure, Female, 030211 gastroenterology & hepatology, business
Abstract: T cell clonal expansions are present in the inflamed mucosa of patients with Crohn’s disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection.MethodsT cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively.ResultsTCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment.ConclusionClonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven.Trial registration numberNCT03458195.
Published: 2019

23. Association Between Microscopic Lesions at Ileal Resection Margin and Recurrence After Surgery in Patients With Crohn’s Disease

Author: Alexandra Traverse-Glehen, Nassim Hammoudi, Olivier Corcos, Philippe Marteau, Julien Loreau, Mariane Maillet, Martine Leconte, Jonathan Catry, Yves Francois, Najim Chafai, Xavier Dray, Marjolaine Ngollo, Philippe Seksik, Pierre Cattan, Benjamin Pariente, Nicolas Munoz-Bongrand, Peggy Falgon, Stéphane Nancey, Nathan Beaupel, Isabelle Nion-Larmurier, Andrée Nisard, Christophe Attencourt, Emmanuel Tiret, Ulrika Chaput, Denis Chatelain, Marion Chauvenet, Dominique Cazals-Hatem, Eddy Cotte, Laurent Beaugerie, Madeleine Bezault, Mircea Chirica, Gilles Boschetti, Sarah Boyer, Loic Brot, Julien Kirchgesner, Hugo Bottois, Anne Dubois, Magali Svrcek, Yoram Bouhnik, Jean-Marc Gornet, Rachid Kaci, Brice Gergaud, Carmen Stefanescu, Helene Corte, Claire Auzolle, Jean-Louis Dupas, Juliette Joubert Zakeyh, Leila Chedouba, Amine Rahili, Elodie Quévrain, Charles Sabbagh, Lionel Le Bourhis, Maria Nachury, Anne Bourrier, Nathalie Guedj, Florence Renaud, Helena Hadjisavvas, Charlotte Gardair, Gilles Bommelaer, Céline Grand, Xavier Treton, Xavier Jouven, Anthony Buisson, Jérémie H. Lefevre, Paul Hofmann, Stéphanie Patouraux, Jérôme Filippi, Xavier Hébuterne, Driffa Moussata, Clotilde Baudry, Nelson Lourenco, Marion Goutte, Harry Sokol, Victor Chardiny, My-Linh Tran-Minh, Bernard Flourié, Pierre Desreumaux, Catherine Godfraind, Coralie Sommeville, Mathurin Fumery, Nicolas Barnich, Joëlle Bonnet, Anne-Laure Charlois, Dilek Coban, Leon Magiorri, Yves Panis, Matthieu Allez, Jean-François Fléjou, Franck Brazier, M. Ferron, Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Département de Pathologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Hôpital Beaujon [AP-HP], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Cryptitis, Ileum, REMIND Trial, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Recurrence, Interquartile range, medicine, Humans, Prospective Studies, Colectomy, Digestive System Surgical Procedures, Outcome, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Prognostic Factor, IBD Surgery, Anastomosis, Surgical, Gastroenterology, Margins of Excision, Histology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Odds ratio, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Endoscopy, Surgery, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Complication, business
Abstract: International audience; Background and AimsDifferent types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn’s disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence.MethodsWe collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery.ResultsSix months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026).ConclusionIn patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.
Published: 2019

24. Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics – Lung axis hypothesis

Author: Jerome Martin, Yoram Bouhnik, Mathieu Uzzan, Olivier Corcos, Xavier Treton, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d’Immunologie, Centre d’Immunomonitorage Nantes Atlantique (CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), and Le Bihan, Sylvie
Subjects: 0301 basic medicine, Male, ARDS, Intra-Abdominal Fat, Critical Care, [SDV]Life Sciences [q-bio], Inflammation, Systemic inflammation, Article, Permeability, Lymphatic System, 03 medical and health sciences, 0302 clinical medicine, Immune system, Ischemia, Risk Factors, medicine, Humans, Obesity, Lung, Metabolic Syndrome, Intestinal permeability, business.industry, fungi, COVID-19, General Medicine, Models, Theoretical, Overweight, medicine.disease, Systemic Inflammatory Response Syndrome, 3. Good health, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Systemic inflammatory response syndrome, Intensive Care Units, 030104 developmental biology, medicine.anatomical_structure, Immune System, Immunology, Cytokines, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; Consistent observations report increased severity of SARS-CoV-2 infection in overweight men with cardiovascular factors. As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. SARS-CoV2 presents the ability to infect epithelial cells of the respiratory tract as well as the intestinal tract. Several factors may increase intestinal permeability including direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2- associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPs (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). The pro-inflammatory cytokines produced by the mesentery fat mediates systemic inflammation and aggravate acute respiratory distress syndrome (ARDS) through the mesenteric lymph drainage.
Published: 2020

25. Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A

Author: Anne Couvelard, Eric Ogier-Denis, Valérie Gratio, G. LeGuilloux, Neïké Fernandez, Isabelle Chantret, C. Prochasson, Thierry Voisin, Alain Couvineau, Anne Jarry, Xavier Treton, N. Messal, Pascal Nicole, Stéphanie Dayot, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Biomarqueurs prédictifs de la progression des metaplasies et dysplasies des epitheliums (Biométadys), Université de Nantes (UN), Bernardo, Elizabeth, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Male, 0301 basic medicine, Colorectal cancer, T-Lymphocytes, Inflammatory bowel disease, Ectopic Gene Expression, Mice, GPCR, Orexin Receptors, Intestinal Mucosa, Mice, Knockout, Mice, Inbred BALB C, Dextran Sulfate, digestive, oral, and skin physiology, NF-kappa B, Middle Aged, Ulcerative colitis, 3. Good health, Knockout mouse, Cytokines, Molecular Medicine, Female, Orexin Receptor Antagonists, medicine.symptom, psychological phenomena and processes, Signal Transduction, Adult, Down-Regulation, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Line, Young Adult, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, mental disorders, medicine, Animals, Humans, Colitis, Molecular Biology, Retrospective Studies, Orexins, business.industry, Phenylurea Compounds, Epithelial Cells, medicine.disease, digestive system diseases, Mice, Inbred C57BL, Disease Models, Animal, Neuropeptide, 030104 developmental biology, nervous system, Cancer research, Colitis, Ulcerative, Ectopic expression, business
Abstract: International audience; Orexins (orexin-A and orexin-B) are hypothalamic peptides that are produced by the same precursor and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long-lasting inflammation and ulcers that affect the colon and rectum mucosa and is known to be a significant risk factor for colon cancer development. Based on our recent studies showing that OX1R is aberrantly expressed in colon cancer, we wondered whether orexin-A could play a role in UC. Immunohistochemistry studies revealed that OX1R is highly expressed in the affected colonic epithelium of most UC patients, but not in the non-affected colonic mucosa. Injection of exogenous orexin-A specifically improved the inflammatory symptoms in the two colitis murine models. Conversely, injection of inactive orexin-A analog, OxB7-28 or OX1R specific antagonist SB-408124 did not have anti-inflammatory effect. Moreover, treatment with orexin-A in DSS-colitis induced OX1R −/− knockout mice did not have any protective effect. The orexin-A anti-inflammatory effect was due to the decreased expression of pro-inflammatory cytokines in immune cells and specifically in T-cells isolated from colonic mucosa. Moreover, orexin-A inhibited canonical NFκB activation in an immune cell line and in intestinal epithelial cell line. These results suggest that orexin-A might represent a promising alternative to current UC therapies.
Published: 2018

26. Male gender, active smoking and previous intestinal resection are risk factors for post-operative endoscopic recurrence in Crohn's disease: results from a prospective cohort study

Author: Xavier Treton, Mathurin Fumery, Claire Auzolle, Xavier Jouven, Benjamin Pariente, Philippe Marteau, Nassim Hammoudi, Carmen Stefanescu, Philippe Seksik, Anthony Buisson, My-Linh Tran-Minh, Matthieu Allez, Stéphane Nancey, INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Service d'hépato-gastroentérologie, Hospices Civils de Lyon (HCL), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pole des maladies de l'appareil digestif, gastroentérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), AP-HP Hôpital Beaujon, CHU Saint-Antoine [APHP], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Multivariate analysis, Disease, Anastomosis, Lower risk, 03 medical and health sciences, 0302 clinical medicine, medicine, Pharmacology (medical), Prospective cohort study, Male gender, ComputingMilieux_MISCELLANEOUS, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Surgery, Endoscopy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business
Abstract: BACKGROUND After ileocaecal resection for Crohn's disease (CD), inflammatory lesions frequently recur on the anastomosis and/or on the neo-terminal ileum. AIM To identify predictors of early post-operative endoscopic recurrence. METHODS From September 2010 to September 2017, the REMIND group conducted a prospective nationwide study in nine French academic centres. Data were collected at the time of surgery and endoscopy, performed 6-12 months after surgery. Endoscopic recurrence was defined as a Rutgeerts score ≥i2. Baseline factors associated with endoscopic recurrence were searched by univariate and multivariate regression analysis. RESULTS Two hundred and eighty-nine CD patients were included. Endoscopy within 1 year following surgery was performed in 225 (78%) patients (104M/121F). Mean age and disease duration were 35 (12.2) and 8.8 (8.9) years respectively. Seventy (32%) patients were active smokers at surgery. One hundred and forty-two (63%) patients received at least one anti-TNF therapy before surgery. After surgery, 40 (18%) patients received thiopurines and 66 (29%) received an anti-TNF agent. Endoscopic recurrence occurred in 107 (47%) patients. In multivariate analysis, male gender (OR = 2.48 [IC 95% 1.40-4.46]), active smoking at surgery (OR = 2.65 [IC 95% 1.44-4.97]) and previous resection (OR = 3.03 [IC 95% 1.36-7.12]) were associated with a higher risk of endoscopic recurrence. Inversely, post-operative anti-TNF treatment decreased the risk of endoscopic recurrence (OR = 0.50 [IC 95% 0.25-0.96]). CONCLUSIONS Male gender, active smoking at surgery and previous intestinal resection are associated with a higher risk of endoscopic post-operative recurrence, while post-operative anti-TNF treatment is associated with a lower risk.
Published: 2018

27. Effectiveness and safety of anti-TNF therapy for inflammatory bowel disease in liver transplant recipients for primary sclerosing cholangitis: A nationwide case series

Author: David Laharie, Sébastien Dharancy, Maria Nachury, Sylvie Radenne, Laurent Peyrin-Biroulet, Vincent Leroy, Roman Combes, Christophe Duvoux, François Durand, Filomena Conti, Georges-Philippe Pageaux, Jérôme Dumortier, Lucile Boivineau, Xavier Treton, Romain Altwegg, Felix Goutorbe, Victor de Ledinghen, Olivier Chazouillères, Géraldine Lamblin, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Université de Montpellier (UM)-CHU Saint-Eloi, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'hépatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Edouard Herriot [CHU - HCL], Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, CHU Clermont-Ferrand, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: Male, Colorectal cancer, Cholangitis, medicine.medical_treatment, Anti-TNF alpha, [SDV]Life Sciences [q-bio], 030230 surgery, Liver transplantation, Gastroenterology, Inflammatory bowel disease, Sclerosing, 0302 clinical medicine, Adrenal Cortex Hormones, Medicine, Remission Induction, Colonoscopy, Middle Aged, Ulcerative colitis, 3. Good health, Combination, Disease Progression, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, Colorectal Neoplasms, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Cholangitis, Sclerosing, Tacrolimus, Primary sclerosing cholangitis, 03 medical and health sciences, Young Adult, Drug Therapy, Internal medicine, Adalimumab, Humans, Retrospective Studies, Hepatology, business.industry, Tumor Necrosis Factor-alpha, medicine.disease, Inflammatory Bowel Diseases, Infliximab, digestive system diseases, Liver Transplantation, business
Abstract: International audience; BACKGROUND: There is a lack of consensus regarding the treatment of inflammatory bowel disease (IBD) after liver transplantation (LT) forprimary sclerosing cholangitis (PSC). AIM: To investigate the safety and effectiveness of anti-TNF therapy in patients with IBD after a LT for PSC. METHODS: We reviewed the medical files of all of the IBD patients who underwent a LT for PSC and who were treated with anti-TNF therapy at 23 French liver transplantation centers between 1989 and 2012. RESULTS: Eighteen patients (12 with ulcerative colitis and 6 who had Crohn's disease) were recruited at 9 LT centers. All of these patients received infliximab or adalimumab following their LT, and the median duration of their anti-TNF treatment was 10.4 months. The most frequent concomitant immunosuppressive treatment comprised a combination of tacrolimus and corticosteroids. Following anti-TNF therapy induction, a clinical response was seen in 16/18 patients (89%) and clinical remission in 10 (56%). At the end of the anti-TNF treatment or at the last follow-up examination (the median follow-up was 20.9 months), a clinical response was achieved in 12 patients (67%) and clinical remission in 7 (39%). A significant endoscopic improvement was observed in 9 out of 14 patients and a complete mucosal healing in 3 out of 14 patients (21%). Six patients experienced a severe infection. These were due to cholangitis, cytomegalovirus (CMV) infection, Clostridium difficile, cryptosporidiosis, or Enterococcus faecalis. Three patients developed colorectal cancer after LT, and two patients died during the follow-up period. CONCLUSIONS: Anti-TNF therapy proved to be effective for treating IBD after LT for PSC. However, as 17% of the patients developed colorectal cancer during the follow-up, colonoscopic annual surveillance is recommended after LT, as specified in the current guidelines.
Published: 2018

28. Risk of Rectal Neoplasia after Colectomy and Ileorectal Anastomosis for Ulcerative Colitis

Author: Xavier Treton, Anne-Laure Pelletier, Nadia Oubaya, Antoine Brouquet, Philippe Seksik, Vered Abitbol, Nicola de’ Angelis, Mathieu Uzzan, Mathurin Fumery, Anthony Buisson, Stéphane Nancey, Romain Altwegg, Julien Kirchgesner, Gilles Boschetti, Yves Panis, Maria Nachury, David Laharie, Jean-Marc Gornet, Aurelien Amiot, Jacques Cosnes, Matthieu Allez, Eddy Cotte, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], EA 4393 EC2M3 Laboratoire d'Investigation Clinique, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie oncologique, Hospices Civils de Lyon (HCL), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Département de Gastroentérologie, Hôpital Européen [Fondation Ambroise Paré - Marseille], Hôpital Bichat - Claude Bernard, Département de gastroentérologie, CHU Cochin [AP-HP], Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), CHU Amiens-Picardie, Service de Chirurgie générale et digestive [CHU Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Hépato-gastro-entérologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Anastomosis, Gastroenterology, Inflammatory bowel disease, Primary sclerosing cholangitis, Young Adult, 03 medical and health sciences, Ileostomy, 0302 clinical medicine, Ileum, Risk Factors, Internal medicine, medicine, Carcinoma, Humans, Colectomy, ComputingMilieux_MISCELLANEOUS, Proportional Hazards Models, Retrospective Studies, Management of ulcerative colitis, Rectal Neoplasms, business.industry, Anastomosis, Surgical, Rectum, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, Middle Aged, medicine.disease, Ulcerative colitis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030220 oncology & carcinogenesis, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, business
Abstract: Background and aims Colectomy can be required in the management of ulcerative colitis [UC]. While ileal-pouch anal anastomosis [IPAA] is the recommended reconstruction technique, ileorectal anastomosis [IRA] is still performed and might present some advantages. However, the risk of rectal neoplasia might limit its indication. The aims of our study were to determine the incidence of rectal neoplasias following IRA for UC and to identify risk factors associated with rectal carcinomas. Methods We performed a multicenter retrospective study including patients who underwent IRA for UC from 1960 to 2014 in 13 centers. Cox-proportional hazard models were used to determine carcinoma-associated risk factors. Results A total of 343 patients were included, with a median follow-up of 10.4 years after IRA. At the end of follow-up, 38 rectal neoplasias (including 19 carcinomas) were diagnosed, and 7 patients [2%] had either died from rectal carcinoma or had a metastatic disease. Incidences of rectal carcinoma after IRA for UC were estimated at 3.2% at 10 years and at 7.3% at 20 years, whereas incidences of neoplasia were estimated at 7.1% and 14% at 10 and 20 years, respectively. In multivariate analysis, age at IRA, IBD duration, primary sclerosing cholangitis [PSC] and history of prior colonic carcinoma were independently associated with the risk of rectal carcinoma following IRA. Conclusion The risk of rectal carcinoma in patients with IRA for UC remains, and this justifies long-term endoscopic surveillance. Either IPAA or end ileostomy should be considered in 'high-risk' patients i.e. those with PSC and/or with prior colonic neoplasia.
Published: 2017

29. Topological Modelling of Deep Ulcerations in Patients with Ulcerative Colitis

Author: Gilles Wainrib, Eric Ogier-Denis, Ian Morilla, Hatem Zaag, Xavier Treton, Mathieu Uzzan, Dominique Cazals-Hatem, Service d'Anatomo-Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Xavier Bichat, Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: 0301 basic medicine, business.industry, Inference, medicine.disease, Topology, Inflammatory bowel disease, Ulcerative colitis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], digestive system diseases, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Cohort, Medicine, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], In patient, business, ComputingMilieux_MISCELLANEOUS
Abstract: Aims: Steadily the clinicians of our team in inflammatory bowel disease encounter ulcerative colitis patients that develop deep ulcers during their treatment. Currently, these practitioners are only equipped with their grade of expertise in inflammatory domains to decide what new therapy maybe use in such cases. Encouraged by the limited knowledge of this frequent pathology, we seek to determine the molecular conditions underlying the recurrent formation of deep ulcerations in certain group of patients. Method: The goal of this strategy is to expose differences between groups of patients based on similarities computed by random walk graph kernels and performing functional inference on those differences. Results: We apply the methodology to a cohort of eleven miRNA microarrays of ulcerative colitis patients. Our results showed how the group of ulcerative colitis patients with presence of deep ulcers is topologically more similar (0.35) than ulcerative colitis patients (0.18) to control. Such topological constraint drove functional inference to complete the information that clinicians need. Conclusions: Our analyses reveal highly interpretable in the guidance of practitioners to eventually correct initial therapies of ulcerative colitis patients that develop deep ulcers. The methodology can provide them with useful molecular hypotheses necessaries prior to make any decision on the newest course of the treatment.
Published: 2017

30. MicroRNA-based diagnostic tools for advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C

Author: Kevin Appourchaux, Safi Dokmak, Matthieu Resche-Rigon, Xavier Treton, Martine Lapalus, Charles-Henry Gattolliat, Emmanuelle Porchet, Michelle Martinot-Peignoux, Nathalie Boyer, Michel Vidaud, Pierre Bedossa, Patrick Marcellin, Ivan Bièche, Emilie Estrabaud, and Tarik Asselah
Published: 2016
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31. Integrative Network-based Analysis of Colonic Detoxification Gene Expression in Ulcerative Colitis According to Smoking Status

Author: Yannick Ladeiro, Yong-Ping Ding, Ian Morilla, Assiya Marah, Xavier Treton, Dominique Cazals-Hatem, Gilles Wainrib, Fanny Daniel, Philippe Seksik, Eric Ogier-Denis, Yoram Bouhnik, Hatem Zaag, Jean-Pierre Hugot, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie de la réactivite bronchique et vasculaire, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Service d'Anatomo-Pathologie, Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Recherche pour le Développement, UR 178 Fundamentals & Domains of Disease Emergence (IRD UR178), Faculté de Médecine Xavier Bichat, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, 0301 basic medicine, Colon, Gene Expression, Disease, Real-Time Polymerase Chain Reaction, Inflammatory bowel disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Gene interaction, Detoxification, Gene expression, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Principal Component Analysis, business.industry, Smoking, Gastroenterology, General Medicine, Middle Aged, medicine.disease, Ulcerative colitis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, 030104 developmental biology, Real-time polymerase chain reaction, Case-Control Studies, Inactivation, Metabolic, Immunology, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, business, Homeostasis
Abstract: Backgrounds and Aims: The effect of cigarette smoking [CS] is ambivalent since smoking improves ulcerative colitis [UC] while it worsens Crohn’s disease [CD]. Although this clinical relationship between inflammatory bowel disease [IBD] and tobacco is well established, only a few experimental works have investigated the effect of smoking on the colonic barrier homeostasis focusing on xenobiotic detoxification genes. Methods: A comprehensive and integrated comparative analysis of the global xenobiotic detoxification capacity of the normal colonic mucosa of healthy smokers [ n = 8] and non-smokers [ n = 9] versus the non-affected colonic mucosa of UC patients [ n = 19] was performed by quantitative real-time polymerase chain reaction [qRT PCR]. The detoxification gene expression profile was analysed in CD patients [ n = 18], in smoking UC patients [ n = 5], and in biopsies from non-smoking UC patients cultured or not with cigarette smoke extract [ n = 8]. Results: Of the 244 detoxification genes investigated, 65 were dysregulated in UC patients in comparison with healthy controls or CD patients. The expression of ≥ 45/65 genes was inversed by CS in biopsies of smoking UC patients in remission and in colonic explants of UC patients exposed to cigarette smoke extract. We devised a network-based data analysis approach for differentially assessing changes in genetic interactions, allowing identification of unexpected regulatory detoxification genes that may play a major role in the beneficial effect of smoking on UC. Conclusions: Non-inflamed colonic mucosa in UC is characterised by a specifically altered detoxification gene network, which is partially restored by tobacco. These mucosal signatures could be useful for developing new therapeutic strategies and biomarkers of drug response in UC.
Published: 2016

32. Increased Proliferation of the Ileal Epithelium as a Remote Effect of Ulcerative Colitis

Author: Eric Ogier-Denis, Dominique Cazals-Hatem, Fanny Daniel, Frédérick Barreau, Eric Pedruzzi, Nicolas Montcuquet, Shirin Sedghi, Xavier Treton, Jean-Pierre Hugot, Ian Morilla, Emilie Rannou, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Association Francois Aupetit, AFAInstitut National de la SantÃ© et de la Recherche MÃ©dicale, InsermCentre National de la Recherche Scientifique, CNRS
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, MAP Kinase Signaling System, [SDV]Life Sciences [q-bio], Inflammation, Biology, Inflammatory bowel disease, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Ileum, medicine, Animals, Humans, Immunology and Allergy, Intestinal Mucosa, Colitis, Wnt Signaling Pathway, beta Catenin, Cell Proliferation, Gastroenterology, Wnt signaling pathway, medicine.disease, Ulcerative colitis, Small intestine, 3. Good health, Mice, Inbred C57BL, Interleukin 10, 030104 developmental biology, medicine.anatomical_structure, Trinitrobenzenesulfonic Acid, Case-Control Studies, 030220 oncology & carcinogenesis, Immunology, Colitis, Ulcerative, medicine.symptom
Abstract: Background Aside from cases of backwash ileitis, the ileal mucosa of patients with ulcerative colitis (UC), an idiotypic inflammatory bowel disease, has received little attention despite the fact that colitis is known to trigger alterations in morphology and/or functions of the small intestine remotely. Methods The ileal mucosa was studied in patients with UC and in a spontaneous model of colitis (Il10/Nox1 dKO mice) mimicking the histological and clinical features of UC and was also studied in acute and chronic murine models of chemically induced colitis. Proliferation and apoptosis were assessed using morphological and immunohistological methods and Western blot analysis. Peyer's patch immune cell subsets were analyzed. Cytokines levels were quantified using quantitative PCR and Luminex xMAP technology. Total RNA from isolated ileal crypts was used for whole genome transcriptome analysis. Results The most striking features were an increased ileal crypt length associated with an enhanced cell proliferation of the transit-amplifying cells along with activation of the Wnt/β-catenin and MAPkinase pathways. These changes did not result from intestinal inflammation as assessed by histology and/or pro-inflammatory cytokine expression levels. The increased proliferation rate was dependent on the duration but not on the severity of colitis and was observed in different mouse models of colitis, including the Il10/Nox1 dKO model and 2,4,6-trinitrobenzenesulfonic acid-treated mice. Interestingly, the ileal mucosa of patients with UC also displayed longer crypts and enhanced cell proliferation compared with control patients. Conclusions These data show that despite the absence of inflammation in the small intestine, alterations in the ileal mucosa homeostasis are present in UC. Copyright © 2016 Crohn's and Colitis Foundation of America, Inc.
Published: 2016

33. Effect of appendicectomy on colonic inflammation and neoplasia in experimental ulcerative colitis

Author: Eric Ogier-Denis, Léon Maggiori, Xavier Treton, Karim Boudjema, Yves Panis, Yann Harnoy, Yoram Bouhnik, Dominique Cazals-Hatem, Laurent Sulpice, Nathalie Gault, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), LabEx Inflamex, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Hôpital Beaujon, AP HP, Departement de Gastroenterologie et d'assistance Nutritive, Université Paris Diderot - Paris 7 (UPD7), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], Association Francois Aupetit, Societe Francaise de Chirurgie Digestive, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Beaujon, Service de Chirurgie Hépatobiliaire et Digestive, and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: Adult, Male, medicine.medical_specialty, appendicitis, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Laparotomy, Medicine, Animals, Appendectomy, Humans, Colitis, Colectomy, business.industry, Rectal Neoplasms, colorectal-cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, suppression, medicine.disease, Ulcerative colitis, Appendix, Appendicitis, 3. Good health, Interleukin-10, Mice, Inbred C57BL, medicine.anatomical_structure, Dysplasia, 030220 oncology & carcinogenesis, Chronic Disease, Colonic Neoplasms, 030211 gastroenterology & hepatology, Surgery, Colitis, Ulcerative, Female, protects, business, bowel-disease
Abstract: International audience; BackgroundUlcerative colitis (UC) promotes cancer, and can be ameliorated by early appendicectomy for appendicitis. The aim of the study was to explore the effect of appendicectomy on colitis and colonic neoplasia in an animal model of colitis and a cohort of patients with UC. MethodsFive-week old IL10/Nox1(DKO) mice with nascent colitis and 8-week-old IL10/Nox1(DKO) mice with established colitis underwent appendicectomy (for experimental appendicitis or no appendicitis) or sham laparotomy. The severity and extent of colitis was assessed by histopathological examination, and a clinical disease activity score was given. From a cohort of consecutive patients with UC who underwent colectomy, the prevalence of appendicectomy and pathological findings were collected from two institutional databases. ResultsAppendicectomy for appendicitis ameliorated experimental colitis in the mice; the effect was more pronounced in the 5-week-old animals. Appendicectomy in the no-appendicitis group was associated with an increased rate of colonic high-grade dysplasia (HGD) or cancer compared with rates in sham and appendicitis groups (13 of 20 versus 0 of 20 and 0 of 20 respectively; P < 0001). Fifteen of 232 patients who underwent colectomy for UC had previously had an appendicectomy, and nine of these had colonic cancer or HGD. Thirty (138 per cent) of 217 patients with the appendix insitu had colonic neoplastic lesions. Multivariable analysis showed that previous appendicectomy was associated with colorectal neoplasia (odds ratio 1688, 95 per cent c.i. 332 to 11269). ConclusionAppendicectomy for experimental appendicitis ameliorated colitis. The risk of colorectal neoplasia appeared to increase following appendicectomy without induced appendicitis in a mouse model of colitis, and in patients with UC who had undergone appendicectomy. Surgical relevance Appendicectomy for appendicitis protects against UC. In this murine model of colitis, appendicectomy for experimental appendicitis protected against colitis, but appendicectomy without appendicitis promoted colorectal carcinogenesis. In patients with ulcerative colitis who underwent colectomy, absence of the appendix (proof of previous appendicectomy) in the resection specimen was independently associated with colorectal neoplasia. Although patients with UC and a history of appendicectomy represent a small subset, they may need closer monitoring for colorectal neoplasia. Appendicectomy reduces inflammation, increases risk for cancer
Published: 2016

34. Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery

Author: Marion Leclerc, Yoram Bouhnik, Joël Doré, Matthieu Allez, P Pochart, Philippe Marteau, J-F Colombel, P. Seksik, Patricia Lepage, Stanislas Mondot, Xavier Treton, MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Institut Curie, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Alloimmunité-Autoimmunité-Transplantation ( A2T ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Icahn School of Medicine at Mount Sinai [New York], Laboratoire de Biologie, Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Université Paris Descartes - Paris 5 ( UPD5 ), Service de Gastroentérologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Pierre et Marie Curie - Paris 6 (UPMC), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Université Paris Descartes - Paris 5 (UPD5), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Institut Curie [Paris], Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), and HAL-UPMC, Gestionnaire
Subjects: 0301 basic medicine, medicine.medical_specialty, Colon, Biopsy, IBD, Faecalibacterium prausnitzii, Biology, Inflammatory bowel disease, 03 medical and health sciences, Intestinal mucosa, Crohn Disease, Double-Blind Method, Ruminococcus gnavus, INFLAMMATORY BOWEL DISEASES, Ileum, Recurrence, medicine, Humans, COHORT, Intestinal Mucosa, Lactobacillus johnsonii, Crohn's disease, Lachnospiraceae, Remission Induction, Gastroenterology, RIBOSOMAL-RNA, COLITIS, RECURRENCE, BACTERIA, PATHWAYS, HEALTH, TRACT, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, biology.organism_classification, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, Gastrointestinal Microbiome, 030104 developmental biology, Immunology, Dysbiosis, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Follow-Up Studies
Abstract: the GETAID : Groupe d'Etude des Traitements des Affections Inflammatoires Digestives, Paris, France; International audience; Objectives: Preventing postoperative recurrence after ileocolonic resection (ICR) for Crohn's disease (CD) is challenging. Defining the disturbances of the microbial composition and community structure after ICR and their link with early disease recurrence is crucial.Design: Microbiota composition (fingerprinting and 16S rDNA sequencing) and community structure (correlation networks of bacterial species) were assessed from ileal mucosa sampled in 20 patients undergoing ICR and 6 months later during endoscopy from above (neoterminal ileum) and below (subanastomotic colon) the surgical anastomosis.Results: ICR had a dramatic effect on gut microbial ecosystem. At surgery, CD mucosa harboured a dysbiotic microbiota with high proportions of α/β Proteobacteria and Bacilli. Six months later, half of the patients had recurrent lesions at ileocolonoscopy and presented higher numbers of Lachnospiraceae. Recurrence of endoscopic lesions was associated with enrichment in Enterococcus durans while patients in remission had increased proportions of Dorea longicatena and Bacteroides plebeius. Structural differences were striking between recurrence and remission microbiota; while the microbiota of patients with CD recurrence exhibited a loose community structure, the microbiota of patients in remission displayed communities that were robustly correlated to each other. Microbiota colonising the neoterminal ileum and subanastomotic colon 6 months after ICR only differed in patients with recurrence.Conclusions: ICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern.
Published: 2016

35. Long-Term Outcome of Enterocutaneous Fistula in Patients With Crohn's Disease Treated With Anti-TNF Therapy: A Cohort Study from the GETAID

Author: Vida Setakhr, Vered Abitbol, Xavier Treton, Yoram Bouhnik, Aurelien Amiot, Michel Veyrac, Jean Marie Reimund, Mathieu Allez, Marc Lémann, Philippe Seksik, Jacques Moreau, Jacques Cosnes, Martine De Vos, David Laharie, Bernard Flourié, Jean-Frederic Colombel, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de gastro-entérologie et assistance nutritive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service d'Hépato-gastroentérologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service des Maladies Infectieuses et Tropicales [CHU Hôpital Nord - Marseille] (M.I.T), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Fédération Médico-Chirurgicale des Maladies de l'Appareil Digestif, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Hepato-Gastroenterology, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Pole des maladies de l'appareil digestif, gastroentérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and AP-HP Hôpital Beaujon
Subjects: Male, Enterocutaneous fistula, Time Factors, Cutaneous Fistula, Gastroenterology, Colonic Diseases, 0302 clinical medicine, Crohn Disease, Colon surgery, Intestine, Small, Young adult, Crohn's disease, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Anastomosis, Surgical, Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Monoclonal, Middle Aged, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Colon, Antibodies, Monoclonal, Humanized, Young Adult, 03 medical and health sciences, Ileum, Internal medicine, Intestinal Fistula, medicine, Adalimumab, Humans, Duodenal Diseases, Retrospective Studies, Hepatology, Tumor Necrosis Factor-alpha, business.industry, Retrospective cohort study, medicine.disease, Infliximab, digestive system diseases, Surgery, business, Follow-Up Studies
Abstract: International audience; : OBJECTIVES:Although anti-tumor necrosis factor (TNF) therapy is the treatment of choice for perianal fistulizing Crohn's disease (CD), the efficacy and safety of anti-TNF therapy in enterocutaneous fistula (ECF) remains unclear.METHODS:Between January 2008 and December 2009, we retrospectively reviewed the outcomes of all CD patients with ECF (excluding perianal fistula) treated with anti-TNF therapy followed up in Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) centers. ECF closure and tolerance of anti-TNF therapy were studied using univariate and multivariate analyses.RESULTS:Forty-eight patients (twenty-six women; median age 34.6 (interquartile range=25.0-45.5) years) were included in this study. The median follow-up period was 3.0 (2.0-6.6) years. The fistula was located in the small bowel (n=38), duodenum (n=1), and colon (n=9). The fistula has been developed in ileocolonic anastomosis in 17 (35%) cases. Sixteen patients (33%) had complex fistulas with multiple tracts and eleven patients (23%) had a high ECF output (if wearing an ostomy bag). Complete ECF closure was achieved in 16 (33%) patients, of whom eight relapsed during the follow-up period. In multivariate analysis, complete ECF closure was associated with the absence of multiple ECF tracts and associated stenosis. An abdominal abscess developed in 15 (31%) patients. ECF resection was needed in 26 (54%) patients. One patient died after surgery owing to abdominal sepsis.CONCLUSIONS:In CD patients with ECF, anti-TNF therapy may be effective in up to one-third of patients, especially in the absence of stenosis and complex fistula. A careful selection of patients is mandatory to prevent treatment failure and improves the safety.Am J Gastroenterol advance online publication, 5 August 2014; doi:10.1038/ajg.2014.183.
Published: 2014

36. Prevalence of Yersinia Species in the Ileum of Crohn's Disease Patients and Controls

Author: Guillaume Le Baut, Claire O'Brien, Paul Pavli, Maryline Roy, Philippe Seksik, Xavier Tréton, Stéphane Nancey, Nicolas Barnich, Madeleine Bezault, Claire Auzolle, Dominique Cazals-Hatem, Jérome Viala, Matthieu Allez, The REMIND GROUP, Jean-Pierre Hugot, and Anne Dumay
Subjects: yersinia, Crohn's disease, gut microbiota, ileal mucosa, innate immunity, mucosal immune system, Microbiology, QR1-502
Abstract: Yersinia are common contaminants of food products, but their prevalence in the human gut is poorly documented. Yersinia have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gyrB gene of Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and the inv gene of Y. pseudotuberculosis. We analyzed a total of 470 ileal samples taken from 338 participants (262 CD patients and 76 controls) belonging to three independent cohorts. All patients and controls were phenotyped and genotyped for the main CD susceptibility variants: NOD2, ATG16L1, and IRGM. Yersinia were found in 7.7% of ileal samples (respectively 7.9 and 7.6% in controls and CD patients) corresponding to 10% of participants (respectively 11.8 and 9.5% in controls and CD patients). Y. enterocolitica, Y. pseudotuberculosis and Y. intermedia were the most frequently identified species. The bacteria were more frequent in resected specimens, lymph nodes and Peyer's patches. Yersinia were no more likely to be detected in CD tissues than tissues from inflammatory and non-inflammatory controls. CD patients treated with immunosuppressants were less likely to be Yersinia carriers. In conclusion, this work shows that Yersinia species are frequently found at low levels in the human ileum in health and disease. The role of Yersinia species in this ecosystem should now be explored.
Published: 2018
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37. Combined NADPH oxidase 1 and interleukin 10 deficiency induces chronic endoplasmic reticulum stress and causes ulcerative colitis-like disease in mice.

Author: Xavier Tréton, Eric Pedruzzi, Cécile Guichard, Yannick Ladeiro, Shirin Sedghi, Mélissa Vallée, Neike Fernandez, Emilie Bruyère, Paul-Louis Woerther, Robert Ducroc, Nicolas Montcuquet, Jean-Noel Freund, Isabelle Van Seuningen, Frédérick Barreau, Assiya Marah, Jean-Pierre Hugot, Dominique Cazals-Hatem, Yoram Bouhnik, Fanny Daniel, and Eric Ogier-Denis
Subjects: Medicine, Science
Abstract: Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the rectum which progressively extents. Its etiology remains unknown and the number of treatments available is limited. Studies of UC patients have identified an unbalanced endoplasmic reticulum (ER) stress in the non-inflamed colonic mucosa. Animal models with impaired ER stress are sensitive to intestinal inflammation, suggesting that an unbalanced ER stress could cause inflammation. However, there are no ER stress-regulating strategies proposed in the management of UC partly because of the lack of relevant preclinical model mimicking the disease. Here we generated the IL10/Nox1dKO mouse model which combines immune dysfunction (IL-10 deficiency) and abnormal epithelium (NADPH oxidase 1 (Nox1) deficiency) and spontaneously develops a UC-like phenotype with similar complications (colorectal cancer) than UC. Our data identified an unanticipated combined role of IL10 and Nox1 in the fine-tuning of ER stress responses in goblet cells. As in humans, the ER stress was unbalanced in mice with decreased eIF2α phosphorylation preceding inflammation. In IL10/Nox1dKO mice, salubrinal preserved eIF2α phosphorylation through inhibition of the regulatory subunit of the protein phosphatase 1 PP1R15A/GADD34 and prevented colitis. Thus, this new experimental model highlighted the central role of epithelial ER stress abnormalities in the development of colitis and defined the defective eIF2α pathway as a key pathophysiological target for UC. Therefore, specific regulators able to restore the defective eIF2α pathway could lead to the molecular remission needed to treat UC.
Published: 2014
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38. Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease.

Author: Magali Fasseu, Xavier Tréton, Cécile Guichard, Eric Pedruzzi, Dominique Cazals-Hatem, Christophe Richard, Thomas Aparicio, Fanny Daniel, Jean-Claude Soulé, Richard Moreau, Yoram Bouhnik, Marc Laburthe, André Groyer, and Eric Ogier-Denis
Subjects: Medicine, Science
Abstract: BACKGROUND: Ulcerative Colitis (UC) and Crohn's Disease (CD) are two chronic Inflammatory Bowel Diseases (IBD) affecting the intestinal mucosa. Current understanding of IBD pathogenesis points out the interplay of genetic events and environmental cues in the dysregulated immune response. We hypothesized that dysregulated microRNA (miRNA) expression may contribute to IBD pathogenesis. miRNAs are small, non-coding RNAs which prevent protein synthesis through translational suppression or mRNAs degradation, and regulate several physiological processes. METHODOLOGY/FINDINGS: Expression of mature miRNAs was studied by Q-PCR in inactive colonic mucosa of patients with UC (8), CD (8) and expressed relative to that observed in healthy controls (10). Only miRNAs with highly altered expression (>5 or 100 -fold and 0.05-0.19 -fold for over- and under- expression, respectively; 0.001
Published: 2010
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39. T1305 Are Anti-TNFS Able to Close Enterocutaneous Fistula in Crohn's Disease?

Author: Vida, Setakhr, Seksik, Philippe, Xavier, Treton, Allez, Matthieu, De Vos, Martine, Laharie, David, Colombel, Jean-Frederic, Delchier, Jean-Charles, Vered, Abitbol, Reimund, Jean-Marie, Moreau, Jacques, Cosnes, Jacques, Lemann, Marc, Flourie, Bernard, and Bouhnik, Yoram
Published: 2010
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39 results on '"Xavier Treton"'

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