Environnement et épithélium intestinal
Équipe 6
Mot-clés : Facteurs environnementaux, physio(patho)logie de l’épithélium intestinal, Régénération, Perméabilité intestinale, Inflammation
Programme de recherche
L’épithélium intestinal représente une barrière fonctionnelle essentielle pour notre organisme en permettant l’absorption des nutriments, des sels et de l’eau tout en assurant une protection contre les agents pathogènes. Afin d’assurer ces fonctions, les cellules de la muqueuse intestinale se renouvellent tous les 5 jours, soumettant le tractus digestif à un stress important dans le contrôle de la prolifération, la différenciation et l’organisation cellulaire de l’épithélium intestinal. Le renouvellement intestinal est étroitement contrôlé et dépend notamment de l’organisation spatiale des signaux émanant des cellules mésenchymateuses de soutien, en particulier les fibroblastes gainant la crypte et soutenant l’épithélium intestinal. L’homéostasie, et donc l’intégrité de l’épithélium intestinal, est constamment mise à l’épreuve par les facteurs environnementaux ‘extérieurs’ provenant de la lumière intestinale (additifs alimentaires, composés nutritionnels, microbiote…) ou ‘intérieurs’ (stroma, prédisposition génétiques…). Les facteurs environnementaux favorisant et/ou aggravant l’inflammation colique ou affectant le processus de renouvellement des cellules épithéliales sont une source majeure de préoccupation. En effet, toute altération de l’homéostasie intestinale va intervenir dans la mise en places des maladies inflammatoires chroniques de l’intestin (MICI) et la transformation tumorale.
Les deux principales formes de MICI sont la maladie de Crohn (MC) et la rectocolite hémorragique (RCH). L’une des complications majeures des MICI est le cancer colorectal. D’autre part, le cancer colorectal sporadique (CRC) est la 3ème cause de mortalité par cancer dans les pays industrialisés.
Nos projets de recherche ont pour but d’étudier l’impact environnemental (‘extérieur’ ou ‘intérieur’) sur la physio(patho)logie de l’épithélium intestinal, le développement du processus inflammatoire et la carcinogénèse.
Membres
Modèles cellulaires et animaux
Modèles cellulaires
- Primocultures de fibroblastes colorectaux humains
- Primocultures organoïdes du côlon 3D humain et murin
- Cellules Caco-2 transfectées de manière stable avec du Nod2 wt ou un polymorphisme muté.
- Cellules Caco-2 transfectées de manière stable avec des variants 300A ou 300T pour ATG16L1.
Modèles animaux
- Modèle murin de cancer colorectal: Greffe orthotopique dans des modèles murins
- Altérations des voies Nod2 (souris KO ou mutées pour Nod2)
- Altérations de la voie de stress du réticulum endoplasmique (souris KO pour IL-1 et NOX-1)
Méthodes
- Culture de cellules 2D et 3D
- Expérimentation animale
- Expression protéique (Western-blot…)
- RT-qPCR
- Électrophorèse capillaire
- Imagerie confocale et bi-photonique
Publications
Article type:
Intestinal toxicity of functionalized polystyrene nanoplastics in NOD2 models of Crohn’s disease susceptibility. Manon Dussol, Sandrine Ménard, ..., Frédérick Barreau, et al., Frontiers in Toxicology 2026. DOI: 10.3389/ftox.2026.1839932
Exclusive enteral nutrition containing transforming growth factor‐β improves intestinal barrier function in a colitis mouse model. Kawthar Boumessid, Vickie Lacroix, ..., Frédérick Barreau, Emmanuel Mas, Journal of Pediatric Gastroenterology and Nutrition 2026. DOI: 10.1002/jpn3.70517
Su1472 COLITIS-PRIMED CIRCULATING T CELLS DRIVE SMALL INTESTINAL BARRIER FUNCTION THROUGH MICROBIOTA-DEPENDENT MECHANISMS. Talal Nabhani, Arthur Mauduit, et al., Gastroenterology 2026. DOI: 10.1016/s0016-5085(26)02679-x
Su1472 COLITIS-PRIMED CIRCULATING T CELLS DRIVE SMALL INTESTINAL BARRIER FUNCTION THROUGH MICROBIOTA-DEPENDENT MECHANISMS. Talal Nabhani, Arthur Mauduit, et al., Gastrointestinal Endoscopy 2026. DOI: 10.1016/s0016-5107(26)02610-6
Fatty acids from adipocyte lipolysis stimulate insulin secretion. Camille Fournes-Fraresso, Émilie Courty, ..., Stéphanie Cassant‐Sourdy, et al., bioRxiv 2026. DOI: 10.64898/2026.05.13.724851
Main genetic factors associated with inflammatory bowel diseases and their consequences on intestinal permeability: involvement in gut inflammation. Arthur Mauduit, Emmanuel Mas, ..., Sandrine Ménard, Frédérick Barreau, Journal of Gastroenterology 2025. DOI: 10.1007/s00535-025-02289-x
Deciphering the interplay between biology and physics with a finite element method-implemented vertex organoid model: A tool for the mechanical analysis of cell behavior on a spherical organoid shell. Julien Laussu, Déborah Michel, ..., Frédérick Barreau, Emmanuel Mas, et al., PLOS Computational Biology 2025. DOI: 10.1371/journal.pcbi.1012681
Dietary intake remains unchanged while nutritional status improves in children and adults with cystic fibrosis on Elexacaftor/Tezacaftor/Ivacaftor. Raphaël Enaud, Jeanne Languepin, ..., Emmanuel Mas, et al., Clinical Nutrition 2025. DOI: 10.1016/j.clnu.2025.04.027
Evolution of hepatobiliary involvement in cystic fibrosis children on CFTR modulators. Mélanie Auvray, Nolwenn Laborde, ..., Frédérick Barreau, ..., Emmanuel Mas, Journal of Cystic Fibrosis 2025. DOI: 10.1016/j.jcf.2025.05.003
Intestinal involvement in graft versus host disease in children: An overview by the ESPGHAN Gastroenterology Committee. Marina Vincent, Amit Assa, ..., Emmanuel Mas, Journal of Pediatric Gastroenterology and Nutrition 2025. DOI: 10.1002/jpn3.70087
Colitis-primed circulating T cells drive small intestinal barrier function through Nod2, microbiota and myosin light chain kinase-dependent mechanisms. Arthur Mauduit, Talal Nabhani, ..., Emmanuel Mas, Frédérick Barreau, et al., bioRxiv 2025. DOI: 10.1101/2025.07.10.663215
Drugs in focus: Budesonide and its role in paediatric gastrointestinal disorders. Sohail Aziz, Maria Giovanna Puoti, ..., Emmanuel Mas, et al., Journal of Pediatric Gastroenterology and Nutrition 2025. DOI: 10.1002/jpn3.70245
Skin Manifestations of Adult-Onset Immunodeficiencies. Sandrine Ménard, Robert Gniadecki, et al., Diseases of Blood and Skin 2025. DOI: 10.1007/978-3-031-65292-9_16
Toxicity of polystyrene particles to mice and in vitro models of intestinal cells, both healthy and with genetic susceptibility to Crohn’s disease. Manon Dussol, Sandrine Ménard, ..., Frédérick Barreau, et al., 2025. DOI: 10.2139/ssrn.5550796
Human colonic organoids for understanding early events of familial adenomatous polyposis pathogenesis. Nolwenn Laborde, Alexandre Barusseaud, ..., Nathalie Vergnolle, ..., Frédérick Barreau, Claire Racaud‐Sultan, Emmanuel Mas, The Journal of Pathology 2024. DOI: 10.1002/path.6366
Correction: Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life. Caroline Carlé, Delphine Boucher, ..., Sandrine Ménard, ..., Emmanuel Mas, ..., Frédérick Barreau, Particle and Fibre Toxicology 2024. DOI: 10.1186/s12989-024-00570-0
Toxicity of Polystyrene Particles to Mice and in Vitro Models of Intestinal Cells, Both Healthy and with Genetic Susceptibility to Crohn's Disease. Manon Dussol, Sandrine Ménard, ..., Frédérick Barreau, et al., 2024. DOI: 10.2139/ssrn.4964764
Tu1735 IMPACT OF PERINATAL EXPOSITION TO PLASTIC ON INFLAMMATORY BOWEL DISEASES AND ADVERSE FOOD REACTIONS IN MICE OFFSPRING. Melvin Airaud, Amandine Roldan, ..., Sandrine Ménard, Frédérick Barreau, Gastroenterology 2024. DOI: 10.1016/s0016-5085(24)03672-2
Deleterious imprinting of perinatal exposure to nano-polystyrene on inflammatory bowel diseases. Melvin Airaud, Amandine Roldan, ..., Lisa Isoard, Emmanuel Mas, ..., Sandrine Ménard, Frédérick Barreau, bioRxiv 2024. DOI: 10.1101/2024.12.20.629591
P340 Despite an unchanged energy intake, both pediatric and adult cystic fibrosis (CF) patients experienced improvement in their body mass index (BMI) under ETI modulator therapy. M. Lagarrigues, A. Arrouy, Emmanuel Mas, et al., Journal of Cystic Fibrosis 2024. DOI: 10.1016/s1569-1993(24)00636-2
P268 Evolution of hepatobiliary involvement in cystic fibrosis children on CFTR modulators. Marie Auvray, Nolan Joseph Laborde, Emmanuel Mas, et al., Journal of Cystic Fibrosis 2024. DOI: 10.1016/s1569-1993(24)00569-1
Cold-induced thermogenesis requires neutral-lipase-mediated intracellular lipolysis in brown adipocytes. Étienne Mouisel, A Bodon, ..., Stéphanie Cassant‐Sourdy, et al., Cell Metabolism 2024. DOI: 10.1016/j.cmet.2024.10.018
Rôle sexuellement dimorphique du récepteur aux œstrogènes ER alpha hépatocytaire dans la progression vers la stéato-hépatite métabolique. Blandine Tramunt, Marie-Lou Calmy, ..., Stéphanie Cassant‐Sourdy, et al., Annales d'Endocrinologie 2024. DOI: 10.1016/j.ando.2024.08.090
Pediatric Magnet Ingestion, Diagnosis, Management, and Prevention. Ahmed Nugud, Christos Tzivinikos, ..., Emmanuel Mas, et al., Journal of Pediatric Gastroenterology and Nutrition 2023. DOI: 10.1097/mpg.0000000000003702
Cross-Talk Between the Intestinal Epithelium and Salmonella Typhimurium. Sandrine Ménard, Sonia Lacroix‐Lamandé, ..., Agnès Wiedemann, Frontiers in Microbiology 2022. DOI: 10.3389/fmicb.2022.906238
Diagnosis, Management, and Prevention of Button Battery Ingestion in Childhood. Amani Mubarak, Marc A. Benninga, ..., Emmanuel Mas, et al., Journal of Pediatric Gastroenterology and Nutrition 2021. DOI: 10.1097/mpg.0000000000003048
Gastrointestinal Perspective of Coronavirus Disease 2019 in Children—An Updated Review. Amit Assa, Marc A. Benninga, ..., Emmanuel Mas, et al., Journal of Pediatric Gastroenterology and Nutrition 2021. DOI: 10.1097/mpg.0000000000003204
Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis. Julien Pujo, Camille Petitfils, ..., Frédérick Barreau, ..., Éric Oswald, et al., Gut 2020. DOI: 10.1136/gutjnl-2020-321173
Psychological Stress, Intestinal Barrier Dysfunctions, and Autoimmune Disorders: An Overview. Hanna Ilchmann-Diounou, Sandrine Ménard, Frontiers in Immunology 2020. DOI: 10.3389/fimmu.2020.01823
The food contaminant, deoxynivalenol, modulates the Thelper/Treg balance and increases inflammatory bowel diseases. Delphine Payros, Sandrine Ménard, et al., Archives of Toxicology 2020. DOI: 10.1007/s00204-020-02817-z
Characterization of Human Colon Organoids From Inflammatory Bowel Disease Patients. Emilie d'Aldebert, Muriel Quaranta, ..., Claire Racaud‐Sultan, Emmanuel Mas, Céline Deraison, Nathalie Vergnolle, Frontiers in Cell and Developmental Biology 2020. DOI: 10.3389/fcell.2020.00363
A Systematic Review and Meta-analysis of Paediatric Inflammatory Bowel Disease Incidence and Prevalence Across Europe. Stephen Roberts, Kym Thorne, ..., Emmanuel Mas, et al., Journal of Crohn's and Colitis 2020. DOI: 10.1093/ecco-jcc/jjaa037
FAK activity in cancer‐associated fibroblasts is a prognostic marker and a druggable key metastatic player in pancreatic cancer. Sonia Zaghdoudi, Emilie Decaup, ..., Stéphanie Cassant‐Sourdy, et al., EMBO Molecular Medicine 2020. DOI: 10.15252/emmm.202012010
Vegan diet in children and adolescents. Recommendations from the French-speaking Pediatric Hepatology, Gastroenterology and Nutrition Group (GFHGNP). Julie Lemale, Emmanuel Mas, et al., Archives de Pédiatrie 2019. DOI: 10.1016/j.arcped.2019.09.001
Overview and Comparison of Intestinal Organotypic Models, Intestinal Cells, and Intestinal Explants Used for Toxicity Studies. Marc Maresca, Philippe Pinton, ..., Sandrine Ménard, et al., Current Topics in Microbiology and Immunology 2018. DOI: 10.1007/82_2018_142
NOD2 Expression in Intestinal Epithelial Cells Protects Toward the Development of Inflammation and Associated Carcinogenesis. Audrey Ferrand, Ziad Al Nabhani, ..., Emmanuel Mas, ..., Frédérick Barreau, Cellular and Molecular Gastroenterology and Hepatology 2018. DOI: 10.1016/j.jcmgh.2018.10.009
Management of Juvenile Polyposis Syndrome in Children and Adolescents. Shlomi Cohen, Warren Hyer, Emmanuel Mas, et al., Journal of Pediatric Gastroenterology and Nutrition 2018. DOI: 10.1097/mpg.0000000000002246
Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study. Fabienne Charbit‐Henrion, Marianna Parlato, ..., Emmanuel Mas, et al., Journal of Crohn's and Colitis 2018. DOI: 10.1093/ecco-jcc/jjy068
Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917. Teresa Pérez, Julien Pujo, ..., Frédérick Barreau, ..., Éric Oswald, et al., Nature Communications 2017. DOI: 10.1038/s41467-017-01403-9
Nod2: The intestinal gate keeper. Ziad Al Nabhani, Gilles Dietrich, ..., Frédérick Barreau, PLOS Pathogens 2017. DOI: 10.1371/journal.ppat.1006177
Continuous*in vitro*exposure of intestinal epithelial cells to E171 food additive causes oxidative stress, inducing oxidation of DNA bases but no endoplasmic reticulum stress. Marie Dorier, David Béal, ..., Frédérick Barreau, et al., Nanotoxicology 2017. DOI: 10.1080/17435390.2017.1349203
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism. Thomas Farge, Estelle Saland, ..., Stéphanie Cassant‐Sourdy, et al., Cancer Discovery 2017. DOI: 10.1158/2159-8290.cd-16-0441
*Nod2*Deficiency Leads to a Specific and Transmissible Mucosa-associated Microbial Dysbiosis Which Is Independent of the Mucosal Barrier Defect. Ziad Al Nabhani, Patricia Lepage, ..., Frédérick Barreau, Journal of Crohn's and Colitis 2016. DOI: 10.1093/ecco-jcc/jjw095
