Epithelial microenvironment: an integrated approach to explore the mechanisms of regeneration and fibrosis in chronic inflammatory bowel diseases
EPIREPAIR — EPIthelial REPAIR mechanisms in chronic inflammation
Chronic inflammatory bowel diseases (IBD) are recurrent disorders of the gastrointestinal tract, characterized by pathological immune activation against a dysbiosis of the microbiome in a genetically predisposed individual. They are divided into two entities, Crohn’s disease and ulcerative colitis, and are characterized by waves of relapse and remission of inflammation, which lead to functional digestive disorders associated with symptoms such as bloody diarrhea, abdominal pain, and deterioration of the general condition of patients. More than 300,000 people suffer from IBD in France, and it is estimated that these diseases affect over 5 million individuals worldwide. To date, no drug treatment can cure IBD, whose pathophysiology remains imperfectly understood. It is in this context that the project developed by the team is being structured, aiming to characterize the mechanisms underlying intestinal epithelial regeneration, a key process in restoring the integrity of the mucosal barrier. Our goal is to identify the factors responsible for epithelial dysfunctions that contribute to the onset and chronicity of inflammatory bowel diseases (IBD).
Epithelial regeneration relies on the coordinated activity of intestinal stem cells, their signalling pathways, and their interactions with the inflammatory and microbial microenvironment. In parallel, the stroma, activated fibroblasts, and dysbiosis reshape the metabolic and mechanical environment in which the epithelium attempts to regenerate. Therefore, an integrated understanding of the interactions between epithelial cells, stromal cells, the immune system, and the microbiota is now considered essential for identifying new therapeutic strategies aimed at restoring efficient repair and preventing fibrosis in IBD.
Thanks to privileged access to patient samples, our team investigates these interactions using advanced organotypic models (organoids, organoids-on-chip, viable thick intestinal slices) that enable the in vitro reconstruction of epithelium–stroma–microbiota exchanges. We complement these approaches with experimental animal models that faithfully recapitulate IBD pathophysiology, such as DSS or TNBS models. Our investigations rely on both conventional techniques (qRT-PCR, Western blotting, histology, immunohistochemistry) and integrative multi-omic approaches (single-cell, transcriptomics, proteomics) to identify the cellular communication networks involved in regeneration, inflammation, and fibrotic processes.
Members
benjamin.bertin@univ-lille.fr
ORCID : 0000-0002-9160-3717
silvia.speca2@univ-lille.fr
ORCID : 0000-0001-8494-3329
madjid.tagzirt@univ-lille.fr
ORCID : 0000-0001-7914-0695
annie.standaert@univ-lille.fr
ORCID : 0000-0002-7752-3964
pauline.kerbage@chu-lille.fr
ORCID : 0000-0002-7684-6067
A few representative publications
Original articles:
Maxime Costa, Muriel Pottier, Marie Jacob, Pauline Zarnitzky, Benjamin Segain, Martin Figeac, Shéhérazade Sebda, Frédéric Leprêtre, Bertrand Meresse, Julie Demaret, Benoit Foligné, Annie Standaert, Benjamin Bertin. Relevance of mouse and human IBD patient-derived colon organoids to investigate intestinal macrophage differentiation. J Leukoc Biol. 2025 Apr 23;117(4):qiaf004. doi: 10.1093/jleuko/qiaf004.
Adele Ponzoni, Silvia Speca, Matthew Hartle, Amandine Gerstenberg, Aurore Tomezyk, Victor Senechal, Shane Karnik, Laurent Dubuquoy, David Launay, Rebecca Deprez-Poulain, Mathieu Gaudin, Corinne Ramos, Benoit Deprez. An untargeted metabolomic study using MALDI-mass spectrometry imaging reveals region-specific biomarkers associated with bowel inflammation. Metabolomics. 2024 Dec 14;21(1):5. doi: 10.1007/s11306-024-02200-4.
Caroline Valibouze, Silvia Speca, Caroline Dubuquoy, Florian Mourey, Lena M'Ba, Lucil Schneider, Marie Titecat, Benoît Foligné, Michaël Genin, Christel Neut, Philippe Zerbib, Pierre Desreumaux. Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats. World J Gastroenterol. 2023 Feb 7;29(5):851-866. doi: 10.3748/wjg.v29.i5.851.
Dina Chokr, Marjorie Cornu, Christel Neut, Clovis Bortolus, Rogatien Charlet, Pierre Desreumaux, Silvia Speca, Boualem Sendid. Adherent invasive Escherichia coli (AIEC) strain LF82, but not Candida albicans, plays a profibrogenic role in the intestine. Gut Pathog. 2021 Jan 28;13(1):5. doi: 10.1186/s13099-021-00401-z.
Mathurin Fumery, Silvia Speca, Audrey Langlois, Anne-Marie Davila, Caroline Dubuquoy, Marta Grauso, Anthony Martin Mena, Martin Figeac, Daniel Metzger, Christel Rousseaux, Jean-Frederic Colombel, Laurent Dubuquoy, Pierre Desreumaux, Benjamin Bertin. Peroxisome proliferator-activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut. EMBO Mol Med. 2017 Nov;9(11):1471-1481.doi: 10.15252/emmm.201707795.
Anthony Martin Mena, Audrey Langlois, Silvia Speca, Lucil Schneider, Pierre Desreumaux, Laurent Dubuquoy, Benjamin Bertin. The Expression of the Short Isoform of Thymic Stromal Lymphopoietin in the Colon Is Regulated by the Nuclear Receptor Peroxisome Proliferator Activated Receptor-Gamma and Is Impaired during Ulcerative Colitis. Front Immunol. 2017 Sep 4:8:1052.doi: 10.3389/fimmu.2017.01052.
Silvia Speca, Christel Rousseaux, Caroline Dubuquoy, Florian Rieder, Antonella Vetuschi, Roberta Sferra, Ilaria Giusti, Benjamin Bertin, Laurent Dubuquoy, Eugenio Gaudio, Pierre Desreumaux, Giovanni Latella. Novel PPARγ Modulator GED-0507-34 Levo Ameliorates Inflammation-driven Intestinal Fibrosis. Inflamm Bowel Dis. 2016 Feb;22(2):279-92. doi: 10.1097/MIB.0000000000000618.
Guillaume Bouguen, Audrey Langlois, Madjid Djouina, Julien Branche, Dine Koriche, Edmone Dewaeles, Alice Mongy, Johan Auwerx, Jean-Frederic Colombel, Pierre Desreumaux, Laurent Dubuquoy, Benjamin Bertin. Intestinal steroidogenesis controls PPARγ expression in the colon and is impaired during ulcerative colitis. Gut. 2015 Jun;64(6):901-10. doi: 10.1136/gutjnl-2014-307618.
Revues:
Ian C Lawrance, Gerhard Rogler, Giorgos Bamias, Christine Breynaert, Jon Florholmen, Gianluca Pellino, Shimon Reif, Silvia Speca, Giovanni Latella. Cellular and Molecular Mediators of Intestinal Fibrosis. J Crohns Colitis. 2017 Dec 4;11(12):1491-1503. doi:10.1016/j.crohns.2014.09.008.
Guillaume Bouguen, Laurent Dubuquoy, Pierre Desreumaux, Thomas Brunner, Benjamin Bertin. Intestinal steroidogenesis. Steroids. 2015 Nov;103:64-71. doi:10.1016/j.steroids.2014.12.022.
Benjamin Bertin, Laurent Dubuquoy, Jean-Frédéric Colombel, Pierre Desreumaux. PPAR-gamma in ulcerative colitis: a novel target for intervention. Curr Drug Targets. 2013 Nov;14(12):1501-7. doi: 10.2174/13894501113149990162.
Benjamin Bertin, Pierre Desreumaux, Laurent Dubuquoy. Obesity, visceral fat and Crohn's disease. Curr Opin Clin Nutr Metab Care. 2010 Sep;13(5):574-80. doi:10.1097/MCO.0b013e32833cf0f4.