Environment and intestinal epithelium

Team 6

Keywords: Environmental factors, Intestinal epithelium physio(patho)logy, Regeneration, , Intestinal permeability, Inflammation

Research programs

The intestinal epithelium represents an essential functional barrier for our body, enabling the absorption of nutrients, salts, and water while providing protection against pathogens. To fulfill these functions, the cells of the intestinal mucosa renew every 5 days, subjecting the digestive tract to significant stress in controlling proliferation, differentiation, and cellular organization. Intestinal renewal is tightly regulated and depends on the spatial organization of signals from supporting mesenchymal cells, particularly the fibroblasts that sheath the crypt and sustain the intestinal epithelium.

The homeostasis—and thus the integrity—of the intestinal epithelium is constantly challenged by external environmental factors from the intestinal lumen (food additives, nutritional compounds, microbiota, etc.) and internal factors (stroma, genetic predisposition, etc.). Environmental factors that promote or worsen colonic inflammation or disrupt epithelial cell renewal are a major concern. Indeed, any disruption of intestinal homeostasis contributes to the development of chronic inflammatory bowel diseases (IBD) and tumor transformation.

The two main forms of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). One of the major complications of IBD is colorectal cancer (CRC). Additionally, sporadic colorectal cancer is the third leading cause of cancer-related mortality in industrialized countries.

Our research projects aim to investigate the impact of environmental factors—both external and internal—on the physio(patho)logy of the intestinal epithelium, the development of inflammatory processes, and carcinogenesis.

Membres

Cellular and Animal Models

Cellular Models

  • Primary cultures of human colorectal fibroblasts
  • Human and murine 3D colonic organoid primary cultures
  • Caco-2 cells stably transfected with wild-type Nod2 or mutated polymorphisms
  • Caco-2 cells stably transfected with 300A or 300T variants for ATG16L1

Animal Models

  • Murine model of colorectal cancer: Orthotopic grafting in murine models
  • Alterations in Nod2 pathways (Nod2 knockout or mutated mice)
  • Alterations in endoplasmic reticulum stress pathways (IL-1 and NOX-1 knockout mice)

Methods

  • 2D and 3D cell culture
  • Animal experimentation
  • Protein expression analysis (Western blot, etc.)
  • RT-qPCR
  • Capillary electrophoresis
  • Confocal and two-photon imaging

Publications

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

Cyclic exclusive enteral nutrition versus partial enteral nutrition to maintain long-term drug-free remission in paediatric Crohn's disease (CD-HOPE): an open-label, endpoint-blinded, randomised controlled trial. Bénédicte Pigneur, Christine Martinez‐Vinson, ..., Anne Laure Breton, et al., The Lancet Gastroenterology & Hepatology 2026. DOI: 10.1016/s2468-1253(25)00262-6

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

Perinatal exposure to nano-polystyrene: deleterious imprinting on inflammatory bowel diseases. Melvin Airaud, Amandine Roldan, ..., Lisa Isoard, ..., Sandrine Ménard, Frédérick Barreau, Particle and Fibre Toxicology 2026. DOI: 10.1186/s12989-026-00700-w

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

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

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

Human colonic organoids for understanding early events of familial adenomatous polyposis pathogenesis. Nolwenn Laborde, Alexandre Barusseaud, ..., Anne Laure Breton, Nathalie Vergnolle, ..., Frédérick Barreau, Claire Racaud‐Sultan, Emmanuel Mas, The Journal of Pathology 2024. DOI: 10.1002/path.6366

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 2023. DOI: 10.1186/s12989-023-00555-5

Intestinal involvement in lupus: From pathophysiology to therapeutic perspectives. Caroline Carlé, Emmanuel Mas, Frédérick Barreau, Lupus 2023. DOI: 10.1177/09612033231155840

Colitis Linked to Endoplasmic Reticulum Stress Induces Trypsin Activity Affecting Epithelial Functions. Núria Solà Tapias, Alexandre Denadai‐Souza, ..., Anissa Edir, ..., Emmanuel Mas, ..., Céline Deraison, Chrystelle Bonnart, Nathalie Vergnolle, Frédérick Barreau, Journal of Crohn's and Colitis 2021. DOI: 10.1093/ecco-jcc/jjab035

Titanium dioxide particles from the diet: involvement in the genesis of inflammatory bowel diseases and colorectal cancer. Frédérick Barreau, Céline Tisseyre, Sandrine Ménard, et al., Particle and Fibre Toxicology 2021. DOI: 10.1186/s12989-021-00421-2

Revisiting definition and assessment of intestinal trans-epithelial passage. Hanna Ilchmann-Diounou, Marie Buléon, ..., Sandrine Ménard, Cellular and Molecular Life Sciences 2021. DOI: 10.1007/s00018-021-04000-8

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

Reduced Intestinal Inflammation With Lumacaftor/Ivacaftor in Adolescents With Cystic Fibrosis. Candice Tétard, Marie Mittaine, ..., Emmanuel Mas, et al., Journal of Pediatric Gastroenterology and Nutrition 2020. DOI: 10.1097/mpg.0000000000002864

The Interplay Between Genetic Risk Factors and Proteolytic Dysregulation in the Pathophysiology of Inflammatory Bowel Disease. Núria Solà-Tapias, Nathalie Vergnolle, ..., Frédérick Barreau, Journal of Crohn's and Colitis 2020. DOI: 10.1093/ecco-jcc/jjaa033

Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine. Ziad Al Nabhani, Dominique D. Berrebi, ..., Frédérick Barreau, et al., Journal of Crohn's and Colitis 2019. DOI: 10.1093/ecco-jcc/jjz196