Research Group : Environment & INteSTinal Epithelium INteractions
- from stem cells to associated (Dys)Functions -

AUDREY FERRAND &  
​FRÉDÉRICK BARREAU

Team Leader
  • Envirronemental factors 
  • Pathophysiology of the intestinal epithelium
  • Inflammation
  • Carcinogenesis
  • Intestinal permeability 

RESEARCH DESCRIPTION

The intestinal epithelium is an essential functional barrier for our body by allowing the absorption of nutrients, salts and water while providing protection against pathogens. To ensure these functions, the cells of the intestinal mucosa are renewed every 5 days, subjecting the digestive tract to significant stress in the control of proliferation, differentiation and cellular organization of the intestinal epithelium. Intestinal turnover is tightly controlled and depends in particular on the spatial organization of the signals emanating from the mesenchymal support cells, in particular the fibroblasts encasing the crypt and supporting the intestinal epithelium. 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 ...) or 'internal' (stroma genetic predisposition ...). Environmental factors promoting and / or aggravating colonic inflammation or affecting the process of epithelial cell turnover are a major source of concern. Indeed, any alteration of intestinal homeostasis will intervene in the establishment of chronic inflammatory bowel disease (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. On the other hand, sporadic colorectal cancer (CRC) is the third leading cause of cancer death in industrialized countries.
     Our research projects aim to study the environmental impact ('outside' or 'inside') on the physio (pathology) of the intestinal epithelium, the development of the inflammatory process and carcinogenesis.

Members 

ANIMAL AND CELLULAR MODELS / METHODS

Cellular models :
- Human colorectal fibroblast primocultures
- Human and murine 3D colon organoid primocultures
- Caco-2 cells stabely transfected with Nod2 wt or mutated polymorphism.
- Caco-2 cells stabely transfected with 300A or 300T variants for ATG16L1.

Animal models :
- Sub-cutaneous or caecum orthotopic grafting in murine models
- Alterations of the Nod2 pathways (mice KO or mutated for Nod2)
- Alterations of the endoplasmic reticulum stress pathway (mice KO for IL-1 and NOX-1)
Methods:
- 2D and 3D cell culture
- Animal experimentation
- Protein expression (Western-blot, invalidation ...)
- RT-qPCR
- Capillary Electrophoresis
- Confocal and bi-photon imaging.

publications

NOD2 expression in intestinal epithelial cells protects toward the development of inflammation and associated carcinogenesis
Ferrand A, Al Nabhani Z, Solà Tapias N, Mas E, Hugot JP, Barreau F, Cell Mol Gastroenterol Hepatol. 2019;7(2):357-369. doi: 10.1016/j.jcmgh.2018.10.009. Epub 2018 Oct 23. Review.

Sustainable Positive Response to Sirolimus in Juvenile Polyposis of Infancy.
Quaranta M, Laborde N, Ferrand A, Danjoux M, Vergnolle N, Barreau F, Racaud-Sultan C, Mas E. J Pediatr Gastroenterol Nutr. 2018 Oct 16. doi: 10.1097/MPG.0000000000002179.PMID: 30334931

Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a PAR1- and PAR4-dependent mechanism.
Sébert M, Denadai-Souza A, Quaranta M, Racaud-Sultan C, Chabot S, Lluel P, Monjotin N, Alric L, Portier G, Kirzin S, Bonnet D,Ferrand A*, Vergnolle N*. (*: Co-last authors) Br J Pharmacol. 2018 Jun 30.  doi: 10.1111/bph.14430. PMID: 29959891
 
Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917. Pérez-Berezo T, Pujo J, Martin P, Le Faouder P, Galano JM, Guy A, Knauf C, Tabet JC, Tronnet S, Barreau F, Heuillet M, Dietrich G, Bertrand-Michel J, Durand T, Oswald E, Cenac N. Nat Commun. 2017 Nov 3;8(1):1314. doi: 10.1038/s41467-017-01403-9. PMID: 29101366 Free PMC Article Similar articles

Oral Administration of the Probiotic Strain Escherichia coli Nissle 1917 Reduces Susceptibility to Neuroinflammation and Repairs Experimental Autoimmune Encephalomyelitis-Induced Intestinal Barrier Dysfunction. Secher T, Kassem S, Benamar M, Bernard I, Boury M, Barreau F, Oswald E, Saoudi A. Front Immunol. 2017 Sep 14;8:1096. doi: 10.3389/fimmu.2017.01096. eCollection 2017. PMID:28959254 Free PMC Article Similar articles

Complementary Roles of Nod2 in Hematopoietic and Nonhematopoietic Cells in Preventing Gut Barrier Dysfunction Dependent on MLCK Activity. Al Nabhani Z, Montcuquet N, Roy M, Dussaillant M, Hugot JP, Barreau F. Inflamm Bowel Dis. 2017 Jul;23(7):1109-1119. doi: 10.1097/MIB.0000000000001135. PMID:28520587 Similar articles

.Nod2: The intestinal gate keeper. Al Nabhani Z, Dietrich G, Hugot JP, Barreau F. PLoS Pathog. 2017 Mar 2;13(3):e1006177. doi: 10.1371/journal.ppat.1006177. eCollection 2017 Mar. Review. PMID:28253332 Free PMC Article Similar articles

Anti-inflammatory and anticancer effects of flavonol glycosides from Diplotaxis harra through GSK3β regulation in intestinal cells.
Nasri I, Chawech R, Girardi C, Mas E, Ferrand A, Vergnolle N, Fabre N, Mezghani-Jarraya R, Racaud-Sultan C. Pharm Biol. 2017 Dec;55(1):124-131. Epub 2016 Sep 22. PMID:27925497 Similar articles

Mu and delta opioid receptor knockout mice show increased colonic sensitivity. Reiss D, Ceredig RA, Secher T, Boué J, Barreau F, Dietrich G, Gavériaux-Ruff C. Eur J Pain. 2017 Apr;21(4):623-634. doi: 10.1002/ejp.965. Epub 2016 Oct 17. PMID:27748566 Similar articles

FUNDINGS