title: Saccharomyces boulardii improves intestinal cell restitution through activation of the α2β1 integrin collagen receptor.
abstract: Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on α2β1 integrin activity was assessed using adhesion assays and the analysis of α2β1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates α2β1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of α2β1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases.
authors.affiliation: Inserm, UMR 911, Centre de Recherche en Oncologie et Oncopharmacologie, Marseille, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Canonici
authors.forename: Carole
authors.initials: C
authors.lastname: Siret
authors.forename: Emilie
authors.initials: E
authors.lastname: Pellegrino
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Pontier-Bres
authors.forename: Laurent
authors.initials: L
authors.lastname: Pouyet
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Montero
authors.forename: Carole
authors.initials: C
authors.lastname: Colin
authors.forename: Dorota
authors.initials: D
authors.lastname: Czerucka
authors.forename: Véronique
authors.initials: V
authors.lastname: Rigot
authors.forename: Frédéric
authors.initials: F
authors.lastname: André
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D051379:Mice; D019936:Probiotics / Q000494:pharmacology* / Q000627:therapeutic use*; D038981:Receptors, Collagen / Q000378:metabolism*; D012440:Saccharomyces
chemical_list: D038982:Integrin alpha2beta1; D038981:Receptors, Collagen