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.
Highlights
The colonic epithelium forms a continuous physical and functional barrier that protects the internal environment of the body from the fluctuating external milieu
The motogenic effect of Saccharomyces boulardii (Sb) supernatant was quite similar to that observed using type I insulin-like growth factor (IGF-I), a well known inductor of cell restitution (Figure 1C) [24]
We verified by flow cytometry analysis that T84 cells express both a2b1and av integrins indicating that the reduced effect of Sb in this cell line was not associated with a lack of integrin expression
Summary
The colonic epithelium forms a continuous physical and functional barrier that protects the internal environment of the body from the fluctuating external milieu. Various substances including dietary elements, gastrointestinal secretory products and drugs are known to disrupt this epithelial barrier, leading to the shedding of epithelial cells and the development of wounds [1]. Infection of the colonic mucosa by bacterial pathogens including Shigella, Salmonella or Clostridium difficile results in the development of acute intestinal inflammatory diseases and destruction of the intestinal epithelium [3,4]. As with other epithelia of the gastrointestinal tract, the repair of damaged colonic mucosa initially requires cell migration to restore epithelial continuity [1]. This process, termed restitution, is followed by the proliferation and subsequent maturation and differentiation of the cells, allowing the restoration of normal architecture and absorptive/secretory function
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