title: Saccharomyces cerevisiae CNCM I-3856 prevents colitis induced by AIEC bacteria in the transgenic mouse model mimicking Crohn's disease.
abstract: BACKGROUND
  Adherent-invasive Escherichia coli (AIEC), which colonize the ileal mucosa of patients with Crohn's disease (CD), are able to adhere to and invade intestinal epithelial cells. Overexpression of the glycoprotein CEACAM6 on host cells favors AIEC attachment and inflammation. We investigated the ability of Saccharomyces cerevisiae CNCM I-3856 to inhibit AIEC adhesion and to reduce colitis.
  
  
  METHODS
  Adhesion experiments were performed on T84 cells and on enterocytes from patients with CD with AIEC LF82 in the presence of S. cerevisiae. Colonization and symptoms of colitis were assessed in LF82-infected transgenic CEABAC10 mice treated with live S. cerevisiae or S. cerevisiae derivatives. Proinflammatory cytokines were quantified by enzyme linked immunosorbent assay. Intestinal permeability was assessed by measuring the 4 kDa dextran-FITC flux in the serum.
  
  
  RESULTS
  S. cerevisiae strongly inhibited LF82 adhesion to T84 cells and to the brush border of CD enterocytes. Yeasts decreased LF82 colonization and colitis in CEABAC10 mice and restored barrier function through prevention of the LF82-induced expression of pore-forming tight junction claudin-2 at the plasma membrane of intestinal epithelial cells. These effects were accompanied by a decrease in proinflammatory cytokines IL-6, IL-1β, and KC release by the gut mucosa. Yeast derivatives exerted similar effects on LF82 colonization and colitis demonstrating that yeast viability was not essential to exert beneficial effects.
  
  
  CONCLUSIONS
  S. cerevisiae yeasts reduce colitis induced by AIEC bacteria in CEACAM6-expressing mice. Such a probiotic strategy could be envisaged in a subgroup of patients with CD abnormally expressing CEACAM6 at the ileal mucosa and therefore susceptible to being colonized by AIEC bacteria.
authors.affiliation: *M2iSH, UMR 1071 Inserm/University of Auvergne, Clermont-Ferrand, France; †INRA USC 2018, Clermont-Ferrand, France; ‡Centre Hospitalier Universitaire, Clermont-Ferrand, France; and §Lesaffre International, Direction of Research and Development, Marcq-en-Baroeul, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Sivignon
authors.forename: Amélie
authors.initials: A
authors.lastname: de Vallée
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barnich
authors.forename: Jérémy
authors.initials: J
authors.lastname: Denizot
authors.forename: Claude
authors.initials: C
authors.lastname: Darcha
authors.forename: Georges
authors.initials: G
authors.lastname: Pignède
authors.forename: Pascal
authors.initials: P
authors.lastname: Vandekerckove
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001422:Bacterial Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D003092:Colitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D020895:Enterocytes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D058851:GPI-Linked Proteins / Q000502:physiology; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D012441:Saccharomyces cerevisiae / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C470556:Ceacam10 protein, mouse; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C575659:Gm5893 protein, mouse