title: Probiotic Saccharomyces boulardii CNCM I-745 prevents outbreak-associated Clostridium difficile-associated cecal inflammation in hamsters.
abstract: C. difficile infection (CDI) is a common debilitating nosocomial infection associated with high mortality. Several CDI outbreaks have been attributed to ribotypes 027, 017, and 078. Clinical and experimental evidence indicates that the nonpathogenic yeast Saccharomyces boulardii CNCM I-745 (S.b) is effective for the prevention of CDI. However, there is no current evidence suggesting this probiotic can protect from CDI caused by outbreak-associated strains. We used established hamster models infected with outbreak-associated C. difficile strains to determine whether oral administration of live or heat-inactivated S.b can prevent cecal tissue damage and inflammation. Hamsters infected with C. difficile strain VPI10463 (ribotype 087) and outbreak-associated strains ribotype 017, 027, and 078 developed severe cecal inflammation with mucosal damage, neutrophil infiltration, edema, increased NF-κB phosphorylation, and increased proinflammatory cytokine TNFα protein expression. Oral gavage of live, but not heated, S.b starting 5 days before C. difficile infection significantly reduced cecal tissue damage, NF-κB phosphorylation, and TNFα protein expression caused by infection with all strains. Moreover, S.b-conditioned medium reduced cell rounding caused by filtered supernatants from all C. difficile strains. S.b-conditioned medium also inhibited toxin A- and B-mediated actin cytoskeleton disruption. S.b is effective in preventing C. difficile infection by outbreak-associated via inhibition of the cytotoxic effects of C. difficile toxins.
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Hon Wai
authors: HW
authors: Koon
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Bowei
authors: B
authors: Su
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China.
authors: Chunlan
authors: C
authors: Xu
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Caroline C
authors: CC
authors: Mussatto
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Diana Hoang-Ngoc
authors: DH
authors: Tran
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Elaine C
authors: EC
authors: Lee
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Christina
authors: C
authors: Ortiz
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Jiani
authors: J
authors: Wang
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Jung Eun
authors: JE
authors: Lee
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors: Samantha
authors: S
authors: Ho
authors: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and.
authors: Xinhua
authors: X
authors: Chen
authors: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and.
authors: Ciaran P
authors: CP
authors: Kelly
authors: Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; cpothoulakis@mednet.ucla.edu.
authors: Charalabos
authors: C
authors: Pothoulakis
mesh_terms: D000818:Animals; D002432:Cecum / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000382:microbiology / Q000517:prevention & control*; D006224:Cricetinae; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D019936:Probiotics / Q000627:therapeutic use*; D000069983:Saccharomyces boulardii; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
keywords: C. difficile; infection; probiotic