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062 SACCHAROMYCES BOULARDII ATTENUATES MUCOSAL INFLAMMATION AND MAINTAINS COLONIC BARRIER FUNCTION IN CITROBACTER RODENTIUM-INDUCED COLITIS IN MICE X Wu, BA Vallance, K Madsen, A Buchan, K Jacobson Saccharomyces boulardii, a non-pathogenic yeast, has received increasing attention in the prevention and treatment of infectious and inflammatory bowel diseases. The aim of the present study was to examine the ameliorating effects of Saccharomyces boulardii on mouse colitis induced by Citrobacter rodentium in vivo and to further explore the relationship in vitro.
Child and Family Research Institute, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia
METHODS: C57BL/6 mice received 2.5 × 108 C. rodentium by gavage on day 0, followed by S. boulardii (25 mg/ml; 5 × 108 live cells) gavaged twice daily from day 2 to day 9. Animals weights were monitored every second day and all animals were sacrificed on day 10. The colons were removed and assessed for epithelial barrier function by Ussing chambers, histology and myeloperoxidase activity. The bacterial epithelial attachment was assessed in vitro and in vivo by immunofluorescence and Western blot for the type III effector protein, Tir.
RESULTS: S. boulardii treatment significantly attenuated the weight loss (13% decrease from baseline at day 4 vs 32%) with full recovery by day 10, ameliorated the crypt cell hyperplasia (234.7±7.2 µm vs 297.8±17.6 µm), the histological damage score (0.5±0.2 vs 1.25±0.5) and elevated myeloperoxidase activity of infected mice (2.1±0.4 U/mg vs 4.7±0.9 U/mg). Moreover, oral administration of S. boulardii attenuated the increase in mannitol flux (17.2±5.0 nm/cm2/hr vs 31.2±8.2 nm/cm2/hr) and normalized the response to forskolin (98.0±11.6 µA/cm2 vs 63.2±8.3 µA/cm2) in infected mice colons. S. boulardii also significantly reduced the number of adherent colonic C. rodentium by 82%. Furthermore, reduced bacterial adherence was associated with a marked reduction in Tir expression and secretion.
CONCLUSION: This study demonstrated that S. boulardii ameliorated the inflammatory sequelae associated C. rodentium infection and maintained colonic epithelial barrier integrity through a reduction in bacterial epithelial interaction. This action was mediated through a reduction in type III effector protein expression and secretion. Further determination of the mechanism of action of S. boulardii might lead to the development of a novel therapy in the management of inflammatory bowel disease.
Supported by CCFC (Canada)