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Am J Physiol Gastrointest Liver Physiol 294: G599-G609, 2008. First published November 21, 2007; doi:10.1152/ajpgi.00391.2007
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INFLAMMATION/IMMUNITY/MEDIATORS

Saccharomyces boulardii interferes with Shigella pathogenesis by postinvasion signaling events

Karen L. Mumy,1,2 Xinhua Chen,1,3 Ciarán P. Kelly,3 and Beth A. McCormick1,2

1Department of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Charlestown, Massachusetts; 2Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts; and 3Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Submitted 23 August 2007 ; accepted in final form 19 November 2007

Saccharomyces boulardii is gaining in popularity as a treatment for a variety of diarrheal diseases as well as inflammatory bowel disease. This study was designed to examine the effect of this yeast on infection by Shigella flexneri, a highly infectious and human host-adapted enteric pathogen. We investigated key interactions between the bacteria and host cells in the presence of the yeast in addition to a number of host responses including proinflammatory events and markers. Although the presence of the yeast during infection did not alter the number of bacteria that was able to attach or invade human colon cancer-derived T-84 cells, it did positively impact the tight junction protein zonula occluden-2 and significantly increase the barrier integrity of model epithelia. The yeast also decreased ERK, JNK, and NF-{kappa}B activation in response to S. flexneri, events likely responsible for the observed reductions in IL-8 secretion and the transepithelial migration of polymorphonuclear leukocytes across T-84 monolayers. These results, suggesting that the yeast allowed for a dampened inflammatory response, were confirmed in vivo utilizing a highly relevant model of human fetal colonic tissue transplanted into scid mice. Furthermore, a cell-free S. boulardii culture supernatant was also capable of reducing IL-8 secretion by infected T-84 cells. These data suggest that although the use of S. boulardii during infection with S. flexneri may alleviate symptoms associated with the inflammatory response of the host, it would not prevent infection.

probiotic; inflammation; neutrophil; barrier function



Address for reprint requests and other correspondence: B. A. McCormick, Dept. of Pediatric Gastroenterology and Nutrition, 114 16th St., Rm. 3503 (114-3503), Charlestown, MA 02129 (e-mail: mccormic{at}helix.mgh.harvard.edu)







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