SACCHAROMYCES-BOULARDII INHIBITS SECRETAGOGUE-MEDIATED ADENOSINE 3',5'-CYCLIC-MONOPHOSPHATE INDUCTION IN INTESTINAL-CELLS

Background/Aims: The yeast Saccharomyces boulardii inhibits the secretion induced by cholera toxin (CT) in rat jejunum. The present study was aimed at unraveling the mechanism by which S. boulardii protects intestinal cells against CT. Methods: CT-induced adenosine 3′,5′-cyclic monophosphate (cAMP) levels were measured by radioimmunoassay in intestinal epithelial cells IEC-6 or HT29-D4 cells exposed to whole yeast or to culture medium conditioned by S. boulardii (Sb-conditioned medium). Results: Sb-conditioned medium significantly reduced CT-induced cAMP levels in IEC-6 cells. This effect was eliminated by heat treatment, trypsin hydrolysis, and trichloroacetic acid precipitation of Sb-conditioned medium. When conditioned medium was fractionated on polyacrylamide gel under nondenaturing conditions, neutralizing activity was shown to be associated with a 120-kilodalton protein. The neutralizing activity was not attributable to proteolytic activity against CT. Sb-conditioned medium reduced the amount of cAMP induced by CT as well as Escherichia coli thermolabile toxin or forskolin in HT29-D4 cells. The modulation of secretagogue-induced cAMP by Sb-conditioned medium did not occur in the presence of pertussis toxin. Conclusions: These results suggest that the neutralization of CT by S. boulardii is mediated by a specific yeast protein and involves a receptor that is negatively coupled to adenylate cyclase. © 1994 American Gastroenterological Association.