Dose–Response Relationship and Mechanism of Action of Saccharomyces boulardiiin Castor Oil-Induced Diarrhea in Rats

For biotherapeutic agents, there is a lack of information on dose–response relationships and mechanism of action. The present study was designed to address these issues for Saccharomyces boulardiiusing the rat model of castor oil-induced diarrhea. A single dose of Saccharomyces boulardiiat 12 × 1010CFU/kg of viable cells given 1 hr before castor oil administration significantly reduced the onset of diarrhea. Repeated ingestion of the yeast, twice daily between 1.2 and 12 × 1010CFU/kg for 5 days before castor oil, showed a dose–response relationship. The percentage of rats with diarrhea decreased and a stronger protection was afforded by the repeated treatment. The mechanism of action of Saccharomyces boulardiiin this model was investigated with two classes of antagonists, naloxone and L-arginine. The effect of Saccharomyces boulardiiwas not inhibited by naloxone but was significantly reduced by L-arginine. This last result suggests a novel mechanism of action for Saccharomyces boulardiiinvolving a possible inhibition of nitric oxide production by the yeast.