Response of the IRD intestinal epithelial cell line to Clostridium difficile toxins A and B in rats. Effect of Saccharomyces boulardii

: In vivo, Clostridium difficile acts by releasing 2 toxins: toxin A, an enterotoxin, and toxin B, a cytotoxin. This study was performed to determine: a) whether the rat epithelial intestinal cell line IRD 98 responds to Clostridium difficile toxin A and B; b) whether the yeast Saccharomyces boulardii has an effect on this model. Evaluation of 3H-thymidine incorporation into IRD 98 cells exposed to toxin B revealed that DNA synthesis was inhibited for low concentrations (10 ng/ml). For higher concentrations, DNA synthesis was not modified. Evaluation of 14C-leucine incorporation into IRD 98 cells exposed to toxin B revealed that this toxin affected protein synthesis. Whereas cholera toxin stimulates adenylate cyclase in IRD 98 cells, cAMP levels in cells exposed to various quantities of toxin A was similar to that in control cells. As opposed to cholera toxin, which does not affect the cytoskeletal structure of IRD 98 cells, 7 micrograms/ml of toxin A and even smaller amounts of toxin B (1 ng/ml) were found to cause structural alterations by immunofluorescence studies. Prior exposition of cells to Saccharomyces boulardii reduced or prevented the rounding of cells in the presence of these toxins. IRD 98 cells can thus be considered a good model for in vitro investigation of the effects of Clostridium difficile toxins A and B, and findings suggest that Saccharomyces boulardii has a protective effect against the action of these toxins.