Pseudomembranous colitis in Clostridium difficile-monoassociated rats.

Germfree rats were monoassociated with either a toxin-producing strain of Clostridium difficile (Tox+) or a variant of this strain (ToxR) which produced much less toxin (1/10,000) in vivo and in vitro. Monoassociation of germfree rats with C. difficile Tox+ resulted in mortality (17%) and in pathology to the small and large intestines, livers, and lungs. Cecal filtrates from the Tox+-monoassociated rats were cytotoxic for tissue culture cells. The cytotoxicity of cecal filtrates could be blocked by sera from Tox+-monoassociated rats. Monoassociation of rats with C. difficile ToxR resulted in no deaths or pathology, and much less toxin was detected in the cecal filtrates of these animals than in those of rats colonized with the Tox+ strain. This gnotobiotic model may be useful for investigating the etiology, prophylaxis, therapy, and exacerbation of C. difficile-induced pseudomembranous colitis.