Pathologic changes involve three main phases. These include the establishment of infection in the ileum and cecum, the ascension of the pathogen to the liver via the portal circulation, and hematogenous spread to other tissues such as the myocardium. This triad of organ involvement is the hallmark of Tyzzer's disease. In mice, the affected intestine is thickened, edematous, and hyperemic. Necrotic foci develop in the affected intestine, liver, and myocardium.
Lesions are similar in rats, except that megaloileitis is a common finding.
More recently, others have demonstrated increased susceptibility to a toxigenic isolate of C. piliforme in nude mice and have concluded that T cells may also play a role in immunity to Tyzzer's disease. Those authors acknowledge that the cytotoxin produced by the isolate may have contributed to the severity of clinical disease and lesions. Effects on research include increased mortality, alteration of the pharmacokinetics of warfarin and trimethoprim, and alteration of the activity of hepatic transaminases. In addition, experimental manipulations have been reported to provoke or exacerbate clinical disease caused by C. piliforme. Natural infection of laboratory mice and rats could severely alter the findings of studies involving the gastrointestinal and cardiopulmonary systems.