Degree Type


Date of Award


Degree Name

Doctor of Philosophy


Veterinary Pathology

First Advisor

Darin M. Madson

Second Advisor

Michael Yaeger


Clostridium difficile is a gram-positive, anaerobic, spore-forming bacterium and considered the major cause of antibiotic-associated diarrhea in many countries worldwide. Clostridium difficile infection (CDI) in humans causes pseudomembranous colitis. Clinical signs range from mild diarrhea to potentially toxic megacolon, bowel perforation, peritonitis and even death. Naturally occurring C. difficile infection has also been described in several non-human species including pigs, horses, primates, rabbits, rats, dogs and cats. The majority of cases, both humans and animals, are associated with disequilibrium of commensal intestinal microbiota which is often attributed to antibiotic treatments. The pathogenesis of CDI is tightly associated with the cellular effects of toxin A and toxin B and the immunologic response associated with these toxins. Despite the importance of these toxins, the specific role of each toxin on the pathophysiology of disease is not yet completely understood.

Clostridium difficile is one of the major causes of enteric disease in neonate piglets, yet risk factors associated with C. difficile infection in piglets are unknown. Furthermore, there is a general lack of prevention strategies available for swine medicine. In our first study we used snatch farrowed neonatal pigs to investigate the role of different inoculum doses, antimicrobial therapy, and piglet-age on the development of disease. Our results indicated that C. difficile dosage appears to be an important risk factor for CDI; 10 day-old pigs can develop disease associated with C. difficile, and antibiotic administration following inoculation is not a major contributor for disease in neonatal piglets. In our second study we investigated the use of lactobacillus and a non-toxigenic C. difficile strain (NTCD) as probiotics to prevent CDI in piglets. Our results showed that NTCD reduces the incidence of CDI in piglets. Toxin levels, mesocolonic edema and histopathologic lesions were reduced when compared to positive control piglets. Usage of Lactobacillus sp. did not reveal any clear benefits. Lastly, we developed a gut-loop ligate model in 7 day-old piglets to study the pathophysiology of toxin A and B alone or in combination in different segments of small intestine and colon. Results demonstrated that the porcine intestinal loop model has the potential to become a valuable resource to further investigate the pathophysiology and associated-inflammatory response associated with individual toxins within different segments of the intestines. Also, there was a synergistic effect when toxins were administered simultaneously. Loops treated with toxin A only had slightly higher histologic scores when compared to toxin B alone.


Copyright Owner

Paulo H. Elias Arruda



File Format


File Size

121 pages