Clostridium difficile and mesocolon edema syndrome of neonatal pigs: studies of pathogenesis in a gnotobiotic pig model

Mesocolon edema syndrome is recognized as a common cause of diarrhea in pigs less than 2 weeks of age, and has been associated with neonatal colonization by Clostridium difficile, C. perfringens, or often as a combined infection. In the United States, C. perfringens type A is increasing in prevalence, but C. difficile colonization and subsequent enterotoxemia is still an important cause of the syndrome. In this study, we directly examined the events of colonization of the lower intestinal tract by C. difficile in a gnotobiotic pig model to gain a preliminary understanding of pathogenesis for the syndrome.

Two groups, totaling 36 pigs, were delivered by caesarian section into flexible film isolators and associated with a defined normal intestinal flora free of clostridial organisms and other enteric pathogens. Pigs were then assigned to treatment groups, based on variation of timing of antibiotic prophylaxis, antibiotic therapy, probiotic prophylaxis, and challenge with either toxigenic or non-pathogenic C. difficile. Evaluation of colonic colonization and lesion development was then pursued through the use of selective culture, genome detection, measurement of host substrate compounds such as bile acids by HPLC, and measurement of host response through tissue cytokine assays, histopathology, and immunohistochemistry.

In this model, colonization by C. difficile was easily established and verified by culture and genomic endpoints. Variation of early colonic and mesocolonic lesions was observed between groups, which depended on sequence and nature of antibiotic or probiotic treatments, as well as the timing of challenge with toxigenic C. difficile.

Colonization of the lower intestine in this gnotobiotic model was largely dependent on timing and dosage, while lesion initiation appeared to more related to prior manipulation of the microflora through probiotic and antibiotic administration.

Disclosure of Interest: None Declared.