Role of Cytolethal Distending Toxin in Altered Stool Form and Bowel Phenotypes in a Rat Model of Post-infectious Irritable Bowel Syndrome

• Published in: Journal of neurogastroenterology and motility 2012-10, Vol.18 (4), p.434
• Main Authors: Venkata Pokkunuri, Mark Pimentel, Walter Morales, Sam Ryong Jee, Joel Alpern, Stacy Weitsman, Zachary Marsh, Kimberly Low, Laura Hwang, Reza Khoshini, Gillian M Barlow, Hanlin Wang, Christopher
• Format: Article
• Language: Korean
• Subjects: animal; Campylobacter infections; Cytolethal distending toxin; Inflammation
• ISSN: 2093-0879; 2093-0887

Background/Aims Campylobacter jejuni infection is a leading cause of acute gastroenteritis, which is a trigger for post-infectious irritable bowel syndrome (PI-IBS). Cytolethal distending toxin (CDT) is expressed by enteric pathogens that cause PI-IBS. We used a rat model of PI-IBS to investigate the role of CDT in long-term altered stool form and bowel phenotypes. Methods Adult Sprague-Dawley rats were gavaged with wildtype C. jejuni (C+), a C. jejuni cdtB knockout (CDT-) or saline vehicle (controls). Four months after gavage, stool from 3 consecutive days was assessed for stool form and percent wet weight. Rectal tissue was analyzed for intraepithelial lymphocytes, and small intestinal tissue was stained with anti-c-kit for deep muscular plexus interstitial cells of Cajal (DMP-ICC). Results All 3 groups showed similar colonization and clearance parameters. Average 3-day stool dry weights were similar in all 3 groups, but day-to-day variability in stool form and stool dry weight were significantly different in the C+ group vs both controls (P ＜ 0.01) and the CDT- group (P ＜ 0.01), but were not different in the CDT- vs controls. Similarly, rectal lymphocytes were significantly higher after C. jejuni (C+) infection vs both controls (P ＜ 0.01) and CDT-exposed rats (P ＜ 0.05). The counts in the latter 2 groups were not significantly different. Finally, c-kit staining revealed that DMP-ICC were reduced only in rats exposed to wildtype C. jejuni. Conclusions In this rat model of PI-IBS, CDT appears to play a role in the development of chronic altered bowel patterns, mild chronic rectal inflammation and reduction in DMP-ICC. (J Neurogastroenterol Motil 2012,18:434-442)