Role of Cytolethal Distending Toxin in Altered Stool Form and Bowel Phenotypes in a Rat Model of Post-infectious Irritable Bowel Syndrome.
- Author:
Venkata POKKUNURI
1
;
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 CHANG
Author Information
1. GI Motility Program, Cedars-Sinai Medical Center, Los Angeles, California, USA. Christopher.chang@cshs.org
- Publication Type:Original Article
- Keywords:
Campylobacter infections;
Cytolethal distending toxin;
Inflammation;
Models, animal
- MeSH:
Adult;
Animals;
Bacterial Toxins;
Campylobacter Infections;
Campylobacter jejuni;
Colon;
Gastroenteritis;
Humans;
Inflammation;
Interstitial Cells of Cajal;
Irritable Bowel Syndrome;
Lymphocytes;
Models, Animal;
Phenotype;
Rats;
Rats, Sprague-Dawley;
Weights and Measures
- From:Journal of Neurogastroenterology and Motility
2012;18(4):434-442
- CountryRepublic of Korea
- Language:English
-
Abstract:
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- roup (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.
