1.Role of Cytolethal Distending Toxin in Altered Stool Form and Bowel Phenotypes in a Rat Model of Post-infectious Irritable Bowel Syndrome.
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 CHANG
Journal of Neurogastroenterology and Motility 2012;18(4):434-442
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.
Adult
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Animals
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Bacterial Toxins
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Campylobacter Infections
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Campylobacter jejuni
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Colon
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Gastroenteritis
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Humans
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Inflammation
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Interstitial Cells of Cajal
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Irritable Bowel Syndrome
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Lymphocytes
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Models, Animal
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Phenotype
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Rats
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Rats, Sprague-Dawley
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Weights and Measures