title: Role of Cytolethal Distending Toxin in Altered Stool Form and Bowel Phenotypes in a Rat Model of Post-infectious Irritable Bowel Syndrome.
abstract: OBJECTIVE
  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. jejunicdtB 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.
authors.affiliation: GI Motility Program, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Venkata
authors.initials: V
authors.lastname: Pokkunuri
authors.forename: Mark
authors.initials: M
authors.lastname: Pimentel
authors.forename: Walter
authors.initials: W
authors.lastname: Morales
authors.forename: Sam-Ryong
authors.initials: SR
authors.lastname: Jee
authors.forename: Joel
authors.initials: J
authors.lastname: Alpern
authors.forename: Stacy
authors.initials: S
authors.lastname: Weitsman
authors.forename: Zachary
authors.initials: Z
authors.lastname: Marsh
authors.forename: Kimberly
authors.initials: K
authors.lastname: Low
authors.forename: Laura
authors.initials: L
authors.lastname: Hwang
authors.forename: Reza
authors.initials: R
authors.lastname: Khoshini
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Barlow
authors.forename: Hanlin
authors.initials: H
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Chang
keywords: Campylobacter infections; Cytolethal distending toxin; Inflammation; Models, animal