Persistent epithelial dysfunction and bacterial translocation after resolution of intestinal inflammation

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• Epithelial secretion is crucial for limiting intestinal bacterial colonization and translocation.
• Secretory dysfunction may heighten susceptibility to infection and inflammation.

Purpose of the Study:

• To determine if long-term colonic secretory dysfunction persists after colitis resolution.
• To investigate if this dysfunction correlates with increased bacterial colonization and translocation.

Main Methods:

• Rats with resolved colitis (induced by trinitrobenzene sulfonic acid) were studied 6 weeks post-induction.
• Intestinal loops were stimulated with Clostridium difficile toxin A or a phosphodiesterase inhibitor.
• Colonic tissue was exposed to ovalbumin antigen in vitro.

Main Results:

• Secretory responses to all stimuli were significantly suppressed in rats with a history of colitis.
• These rats showed a 16-fold increase in colonic aerobic bacteria and a >3-fold increase in bacterial translocation.
• Treatment with an inducible nitric oxide synthase inhibitor prevented post-colitis bacterial translocation.

Conclusions:

• Intestinal inflammation causes prolonged impairment of colonic epithelial secretion.
• This secretory dysfunction may contribute to increased bacterial load and translocation.
• Such epithelial dysfunction could predispose individuals to recurrent inflammation, characteristic of inflammatory bowel disease.