title: Persistent epithelial dysfunction and bacterial translocation after resolution of intestinal inflammation.
abstract: Epithelial secretion may play an important role in reducing bacterial colonization and translocation in intestine. If so, secretory dysfunction could result in increased susceptibility to infection and inflammation. We investigated whether long-term colonic secretory dysfunction occurs after a bout of colitis and if this is accompanied by an increase in bacterial colonization and translocation. Rats were studied 6 wk after induction of colitis with trinitrobenzene sulfonic acid when inflammation had completely resolved, and epithelial permeability was normal. Intestinal loops were stimulated with either Clostridium difficile toxin A or a phosphodiesterase inhibitor. In vitro, colonic tissue from previously sensitized rats was exposed to antigen (ovalbumin). Secretory responses to all three stimuli were suppressed in rats that had previously had colitis. These rats exhibited increased (16-fold) numbers of colonic aerobic bacteria and increased (>3-fold) bacterial translocation, similar to results in rats studied after resolution of enteritis. Postcolitis bacterial translocation was prevented by daily treatment with an inhibitor of inducible nitric oxide synthase. This study demonstrates that intestinal inflammation results in prolonged impairment of colonic epithelial secretion, which may contribute to increases in bacterial load and bacterial translocation. Epithelial dysfunction of this type could underlie an increased propensity for further bouts of inflammation, a hallmark of diseases such as inflammatory bowel disease.
authors.affiliation: Mucosal Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Asfaha
authors.forename: W K
authors.initials: WK
authors.lastname: MacNaughton
authors.forename: C B
authors.initials: CB
authors.lastname: Appleyard
authors.forename: K
authors.initials: K
authors.lastname: Chadee
authors.forename: J L
authors.initials: JL
authors.lastname: Wallace
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D001420:Bacteria, Aerobic / Q000302:isolation & purification; D001427:Bacterial Toxins / Q000494:pharmacology; D018988:Bacterial Translocation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology* / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000382:microbiology / Q000503:physiopathology; D004768:Enterotoxins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology*; D008297:Male; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010539:Permeability / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012075:Remission, Spontaneous; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D004791:Enzyme Inhibitors; C041348:tcdA protein, Clostridium difficile; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015056:1-Methyl-3-isobutylxanthine