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AN ANIMAL MODEL OF IRRITABLE BOWEL SYNDROME
AWG Waugh, BC Sydora, J Doyle, RN Fedorak
Division of Gastroenterology, University of Alberta, Edmonton, Alberta
BACKGROUND: Lactobacillus plantarum 299v (LP) (TuZen®, Ferring Canada) is a probiotic bacteria with known beneficial effects to the gastrointestinal tract and in patients with irritable bowel syndrome (IBS) [Nobaek et al AJG 2000; Niedzielin et al EJGH 2001]. A form of IBS has been shown to occur as a consequence of a gastrointestinal inflammatory event. Oil of mustard (OM) contains allyl isothiocyante which, when administered rectally to mice induces a transient colitis lasting 7 days followed by a diffuse motility disturbance, similar to that seen in humans with post-inflammatory IBS.
AIM: The aim of the study was to examine the effect of LP administration on colonic inflammation and motility in the OM post-inflammatory IBS model.
METHODS: A 1% OM (v/v) in 30% ETOH (v/v) solution was administrated by rectal enema on day zero. Control mice received only the 30% ETOH solution. In both OM and control mice LP, 1×109 cfu/d, was fed by oral gavage for 28d, beginning 7d prior to OM [pre-treatment group], or for 13d, beginning 8d after OM [post-treatment]. Colonic injury was assessed at 4d and 20d after OM via histological injury score and mucosal IFNgamma levels. Small intestinal transit was assessed via the dye-detection technique, expressed as a ratio of dye transit per total small intestinal length.
RESULTS: Pre-treatment with LP in OM mice: (1) improved the histologic injury score and reduced IFNgamma levels at 4d (9.8±1.9ng/g) and 20d (9.8±2.1ng/g) vs controls (27.8±14.8 and 46.1±15.7ng/g, respectively, p=0.08)); and (2) normalized intestinal transit at 20d (0.45±0.05) vs controls (0.33+0.08) (p=0.16). Similarly, post-treatment with LP in OM mice: (1) improved IFNgamma levels at 20d (24.1±9.1ng/g) vs controls (46.1±15.7ng/g) (p=0.x19) and, (2) improved, but not normalized, intestinal transit at 20d (0.43±0.03) vs control (0.33±0.08) (p=0.16)
CONCLUSION: Oil of Mustard administration induces a reproducible transient intestinal inflammatory response and long lasting reduction in small intestinal motility, similar to that seen in human IBS. Lactobacillus plantarum 299v improves both the intestinal injury and inflammatory response, and the delayed intestinal transit in this IBS model. Pretreatment appears more effective than treatment following the inflammatory event. Lactobacillus plantarum 299v may have a therapeutic role in post-inflammatory irritable bowel syndromes.