Effect of probiotic treatment on the transition from chronic colonic inflammation to dysplasia and cancer.

Abstract

385 Background: Effective prevention of colitis-associated cancer still needs to be achieved. There is evidence that the microflora plays an important role in the progression of chronic inflammation to neoplastic transformation, so the aim of this study was to evaluate the potential efficacy of the probiotic VSL#3 in preventing this transition. Methods: Chronic colitis was induced in male Sprague Dawley rats by the administration of trinitrobenzene sulfonic acid (TNBS; 30 mg in 50% ethanol ic), followed six weeks later by reactivation with TNBS (5 mg/kg iv) for 3 days. To induce colitis-associated dysplasia and cancer the animals then received TNBS (iv) twice a week for ten weeks. One group of rats received the probiotic in drinking water (VSL#3; ∼5 billion cfu /100 gram body weight) from 1 week prior to initial colitis induction until the time of sacrifice (n = 22-23/group). After sacrifice the colons were removed and analyzed for total macroscopic damage, microscopic damage and presence of dysplasia or cancer. Tissue and serum samples were analyzed for cell proliferation and apoptosis, angiogenic factors and presence of alkaline sphingomyelinase. Results: Those animals receiving the probiotic had significantly less macroscopic and microscopic damage than the vehicle treated-controls in all areas of the colon (p < 0.05). Pathological analysis revealed that 29% of the vehicle treated animals developed carcinoma, which was confined to the proximal region. None of the probiotic treated animals developed carcinoma. Treatment with the probiotic caused a significant shift to a less severe diagnosis with no high-grade dysplasia found in either the proximal or midcolon. Treatment with the probiotic reduced crypt cell proliferation by 22% as assessed by measurement of BrdU incorporation in comparison with the vehicle treated group. Levels of the antiangiogenic factor angiostatin were higher in the probiotic treated animals (5-fold), as were serum levels of alkaline sphingomyelinase (2-fold). Conclusions: Treatment with the probiotic VSL#3 can delay the transition of chronic inflammation to dysplasia and cancer via effects on processes such as modulation of cell proliferation and angiogenesis. No significant financial relationships to disclose.