Inhibition of Chronic Ulcerative Colitis-associated Adenocarcinoma Development in Mice by VSL#3

Background:Colorectal cancer is the most severe complication in inflammatory bowel disease. This study aimed to investigate the effects of the probiotic VSL#3 when administered as either preventive or concurrent treatment in the progression from chronic colitis to colon cancer.Methods:Mice were exposed to 5, 10, and 15 cycles of dextran sulfate sodium (DSS); each cycle consisted of 0.7% DSS for 1 week followed by distilled water for 10 days. VSL#3 was administered either from 2 weeks before the colitis induction or from the first day of the colitis until being killed. After each period, macroscopic and histological studies, as well as analysis of inflammatory and tumor biomarkers, were performed.Results:Prophylactic or concurrent VSL#3 administration attenuated the disease activity index score and colon inflammation after 5, 10, and 15 cycles of DSS, as well as reduced the histological alterations and the incidence of colonic dysplastic lesions at the 3 periods studied. None of the animals receiving VSL#3 as a concurrent treatment developed carcinoma, which is in contrast to 5% and 20% of the mice following preventive VSL#3 administration, developing carcinoma at the 10th and the 15th cycles of DSS, respectively. In addition, the probiotic reduced the proliferating cell nuclear antigen labeling index, tumor necrosis factor alpha, interleukin-1, interleukin-6 production, cyclooxygenase-2 expression, and increased interleukin-10 levels in colon tissue at the 3 periods assayed.Conclusions:VSL#3 administration reduced chronic inflammation and prevented or delayed the development of dysplasia and carcinoma in a mouse model of chronic colitis-associated cancer.