Chemopreventive effect of a probiotic preparation on the development of preneoplastic and neoplastic colonic lesions: an experimental study.

ABSTRACT

BACKGROUND/AIMS: A number of studies have suggested a key role played by certain resident gut bacteria in the development of large bowel cancer. The aim of the present study was to test the effect of a novel symbiotic preparation, which has been recently shown to beneficially modify gut ecosystem and systemic immunity, on either preneoplastic and neoplastic changes in a colon carcinogenesis model. METHODOLOGY: Sprague-Dawley rats were fed a standard diet for 1 week and then were randomly assigned to three groups. The control diet was given to groups A and B, whereas in group C, the same diet plus 2 mL of a probiotic mixture was given throughout the experiment. Thirty rats (groups B, C) each received a weekly subcutaneous injection of azoxymethane at a dose of 15 mg/kg of body weight for 10 weeks. Group A served as a control group and received a subcutaneous injection of saline for 10 weeks. Forty-five rats were sacrificed at 3-week observation and 60 rats at 20-week observation for assessing metaphase index together with aberrant crypt foci and intestinal immune system markers from one hand and tumor occurrence from the other, respectively. RESULTS: Group A showed a significantly increased metaphase index either in aberrant crypt foci or in "normal appearing" crypts when compared to group A (p < 0.01). Group B rats caused a significant decrease at both sites (p < 0.05). The numbers of lymphocytes derived from the mesenteric lymph nodes in group B rats were significantly decreased (p < 0.01) as compared to either control and to group C. The percentage of CD8 lymphocytes in group C was significantly higher than that in group B. Group C showed a significantly reduced ratio of aberrant crypt foci/colon and of aberrant crypt per colon and per each single focus (p < 0.05). A total of 18 (90%) group B and 10 (50%) group C rats had colon tumors, this difference was significant. The mean number of colon tumors per rat was 2.2 and 1.0 in group B and C, respectively. CONCLUSIONS: Effective probiotics treatment, through mechanisms still to be fully elucidated (decreased fecal pH, specific reduction of carcinogenetic bacterial enzymes, modulation of gut-associated and systemic immune system etc.) has the potential to exert significant antimutagenic properties against colon cancer.