EFFECTS OF DEOXYCHOLIC-ACID AND BUTYRATE ON MUCOSAL PROSTAGLANDIN-E2 RELEASE AND CELL-PROLIFERATION IN THE HUMAN SIGMOID COLON

Background: A high-fat, low-fiber diet resulting in increased excretio n of fecal secondary bile acids is regarded as a major risk factor for colon cancer. Incubation of human colonic biopsies with the secondary bile acid deoxycholic acid (DCA) leads to hyperproliferation with exp ansion of the proliferative zone, ie, a biomarker of increased cancer risk. Antiproliferative effects on various colon cancer cell lines, ho wever, were reported for butyrate (BUT), a fermentation product of die tary fiber. Methods: In the following in vitro study we incubated biop sies from the normal sigmoid colon of 12 patients (age 55.8 +/- 3.6 ye ars) with 5 muM DCA or a combination of 5 muM DCA plus 10 mM BUT (DCA/ BUT) and determined epithelial proliferation by bromodeoxyuridine immu nohistochemistry. As a possible mediator for the DCA effects on coloni c cell proliferation, mucosal prostaglandin E2 (PGE2) release into the incubation medium was measured by I-125-PGE2 radioimmunoassay. Result s: Incubation with DCA alone revealed a significantly higher labeling index for the whole crypt (.17 vs .11, p < .01) and for the upper 40% of the crypt (.05 vs .01, p < .01) compared with DCA/BUT. Mucosal PGE2 release during DCA/BUT incubation showed a trend toward lower values compared with DCA incubation (357.07 vs 434.29 pg/mg per hour; p = .07 ). Conclusion: The results indicate a normalization of DCA-induced hyp erproliferation of colonic epithelium by butyrate that is not clearly mediated by PGE2. Considering that nutrition affects the luminal conce ntrations of DCA and butyrate, our findings may have implications for colonic carcinogenesis.