ENRICHMENT OF THE MORE HYDROPHILIC BILE-ACID URSODEOXYCHOLIC ACID IN THE FECAL WATER-SOLUBLE FRACTION AFTER FEEDING TO RATS WITH COLON POLYPS

We recently showed that feeding the cytoprotective bile acid ursodeoxy cholic acid (UDCA) to rats resulted in significant reduction in polyps and especially cancers, both in number and size (D. L. Earnest et at, Cancer Res., 54: 5071-5074, 1994). Because fecal secondary bite acids [particularly deoxycholic acid (DCA)] are considered to promote forma tion of colon adenomas and cancer, we have now attempted to find a re lationship between polyp reduction and fecal secondary bile acids afte r feeding UDCA to these rats. We examined the fecal bile acids in rats with polyps and compared them with fecal bile acids in control rats a nd also determined the bile acid composition in fecal aqueous phase, w hich is in direct contact with the colon epithelium and may be physiol ogically more active. Treatment with azoxymethane did not significantl y alter fecal bile acid composition in the rats. Cholic acid feeding r esulted in greatly increased proportions of DCA (82% of total bile aci ds versus 18% in control rats). On the other hand, UDCA feeding signif icantly reduced the proportion of fecal DCA (2% in control rats fed UD CA and 3% in rats also treated with azoxymethane). In control rats, 96 % of the bile acids were present in the water-insoluble fraction and 4 % in the water-soluble fraction. The major insoluble bile acids includ ed DCA and hyodeoxycholic acid (73% of total bile acids). In contrast, the muricholic acids were concentrated in the soluble fraction (37%), When 0.4% UDCA was added to the diet, lithocholic acid increased in t he insoluble fraction (40 versus 1%), but the hydrophilic UDCA and mur icholic acids were enriched in the water-soluble fraction (37 and 43%, respectively). Thus, the hydrophobic bile acids were distributed pred ominantly in the water-insoluble fraction, whereas the hydrophilic bil e acids were distributed preferentially in the water-soluble fraction. These data suggest that UDCA may prevent colon tumors and polyps by c ountering the toxic effect of DCA and enhancing the possible cytoprote ctive effects of UDCA and muricholic acids in the water-soluble fracti on in the feces of rat.