This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Batta, A. K. Articles by Earnest, D. L. Search for Related Content PubMed PubMed Citation Articles by Batta, A. K. Articles by Earnest, D. L.

Enrichment of the More Hydrophilic Bile Acid Ursodeoxycholic Acid in the Fecal Water-soluble Fraction after Feeding to Rats with Colon Polyps¹

Department of Medicine and the Liver Institute, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103 [A. K. B., G. S.]; Department of Veterans Affairs New Jersey Health Care System, East Orange, New Jersey 07018 [G. S.]; Department of Medicine, University of Arizona, Tucson, Arizona 85727 [H. H., D. A., D. L. E.]; and Department of Medicine, University of Chicago, Chicago, Illinois 60637 [T. A. B.]

We recently showed that feeding the cytoprotective bile acid ursodeoxycholic acid (UDCA) to rats resulted in significant reduction in polyps and especially cancers, both in number and size (D. L. Earnest et al., Cancer Res., 54: 5071–5074, 1994). Because fecal secondary bile acids [particularly deoxycholic acid (DCA)] are considered to promote formation of colon adenomas and cancer, we have now attempted to find a relationship between polyp reduction and fecal secondary bile acids after 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 and also determined the bile acid composition in fecal aqueous phase, which is in direct contact with the colon epithelium and may be physiologically more active. Treatment with azoxymethane did not significantly alter fecal bile acid composition in the rats. Cholic acid feeding resulted in greatly increased proportions of DCA (82% of total bile acids versus 18% in control rats). On the other hand, UDCA feeding significantly reduced the proportion of fecal DCA (2% in control rats fed UDCA 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 included 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 the insoluble fraction (40 versus 1%), but the hydrophilic UDCA and muricholic acids were enriched in the water-soluble fraction (37 and 43%, respectively). Thus, the hydrophobic bile acids were distributed predominantly in the water-insoluble fraction, whereas the hydrophilic bile acids were distributed preferentially in the water-soluble fraction. These data suggest that UDCA may prevent colon tumors and polyps by countering the toxic effect of DCA and enhancing the possible cytoprotective effects of UDCA and muricholic acids in the water-soluble fraction in the feces of rat.

¹ This work was supported in part by USPHS Grant HL-17818, a grant from the Veterans Affairs Research Service (Washington, DC), and National Cancer Institute Grant POI-CA-41108.

² To whom requests for reprints should be addressed, at GI Section (15A), VA Medical Center, 385 Tremont Avenue, East Orange, NJ 07018-1095. Phone: (201) 676-1000, ext. 2289; Fax: (201) 676-2991.

Received 9/15/97. Accepted 2/16/98.

This article has been cited by other articles:

				B. C. Wertheim, M. E. Martinez, E. L. Ashbeck, D. J. Roe, E. T. Jacobs, D. S. Alberts, and P. A. Thompson Physical Activity as a Determinant of Fecal Bile Acid Levels Cancer Epidemiol. Biomarkers Prev., May 1, 2009; 18(5): 1591 - 1598. [Abstract] [Full Text] [PDF]

				T Kitiyakara and R W Chapman Chemoprevention and screening in primary sclerosing cholangitis Postgrad. Med. J., May 1, 2008; 84(991): 228 - 237. [Abstract] [Full Text] [PDF]

				D. S. Alberts, M. E. Martinez, L. M. Hess, J. G. Einspahr, S. B. Green, A. K. Bhattacharyya, J. Guillen, M. Krutzsch, A. K. Batta, G. Salen, et al. Phase III Trial of Ursodeoxycholic Acid To Prevent Colorectal Adenoma Recurrence J Natl Cancer Inst, June 1, 2005; 97(11): 846 - 853. [Abstract] [Full Text] [PDF]

				L. M. Hess, M. F. Krutzsch, J. Guillen, H-H. S. Chow, J. Einspahr, A.K. Batta, G. Salen, M. E. Reid, D. L. Earnest, and D. S. Alberts Results of a Phase I Multiple-Dose Clinical Study of Ursodeoxycholic Acid Cancer Epidemiol. Biomarkers Prev., May 1, 2004; 13(5): 861 - 867. [Abstract] [Full Text] [PDF]

				S. Khare, S. Cerda, R. K. Wali, F. C. von Lintig, M. Tretiakova, L. Joseph, D. Stoiber, G. Cohen, K. Nimmagadda, J. Hart, et al. Ursodeoxycholic Acid Inhibits Ras Mutations, Wild-type Ras Activation, and Cyclooxygenase-2 Expression in Colon Cancer Cancer Res., July 1, 2003; 63(13): 3517 - 3523. [Abstract] [Full Text] [PDF]

				R. K. Wali, D. Stoiber, L. Nguyen, J. Hart, M. D. Sitrin, T. Brasitus, and M. Bissonnette Ursodeoxycholic Acid Inhibits the Initiation and Postinitiation Phases of Azoxymethane-induced Colonic Tumor Development Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1316 - 1321. [Abstract] [Full Text] [PDF]

				B. Y. Tung, M. J. Emond, R. C. Haggitt, M. P. Bronner, M. B. Kimmey, K. V. Kowdley, and T. A. Brentnall Ursodiol Use Is Associated with Lower Prevalence of Colonic Neoplasia in Patients with Ulcerative Colitis and Primary Sclerosing Cholangitis Ann Intern Med, January 16, 2001; 134(2): 89 - 95. [Abstract] [Full Text] [PDF]

				D. S. Alberts A Unifying Vision of Cancer Therapy for the 21st Century J. Clin. Oncol., November 1, 1999; 17(90001): 13 - 21. [Full Text] [PDF]

				A. K. Batta, G. Salen, K. R. Rapole, M. Batta, P. Batta, D. Alberts, and D. Earnest Highly simplified method for gas-liquid chromatographic quantitation of bile acids and sterols in human stool J. Lipid Res., June 1, 1999; 40(6): 1148 - 1154. [Abstract] [Full Text]