Bile Acid Concentrations, Cytotoxicity, and pH of Fecal Water from Patients with Colorectal Adenomas

Publisher Website
Google Scholar
Abstract
In the multistage model of human colorectaltumorigenesis, both genetic and environmental factorsplay an important role. The identity of theenvironmental factors involved, however, still remainsto be elucidated. As fecal bile acids are proposed ascandidates, we compared the concentration of bile acidsin fecal water from patients at different risk ofdeveloping colorectal cancer. In addition, pH of fecal water as well as its cytotoxicity toHT-29 colonic cells was determined. The high-risk groupconsisted of individuals diagnosed with one or more(tubulo)villous colorectal adenomas larger than 1 cm in diameter and containing moderate or severedysplasia (N = 20). Subjects with colorectal adenomassmaller than 1 cm and showing only minor dysplasia wereassigned to the medium risk group (N = 19). The control group consisted of persons with normalfindings by colonoscopy (N = 25). The results show nosignificant differences in fecal water bile acidconcentrations between the three groups. However, 46% of the observed cytotoxicity is explained in aregression model that includes pH and the concentrationsof deoxycholic acid, cholic acid, and ursodeoxycholicacid. The pH of fecal water is found to be significantly lower in the high risk group as compared to thecontrols, suggesting that a relatively high fecal pH hasa protective effect on the development of colorectaladenomas. Although hyperproliferation as a result of cytotoxicity has been suggested tocontribute to tumor formation in the colon, thepH-dependent cytotoxicity of bile acids in fecal waterwas not found to be associated with adenoma formation inthe present study.