Relationship between Fecal Bile Acids and the Occurrence of Colorectal Neoplasia in Experimental Murine Ulcerative Colitis

Abstract

Objective: The possible role of fecal bile acids in colorectal carcinogenesis in ulcerative colitis has been reported. In this study, we investigated the relationship between fecal bile acids and the occurrence of colorectal neoplasia in experimental murine colitis induced by dextran sulfate sodium. Methods: Colorectal neoplasia in experimental colitis was induced by dextran sulfate sodium subsequent to a single azoxymethane pretreatment. Fecal bile acids were analyzed by gas-liquid chromatography. Results: Multiple high-grade dysplasias (intramucosal adenocarcinoma) and inflammatory changes were seen in all mice administered dextran sulfate sodium and azoxymethane. Inflammatory changes were also observed in all mice given dextran sulfate sodium only, while neither tumor nor inflammatory changes were detected in any of the control mice. Significant increases in cholic acid were observed in the mice of the colorectal tumor and experimental colitis groups during the experimental period, while in the control mice, no significant changes in fecal bile acids were obseved. Conclusion: It is suggested that fecal cholic acid and colitis may be intimately related to the development of colorectal neoplasia in this experimental model of murine colitis as well as in ulcerative colitis.

Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies

“…Increased concentrations of fecal bile acids could lead to DNA damage and other damage to cells. Animal models have indicated that fecal bile acids could promote carcinogenesis of colorectum [61].…”

Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor

“…Reduced spillover of bile acids into the colon could improve the chologenic component of diarrhoea in these patients and might even reduce the risk of colon cancer imposed by increased exposure of the colonic mucosa to bile acids. 41 GR belongs to the group of classic nuclear steroid hormone receptors that bind to DNA as homodimers following activation by steroid hormones. A second nuclear receptor that is activated by corticosteroids is the human steroid/ xenobiotic receptor SXR and its rodent orthologue PXR.…”

Germinated barley foodstuff, a prebiotic product, ameliorates inflammation of colitis through modulation of the enteric environment

“…26 Bile acid may increase the risk of colonic dysplasia or cancer, especially in UC patients. 27,28 Also, these patients may have higher levels of carcinogenic secondary bile acids and, thus, be more likely to develop cancer on the right side of the colon, where secondary bile acid concentrations are highest. 37,38 Therefore, it is important to investigate whether GBF eliminates bile acids in vivo.…”