Biliary bile acid profiles in familial adenomatous polyposis

Abstract

Patients with familial adenomatous polyposis have an excess risk for adenomas and cancers of the upper and lower gastrointestinal tract. In the upper intestine these lesions occur mainly around the ampulla of Vater and they parallel mucosal exposure to bile. In view of this finding and of evidence that bile acids play a role in colorectal carcinogenesis, biliary bile acid profiles were determined in 29 patients with familial adenomatous polyposis (12 before colectomy, 17 after colectomy) and in 28 patients without familial adenomatous polyposis (all with colons in situ). Patients with familial adenomatous polyposis had a higher total biliary bile acid concentration than the others. The bile of patients with polyposis had a greater proportion of chenodeoxycholic acid and a lower proportion of deoxycholic acid than did the bile of patients without polyposis. The ratio of chenodeoxycholic acid and its metabolite lithocholic acid to cholic acid and its metabolite deoxycholic acid, which is related to subsequent bile acid profiles in the colon, was higher in patients with polyposis. Because bile acids influence cellular proliferation, these findings may be of importance with respect to intestinal adenoma and cancer growth.

Pancreaticoduodenectomy for advanced duodenal and ampullary adenomatosis in familial adenomatous polyposis

“…Duodenal adenomas can undergo dysplastic change, most often in the second and third parts of the duodenum, 11 where prolonged contact with bile acids may lead to mutational changes in the surrounding mucosa 12–14 . However, only approximately 5% of all duodenal polyps will undergo malignant change, 10 via the adenoma–carcinoma sequence, 4–7 and the cumulative incidence of duodenal cancer in FAP is 4.5% at 57 years 9 …”

Sulphation of lithocholic acid in the colon-carcinoma cell line CaCo-2

“…The intestinal uptake of fat is, among other factors, dependent on bile acids. Primary and secondary bile acids have been suggested to contribute to the development of colon cancer [2][3][4]. Increased levels of secondary bile acids, in particular, lithocholic acid (LA), in the colon is related to colorectal neoplasia [5].…”

Microbiota-Associated Metabolites and Related Immunoregulation in Colorectal Cancer

“…The ratio of primary/secondary BAs depends on the situation. For healthy people, the ratio in the duodenal fluid is about 5 to 6 [109,110], the ratio in feces is around 4, with primary BAs accounting for 80% [111] and the ratio of DCA metabolites to CA metabolites in serum is close to 5 [112]. However, for patients with colorectal cancer or polyps, the proportion of secondary BAs significantly increased [113], especially the LCA.…”