Bile Acids and Colonic Carcinogenesis

Abstract

Dietary factors are considered important environmental risk determinants for colorectal cancer development. From epidemiologic observations a high fat intake is associated positively and a high fibre intake negatively with colorectal cancer. One mechanism by which these effects are probably exerted is through bile acid metabolism. Secondary bile acids are formed after enzymatic deconjugation and dehydroxylation of the primary bile acids in the large bowel by anaerobic bacteria. It has been shown that these secondary bile acids can have tumour-promoting capacities. They are co-mutagenic and have shown co-carcinogenic properties in animal studies. Furthermore, secondary bile acids can enhance colonic epithelial proliferation. In populations and patients at high risk of developing colorectal cancer higher faecal concentrations and colonic absorption of secondary bile acids can be found. The formation of secondary bile acids increases with advancing age. Dietary fat increases and dietary fibre reduces the concentration of bile acids in the large bowel. Inhibition of secondary bile acid formation can be achieved by acidification of colonic contents.

Key Words:

• Colorectal carcinogenesis
• dietary fat and fibre
• secondary bile acids