Role of Bile Acids in Gastrointestinal Carcinogenesis

Role of Bile Acids in Gastrointestinal Carcinogenesis

US Gastroenterology & Hepatology Review Volume 4 Issue 2
Published: October 2009
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Bile acids are normal components of the lumenal contents of the gastrointestinal (GI) tract where they enable absorption of lipids, cholesterol, and fat-soluble vitamins. Upon ingestion of fat, the release of bile acids into the duodenum from the gall bladder is increased. For example, total median bile acid concentration in the fecal water of 25 individuals without colonic neoplasia on their normal diet was 0.18mM,1 while total median bile acid concentration in the fecal water of seven individuals after five days on a controlled high-fat diet was 0.36mM.2 Thus, a high-fat diet causes increased levels of bile acids in the fecal water. This is likely related to the association of high levels of dietary fats with colon cancer, though it may be specific types of fat that are most important,3,4 and specific human genotypes that may be most vulnerable.5

At high physiologic concentrations, bile acids can cause oxidative/nitrosative stress, DNA damage, apoptosis, and mutation. Furthermore, frequently repeated and prolonged exposure of tissues to high physiological levels of bile acids can lead to the generation of genomic instability, development of apoptosis resistance and, ultimately, cancer. Evidence for an important role of bile acids in carcinogenesis in the different organs of the gastrointestinal (GI) tract is summarized below. In addition, in Figure 1, we outline a possible sequence of events leading to GI cancer that may result from excessive repeated exposure to high levels of bile acids from a consistently high-fat diet, consumed over long periods.



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Keywords:
Gastrointestinal Carcinogenesis, Bile acids, GI,

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