Secondary bile acids and short chain fatty acids in the colon: a focus on colonic microbiome, cell proliferation, inflammation and cancer

Authors: Zeng, Huawei; SHAHID, UMAR - University Of Kansas; RUST, BRET - Oak Ridge Institute For Science And Education (ORISE); DARINA, LAZAROVA - Geisinger Medical Center; MICHAEL, BORDONARO - Geisinger Medical Center

Submitted to: International Journal of Molecular Sciences
Publication Type: Review Article
Publication Acceptance Date: 3/7/2019
Publication Date: 3/11/2019
Citation: Zeng, H., Shahid, U., Rust, B., Darina, L., Michael, B. 2019. Secondary bile acids and short chain fatty acids in the colon: a focus on colonic microbiome, cell proliferation, inflammation and cancer. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms20051214.
DOI: https://doi.org/10.3390/ijms20051214

Interpretive Summary: Colon cancer accounts for approximately 135,000 new cancer cases each year in the United States, and it is predicted that half the Western population will develop at least one colorectal tumor by the age of 70 years. Consumption of a “Western” diet that is high in fat and low in fiber causes an increase in colon cancer risk and data suggest that this increased risk may be due to elevated concentrations of secondary bile acids produced by bacteria in the colon. In contrast, short chain fatty acids, colonic-bacterial metabolites of dietary fiber, exhibit colon cancer preventive properties. With opposing effects on colonic inflammation, it is important to understand how diet (for example, dietary fiber and fat content) regulates secondary bile acids and short chain fatty acids concentrations in the colon. This article reviews the current knowledge concerning the effects of these bacterial metabolites on colonic inflammation and cancer. The information will be useful for scientists and health-care professionals who are interested in dietary fiber intake and obesity-related colon cancer prevention.

Technical Abstract: Secondary bile acids (BAs) and short chain fatty acids (SCFAs) are two major types of bacterial metabolites in the colon with opposing effects on colonic inflammation. Primary BAs play critical roles in cholesterol metabolism, lipid digestion and host-microbe interaction. Although bile acids are reabsorbed via enterohepatic circulation, primary BAs serve as substrates for bacterial biotransformation to secondary BAs in the colon. High-fat diets increase secondary BAs such as deoxycholic acid (DCA) and lithocholic acid (LCA), which are risk factors for colonic inflammation and cancer. In contrast, increased dietary fiber intake is associated with anti-inflammatory and anticancer effects. These effects may be due to the increased production of the SCFAs, acetate, propionate and butyrate, during dietary fiber fermentation in the colon., Elucidation of the molecular events by which secondary BAs and SCFAs regulate colonic cell proliferation and inflammation will lead to a better understanding of anticancer potential of dietary fiber in the context of high-fat diet-related colon cancer. This article reviews the current knowledge concerning the effects of secondary BAs and SCFAs on the proliferation of colon epithelial cells, inflammation, cancer and associated microbiome.