The role of butyrate in human colonic epithelial cells: an energy source or inducer of differentiation and apoptosis?

Colo-rectal cancer is a major health problem in industrialized countries and the high incidence has been linked with the diet (Burkitt, 1971). The colonic epithelium is in direct contact with dietary factors present in the lumen and these factors may affect the pattern of growth, differentiation and cell death within the tissue. Epidemiological studies suggest that a low-fat, high-fibre diet is protective for colo-rectal cancer (Burkitt, 1971; Howe et al. 1992) whereas a diet high in red meat and saturated fat and low in dietary fibre and vegetables is associated with an increased risk for colo-rectal cancer. Colon cancers most often develop from premalignant adenomas (sometimes referred to as polyps) which, in turn, are derived from the normal colonic epithelium. Sandler et al. (1993) conducted an epidemiological study which showed that diets high in fat and low in carbohydrates and fibre not only increased the risk for colo-rectal cancer, but also for the precursor adenomas. The diet, therefore, may be particularly important for those individuals predisposed to large-bowel cancer and a better understanding of how dietary factors may influence colon cancer risk may lead to dietary intervention. Dietary fibre is composed of non-polysaccharides such as lignin and the NSP, carbohydrates such as cellulose, pectin and gums which are derived from plant cell walls. Fibre escapes digestion in the stomach and small intestine, as do oligosaccharides and some resistant starches (Silvester et al. 1995) but in the large bowel symbiotic bacteria are able to ferment these carbohydrates, releasing the short-chain fatty acids (butyrate, propionate and acetate) as a by-product of this metabolism. There are a number of ways in which fibre could protect against colo-rectal cancer. It increases transit rate and bulk, thereby potentially decreasing exposure to carcinogens in the diet. It adsorbs carcinogens, modifies intestinal microflora (and may, therefore, alter bile salt and carcinogen metabolism), decreases faecal bile salt excretion and lowers the colonic pH, as well as increasing the concentrations of the short-chain fatty acids in the large bowel (McIntyre et al. 1993). The diet is complex, and in epidemiological studies it is difficult to unravel the effects of individual components. For example, diets high in animal fat may also contain carcinogens generated during cooking of meat. Diets low in fruit and vegetable fibre may be low in vitamins which have antioxidant effects (for review, see Rogers et al. 1993). Animal studies have helped in this respect in that diets can be more carefully controlled, but the results are variable because of the types of fibre administered (Levin, 1992). Dietary wheat bran results in higher concentrations of butyrate than either oat bran or guar gum (Kashtan et al. 1992; McIntyre et al. 1993).