Editors' ChoiceCancer

Why a High-Fiber Diet Prevents Cancer

Sci. Signal.  13 Jan 2015:
Vol. 8, Issue 359, pp. ec8
DOI: 10.1126/scisignal.aaa6561

A diet high in fiber promotes colon health, and commensal bacteria in the gut may be protective against colon cancer. The bacterium Butyrivibrio fibrisolvens ferments fiber into short-chain fatty acids such as butyrate. Butyrate is an inhibitor of histone deacetylases (HDACs), which function in the epigenetic control of gene expression. Donohoe et al. examined the mechanistic link between a high-fiber diet and gut microbiota in colon cancer using inbred mice engineered to have a strictly controlled gut microbiome (see also Sebastián and Mostoslavsky). Mice fed a high-fiber diet that were colonized with B. fibrisolvens had increased colonic luminal amounts of butyrate and when exposed to a chemical carcinogen developed fewer, smaller, and less advanced colon tumors than did mice fed a low-fiber diet, mice that were colonized with a metabolically deficient strain of the bacteria, or mice that lacked the bacterium. Mice fed a tributyrin-fortified diet to increase butyrate in the colon were similarly protected from chemical-induced colon carcinogenesis. In addition to inhibiting HDACs, as a fatty acid, butyrate is an energy source for colon epithelial cells; however, colon cancer cells show a metabolic shift toward burning glucose for energy. Mouse colon tumors showed increased abundance of markers of glucose metabolism and concentrations of intracellular butyrate and decreased butyrate oxidation compared with adjacent normal colon cells, suggesting that butyrate was not efficiently metabolized in the cancer cells. Analysis of tissue sections revealed that tumors in high fiber-fed, B. fibrisolvens–colonized mice had greater acetylation of histone H3, expression of proapoptotic genes, and abundance of apoptotic markers than did either tumors in control mice or adjacent normal colon epithelia. In human tissue, colorectal adenocarcinomas had increased abundance of butyrate and acetylated histone H3 compared with adjacent normal mucosa. The findings show that, through bacterial fermentation in the gut and changes in cancer cell metabolism, fiber may selectively suppress the survival of colon cancer cells.

D. R. Donohoe, D. Holley, L. B. Collins, S. A. Montgomery, A. C. Whitmore, A. Hillhouse, K. P. Curry, S. W. Renner, A. Greenwalt, E. P. Ryan, V. Godfrey, M. T. Heise, D. S. Threadgill, A. Han, J. A. Swenberg, D. W. Threadgill, S. J. Bultman, A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. Cancer Discov. 4, 1387–1397 (2015). [PubMed]

C. Sebastián and R. Mostoslavsky, Untangling the fiber yarn: Butyrate feeds Warburg to suppress colorectal cancer. Cancer Discov. 4, 1368–1370 (2015). [PubMed]