Abstract PL03-01: A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner

It is controversial whether dietary fiber protects against colorectal cancer because of conflicting results from human epidemiologic studies. However, these studies and mouse models of colorectal cancer have not controlled the composition of gut microbiota, which ferment fiber into short-chain fatty acids such as butyrate. Butyrate is noteworthy because it has energentic and epigenetic functions in colonocytes and tumor-suppressive properties in colorectal cancer cell lines. We colonized BALB/c mice with wild-type or mutant strains of a butyrate-producing bacterium in a gnotobiotic facility, provided them with high- or low-fiber diets that were otherwise identical and isocaloric, and used azoxymethane (AOM) to induce colorectal tumors. Analysis of these gnotobiotic mouse models demonstrated that fiber conferred a significant tumor-suppressive effect but in a microbiota- and butyrate-dependent manner. To confirm that butyrate is a causal factor, the anticancer chemoprotective effect was recapitulated in mice without any butyrate-producing bacteria when they were provided a tributyrin-fortified diet. Our data support a general mechanism that includes microbial fermentation of fiber rather than fiber exclusively speeding colonic transit to minimize the exposure of colonocytes to ingested carcinogens. Our data also support a molecular mechanism that is metaboloepigenetic. Normal colonocytes utilize butyrate as their primary energy source, whereas cancerous colonocytes rely on glu...

Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Donohoe, D., Holley, D., Collins, L., Montgomery, S., Whitmore, A., Curry, K., Renner, S., Greenwalt, A., Ryan, E., Godfrey, V., Threadgill, D., Swenberg, J., Threadgill, D., Bultman, S. Tags: Diet and Cancer: Oral Presentations - Invited Abstracts Source Type: research