Abstract 5431: Effects of various dietary fibers on intestinal carcinogenesis in Min mice

Abstract

Abstract Colorectal cancer is among the most prevalent types of cancers and its development has been associated with components in the diet. Dietary fibers seem to display a protective role, and in the search for what mechanisms may be involved increased focus has been directed at the effect of fibers on the gut micro flora. This project has included studies aimed at generating new knowledge about how various types of dietary fibers influence the intestinal tumorigenesis, inflammatory status, composition of bacteria in various intestinal segments and the interrelationships between these factors. Three different fibers were tested; a finely ground cellulose preparate, inulin and mask (a dried and finely milled brewers spent grain). All fibers were present in the diet in a lower and a higher concentration (5 % and 15%). The test diets were given to multiple intestinal neoplasia (Min) and wild type (Wt) mice from weaning until euthanation at week 11. The Min mice carry the same mutation as seen in the human familial adenomatous polyposis (FAP) syndrome that results in spontaneous development of colorectal tumors. The majority of sporadic human colorectal tumors are also mutated in the same signaling pathway. Colon carcinogenesis was induced by two subcutaneous injections of azoxymethan (day 7 ±1 and14 ±1 after birth). At euthanation a blood sample from the hepatic portal vein was obtained and the small (Min mice) and large intestine (Min and Wt mice) were removed and fixed. The coecum and spleen were weighed and snap frozen. Individual weights and diet consumption were recorded. Scoring of tumors in the small and large intestine displayed a weak but significant difference in tumor development between the different diet groups. The inulin 5% diet resulted in reduced tumor number compared to the cellulose (small and large intestine) and the mask (large intestine) fibers. Analysis by Multiplex of a large range of inflammatory cytokines in plasma revealed the presence of individual animals with high levels of certain cytokines. This variation seems to be independent of fiber type in the diet. However, analysis of several data from the individual animals with respect to any correlation between cancer development and cytokine level is presently under evaluation. Furthermore, a pilot screening of the micro flora in feces from selected representative animals demonstrated interesting differences in species variation when related to the various fibers tested and the two different doses included. All animal recordings in this study are done on the individual level; correlations between tumor development, inflammatory status and intestinal micro flora will therefore be made at several levels. In summary, our results demonstrate that various types of fibers influence the development of tumors to various degrees. Further evaluation of the data is in progress and may reveal associations between tumor development, inflammatory status and the intestinal micro flora. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5431. doi:1538-7445.AM2012-5431