Volatile fatty acids (VFA) are produced when dietary or endogenous constituents are fermented by microbes in the colon. Some dietary fibers stimulate VFA formation. VFA have been shown to influence differentiation and proliferation of normal and malignant colinic mucosal cells, and it has been postulated that VFA may also influence the pH of the colon, and colonic function. Each of these factors appears to influence the risk of colonic carcinogenesis. Since the appropriate specimens which are needed to study the interactions of dietary fiber, VFA and colonic cell biology cannot be acquired from healthy humans, we have developed the pig as an appropriate animal model. In this study, we postulate that VFA production in the gut can be altered by feeding different dietary fibers, and that the fibers may also influence absorption of VFA into the colonic mucosal cells and blood. We further postulate that the biology of the mucosal cells will be influenced by the quantity of VFA which are absorbed, and that the lumenal environment will also be affected. To test our hypothesis, pigs will be fed diets containing purified or semi-purified fibers which are selected to show a range in solubility, physical properties and fermentability. To determine the influence of these fibers on VFA production, absorption and excretion, VFA will be measured in cecal contents, portal blood and feces. To determine the influence on cell biology, cecal and colonic biopsy specimens will be examined for cell proliferation and differentiation. The relationships of dietary fiber, VFA production and absorption, colonic cell biology and the lumenal environment of the colon will be determined so that we can more accurately select fibers which are likely to offer protection against colonic disease. This study is designed to provide data which will identify the specific effects that fibers have on the colonic environment and on the colonic cell biology of a healthy animal. From these data we may understand why there are often conflicting reports on the effect of a fiber on tumorigenesis, and we can then go on to further examine those fibers which are most likely to protect the colon against cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040845-03
Application #
3181156
Study Section
(SRC)
Project Start
1985-09-01
Project End
1990-08-31
Budget Start
1987-09-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Type
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704