There is substantial evidence that bile acids may enhance the colon tumorigenesis induced by chemical carcinogens and that agents stimulating increased bile acid excretion may show similar promoting or enhancing activity. To test the premise that these agents might modify topographical ultrastructure of the small intestine and colon in the absence of carcinogens, rats were fed for 6 weeks on chemically defined diets containing 2% levels of three commercial bile acid sequestrants or 15% levels of wheat bran, cellulose, pectin, or alfalfa. Major qualitative and quantitative deviations from normal morphology were observed with each of the three sequestrants. Similar but less dramatic modifications occurred with diets containing alfalfa or pectin, both of which either “bind” bile acids in vitro or result in increased bile acid excretion. Bran and cellulose, which neither “bind” bile acids nor increase their fecal excretion, were without significant effects on intestinal or colonic morphology. The morphological deviations observed with bile acid sequestrants were shown to be a direct response to free or bound bile acids by comparing the morphological modifications resulting from daily intracolonic infusions of free bile acids, sequestrant-bound bile acids, or the sequestrant alone.
Presented at the Workshop on Fat and Cancer, December 10 to 12, 1979, Bethesda, Md. Supported in part by USPHS Grant HL-02033, a grant from the USDA, and the Research and Development Fund of the Department of Biochemistry.