EFFECT OF FAT AND FIBER ON COLONIC INTESTINAL EPITHELIAL CELLS

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Colon cancer is a common human malignancy. Dietary fat and fiber have been shown to affect the incidence of colorectal cancer. Populations consuming diets high in fat and low in fiber overall have greater incidence rates of colorectal cancer, compared to populations consuming less fat and more fiber. It is not entirely clear whether dietary fat and fiber are independent variables with respect to colon carcinogenesis. Sodium butyrate, a short chain fatty acid, is generated in the colon in large quantities as dietary fiber is fermented by colonic bacteria. Sodium butyrate, in vitro, reduces the proliferation and induces apoptosis in cultured colon cancer cells. This research examines the effect of different levels of dietary fat and fiber on the proliferation and death of colonic epithelial cells. Subjects are given a well-controlled diet (weight maintaining, metabolic), with fat/fiber combination (high, normal or low fat and high, normal or low fiber) as the independent variable. Upon admission, after baseline endoscopic biopsy (by flexible sigmoidoscopy), subjects are placed on a low fat, high fiber diet for 4 wks. Assessment of colonic epithelium, sodium butyrate, and Ki-ras oncogene mutations are performed using endoscopic biopsy, blood, and stool samples. During the funding period 12/01/95 - 11/30/96 a total of 2 subjects have completed the study. Both subjects received a high fiber/low fat diet for 30 days (21.5% fat P/S ratio 1.5, 15.4% protein, 63.2% CHO, 47 g dietary fiber/2400Cal). Both subjects tolerated the study and the procedures involved without event. All subjects have had multiple colonic biopsies taken without difficulty or side effects. There are no definitive scientific results to report at this time. However, several important general conclusions can be made from these studies. First, multiple weekly flexible sigmoidoscopy examinations can be done safely in human volunteers with minimal, if any, adverse effects over 4 weeks. There are no major effects on the microscopic structure of the colonic mucosa after multiple repeated mucosal biopsies. There is early indication based on purely qualitative data on 2 subjects that high fiber in the diet affects the extent of apoptosis in the colon mucosa.