. Dietary fiber decreases colonic epithelial cell proliferation and protein synthetic rates in human subjects. Am J Physiol Endocrinol Metab 290: E1104 -E1108, 2006; doi:10.1152/ajpendo.00557.2005.-Although it has been proposed that high fiber consumption can prevent proliferative diseases of the colon, the clinical data to support this hypothesis have been inconsistent. To provide a more robust measure of the effects of fiber on colonic mucosal growth than previous studies, we evaluated both cell proliferation and colonic mucosal protein synthesis in nine healthy volunteers after they consumed a typical Western diet (Ͻ20 g fiber/day) or a Western diet supplemented with wheat bran (24 g/day) in a randomized crossover design. Biopsies taken from the sigmoid colon were used to assess mucosal proliferation by determining proliferating cell nuclear antigen (PCNA) in crypt cells and to assess mucosal protein synthetic rate using stable isotopically labeled leucine infusion. Fiber supplementation produced a 12% decrease in labeling index (%crypt cells stained with PCNA) (P Ͻ 0.001) and an 11% decrease in mucosal protein fractional synthetic rate (FSR; P Ͻ 0.05). Moreover, mucosal protein FSR correlated directly with labeling index (r 2 ϭ 0.22, P Ͻ 0.05). These data demonstrate that increased wheat bran consumption decreases colonic mucosal proliferation and support the potential importance of dietary fiber in preventing proliferative diseases of the colon. metabolism; cancer; short-chain fatty acids MORE THAN 35 YEARS AGO, Burkitt (6) hypothesized that dietary fiber can prevent proliferative diseases of the colon, such as colorectal cancer and polyposis syndromes. However, the effect of fiber intake on colonic disease is unclear because of conflicting results from different cross-sectional epidemiologic studies, longitudinal cohort studies, and randomized controlled trials (30,14). In addition, data from studies that evaluated colonocyte proliferation, a presumed marker of colorectal polyp and cancer risk, found dietary fiber or its metabolites [i.e., short-chain fatty acids (SCFAs)] increased (7,8,19,23), decreased (1, 10, 17), or did not change proliferation rates (2, 9).Several factors have been proposed to explain the inconsistent relationship reported between fiber intake and colonic disease, including heterogeneity of dietary fiber, use of inadequate amounts of fiber to affect cellular metabolism, genetic differences in risk of polyps or colon cancer in study subjects, and limitations in the accuracy and precision of techniques used to measure colonocyte proliferation (14,15,32). Therefore, additional studies that address the limitations of previous investigations are needed to evaluate the effect of fiber on colon proliferation and metabolism. This issue has considerable physiological and clinical importance because of the notion that a typical Western diet, which contains Ͻ15 g/day of nonstarch polysaccharides, is considered inadequate for optimal for colonic health (15, 16).The purpose of the present study wa...