Effect of cereal fibre source and processing on rectal epithelial cell proliferation

Abstract

Background-Low fat and wheat bran interventions significantly reduced the growth of small to large adenomas and modestly suppressed rectal epithelial cell proliferation in the Australian Polyp Prevention Project. Aim-To study the eVect of unprocessed wheat bran, unprocessed oat bran and processed wheat bran (Kellogg's All Bran) on rectal epithelial cell proliferation. Patients-Twenty subjects with recent adenomas and a high fat background diet were recruited. Methods-Rectal biopsy specimens were taken at entry and at the end of three sixweek periods of oat bran (64 g/day), wheat bran (25 g/day) and All Bran (38 g/day), all in association with a diet <25% energy as fat, in a randomised cross-over trial. Each of the bran supplements had a total of 11 g dietary fibre. The biopsy specimens were fixed in methacarn and stained immunohistochemically for presence of the proliferating cell nuclear antigen (PCNA). The kinetics used to measure proliferation were labelling index, whole distribution of labelled cells, and labelled cells in the top two-fifths of crypts using analysis of variance. Results-There were no significant diVerences in mean labelling indexes between the four diets or in the percentage of labelled cells in the top two-fifths (p=0.59), but activity in the top two-fifths of crypts was lowest with wheat bran. The mean (SD) labelling indexes were 2.23 (0.11)% for control, 2.13 (0.08)% for wheat bran, 2.19 (0.09)% for oat bran, and 2.12 (0.08)% for All Bran. The proportion in the top two-fifths of the crypts was 2.6 (0.6)% for control, 2.15 (0.5)% for wheat bran, 3.3 (0.9)% for oat bran, and 3.1 (0.9)% for All Bran. On analysis of whole distribution, there was no significant overall eVect of diets but there was a diVerence between subjects. Analysis including total fibre intake also did not identify eVects on proliferation. Conclusion-In this study of high risk subjects with initial high fat diets, dietary fibre in association with a low fat diet had no eVect on rectal epithelial cell proliferation, although wheat bran had the greatest eVect on percentage of labelled cells in the top two-fifths of crypts.

Diet and cancer: assessing the risk

“…Such studies have provided conflicting data on the effect of high calcium and fibre intakes on hyperproliferation. (Van Munster et al 1994;Alberts et al 1997;Macrae et al 1997;Holt et al 1998). Although whole crypt microdissection and mitosis counting has been shown to be a reliable, reproducible and robust technique for assessing crypt cell proliferative state (CCPS) in the human colon, the precise relation of an increased CCPS to the neoplastic process remains uncertain (Mills et al 2001).…”

Dietary fiber decreases colonic epithelial cell proliferation and protein synthetic rates in human subjects

“…However, the results from studies evaluating the effect of dietary fiber or SCFA administration on colorectal neoplasia or colonocyte proliferation are not conclusive because of inconsistent results from different studies (1,4,9,21,22,30). This is the first study to evaluate the effect of dietary fiber on colonic mucosal proliferation and protein metabolism in healthy human subjects.…”

“…This approach requires fresh tissue and only labels the S phase of the cell cycle (28). In the present study, we evaluated cell proliferation by staining colonic tissue for PCNA, which has the advantages of labeling all phases of the cell cycle, and by using fixed, rather than fresh, tissue (22). In addition, this approach is associated with minimal interobserver variability (20,22,31).…”

“…In the present study, we evaluated cell proliferation by staining colonic tissue for PCNA, which has the advantages of labeling all phases of the cell cycle, and by using fixed, rather than fresh, tissue (22). In addition, this approach is associated with minimal interobserver variability (20,22,31). We also evaluated the rate of protein synthesis in colonic tissue by using stable isotopically labeled tracer infusion to provide an additional and independent marker of cellular metabolism that is associated with proliferation.…”

“…Wheat bran was used as a source of fiber, because it results in high intraluminal concentrations of butyrate, which is the preferred fuel of colonic epithelia. In addition, we used two independent measures to assess cell growth: 1) immunohistochemistry to determine crypt proliferating cell nuclear antigen (PCNA) content, which provides an index of cell proliferation, and 2) stable isotopically labeled tracer infusion to determine mucosal protein synthetic rates (11,22). We hypothesized that increasing dietary fiber would cause a decrease in rates of mucosal cell proliferation and protein synthesis.…”