Search

Background/aims: Dietary fiber can stimulate intestinal epithelial cell proliferation. The aim of this study was to resolve the different roles of fermentation and intraluminal viscosity on this trophic action and to investigate reported interactions between fiber and dietary fat., Methods: Conventional and germfree mice were fed guar gum in combination with low- or high-lipid diets for 2 weeks, and crypt cell production rates were determined., Results: Guar gum significantly stimulated proliferation in the small intestine, especially when combined with fat. Lipid itself also stimulated proliferation in the small intestine and had a direct trophic effect in the cecum and colon of the germfree mice. Fiber markedly stimulated proliferation in the cecum and colon but only in the conventional group. Interactions between lipid and bacteria and between guar gum and bacteria were also observed in the small intestine., Conclusions: Guar gum has a trophic effect in the small bowel, probably related to viscosity, in addition to its fermentation-related actions in the colon. Positive interaction with lipid may be associated with delayed absorption. Lipid also has its own direct actions on small bowel mucosal proliferation, which are attenuated by the presence of bacteria.

Abnormal intestinal crypt cell proliferation is considered to be an important early risk marker for colorectal cancer but measurement of the rate and spatial distribution of cell division by histochemical localization of DNA synthesis is labour-intensive and expensive. We developed and evaluated a simpler technique for measurement of these parameters using direct visual analysis of mitotic figures in microdissected crypts. The direct crypt analysis technique was applied to colorectal biopsies from patients with ulcerative colitis or no mucosal abnormality. A characteristic shift of cell division toward the intestinal lumen was detected in patients with ulcerative colitis. The direct method was validated using rats fed diets containing cellulose, or guar gum to stimulate mucosal cell proliferation. The crypt cell proliferation rate (CCPR) was measured by the metaphase-arrest technique and the results were compared with direct crypt analysis. There was a fivefold range of CCPR values at three sampling sites across the dietary groups. An excellent linear correlation between the results by the two techniques was obtained (r = 0.98; P < 0.001). In a second experiment the spatial distribution of dividing cells between five zones in colonic crypts, determined by the new method or by staining with BrdU, was compared. Good agreement was again achieved. Visual analysis of intact crypts is a valid technique for the measurement of crypt cell cytokinetics and it is particularly suited for use in a clinical environment.

The effects of saturated and polyunsaturated dietary lipids on intestinal mucosal cell proliferation were investigated in rats. Animals were randomly allocated to three groups of 10, and fed fibre-free diets containing lipid in the form of lard, corn oil or fish oil at a level of 80 g/kg. Total energy intake was kept constant by pair-feeding. After 14 days the crypt cell production rates (CCPR) at two sites in the small intestine, one site in the caecum and two sites in the colon were determined by the metaphase arrest technique, together with circulating levels of enteroglucagon and gastrin and parameters of mucosal morphology. Consumption of fish oil led to lower CCPR compared to corn oil at all sampling positions except the caecum (Treatment approximately 50% of control values; P < 0.05). In animals fed lard the CCPR in the small bowel was not significantly different to that of animals fed corn oil but their rates were lower in the colon. Post-prandial enteroglucagon and gastrin levels were lower in animals fed fish oil compared to the other two groups. These results suggest that polyunsaturated fatty acids of the n - 3 series may support a relatively low rate of crypt cell proliferation in some regions of the alimentary tract and might thereby tend to suppress the progression of colorectal neoplasms.

The effects of corn oil, guar gum and cellulose on mucosal proliferation were investigated in rats. Animals were allocated to three groups and fed a fiber-free diet or diets containing 100 g/kg of cellulose or guar gum. Each group was subdivided to receive corn oil at 40 or 80 g/kg. The crypt cell production rate (CCPR) was determined after 28 d. Consumption of guar gum or corn oil led to greater CCPR in the ileum and cecum. In a second experiment, animals were allocated to two groups and fed diets containing either cellulose or guar gum (100 g/kg). Each group was again subdivided to receive either corn oil (80 g/kg) or minimal lipid (linolenic acid, 10 g/kg). The trophic effect of guar gum occurred even in the low lipid-fed group, indicating that guar gum exerts a positive effect on cell turnover independently of any interaction with luminal lipid. However, the highest CCPR occurred in animals fed guar gum and corn oil. Postprandial enteroglucagon and gastrin concentrations were highest in animals fed both guar gum and corn oil. Thus, corn oil and guar gum exert independent trophic effects on the intestinal mucosa. The combination of effects led to a three- to four-fold increase in colon mucosal CCPR.