Comparisons of the anti-proliferative effects of butyrate and aspirin on human colonic mucosa in vitro.

The short-chain fatty acid butyrate is regarded as a regulative agent in haemostasis of mucosal cell turnover. Inhibition of prostaglandin E2 synthesis is particularly involved in this regulation process. In the present study, proliferation was stimulated in colonic biopsies of 12 healthy subjects (age 51.3 years, range 25-81) by incubation with deoxycholic acid (5 micromol/l DCA). The anti-proliferative and cyclo-oxygenase-inhibiting properties of butyrate (10 mmol/l BUT) and of aspirin (555 micromol/l ASA) were investigated. Colonic cell proliferation was determined by bromodeoxyuridine immunohistochemistry. PGE2 release into the incubation medium was measured by radioimmunoassay. Incubation with DCA/ASA, DCA/BUT and DCA/ASA/BUT revealed a significant reduction in crypt cell proliferation as measured by the labelling index of the whole crypt in comparison to incubation with DCA alone (DCA/ASA: 0.14, P < 0.01; DCA/BUT: 0.15, P < 0.05; DCA/ASA/BUT: 0.15, P < 0.05, versus DCA: 0.18). The labelling index for the upper 40% of the crypt was only lower after incubation with DCA/ASA (0.023) compared to DCA (0.028) (P < 0.05). PGE2 release from biopsy specimens was only significantly decreased in the incubation media where ASA was added (DCA/ASA: 29.0 pg/mg mucosa/h, P < 0.005; DCA/ASA/BUT: 31.4 pg/mg mucosa/h, P < 0.01 versus DCA: 56.9 pg/mg mucosa/h). Butyrate and aspirin showed no synergistic effects. The results indicate a normalization of DCA-induced hyperproliferation of colonic mucosa by butyrate, and, even more efficiently, by aspirin. The data support the hypothesis that butyrate and aspirin can act as chemopreventive agents in colon carcinogenesis.

Effect of dietary fish oil on fecal bile acid and neutral sterol excretion in healthy volunteers.

Diet-induced increases in fecal excretion of secondary bile acids (deoxy- and lithocholic acid) and certain neutral sterols (4-cholesten-3-one and 5a-cholestan-3-one) play a role in colon cancer development, whereas dietary fish oil (FO) has been implicated as a protective agent. In the present study the effects of FO and corn oil (CO) on these fecal parameters were investigated in 12 healthy volunteers consuming a low fat (30% of energy) controlled basal diet. After 4 weeks of FO supplementation (4.4 g omega-3 fatty acids/day), daily excretion of lithocholic acid showed a trend to lower values compared to CO consumption (p = 0.2), whereas other bile acids were not different during both study periods. Daily excretion of the putative colon carcinogen 4-cholesten-3-one was significantly lower in the FO compared to the CO period. This may be another biochemical mechanism by which FO exerts its protective effect on colon cancer development.

Bile acid metabolism by colonic bacteria in continuous culture: effects of starch and pH.

Secondary bile acids (BA) have been shown to be involved as a promoting agent in the adenoma-carcinoma sequence of colorectal cancer. In previous studies, fermentation of starch has been shown to inhibit the degradation of primary to secondary BA by the colonic microflora. This study was designed to investigate BA metabolism in continuous cultures of mixed fecal bacteria to get further insights into the mechanisms of this inhibition. Fermentation vessels were fed with media containing cholic (0.6 g/l) and chenodeoxycholic acid (0.4 g/l). Cultures were either starch-free or enriched with starch (10 g/l). pH was controlled and adjusted to 7.0 or 6.0. Total culture duration was 28 days and concentrations of BA, short-chain fatty acids (SCFA), and starch were measured periodically. At pH 6, significantly more primary BA remained in the media and less secondary BA were produced. Total BA concentrations were lower at pH7. SCFA concentrations were higher in the vessels supplemented with starch. Starch was completely fermented and not present in significant amounts in any fermentation vial after the first week. These data indicate that bacterial breakdown of primary to secondary BA is inhibited when starch is simultaneously fermented. This effect can be explained by the reduction of pH resulting from SCFA production. Considering these findings, resistant starch which escapes assimilation in the small bowel may be a protective factor against colorectal cancer.

Effects of fish oil on fecal bacterial enzymes and steroid excretion in healthy volunteers: implications for colon cancer prevention.

Diet-induced changes in fecal excretion of secondary bile acids, certain neutral sterols, and bacterial enzyme activities are known to play a role in colon cancer development. Dietary fish oil (FO) has been implicated as a protective agent in colon carcinogenesis. In the present study, the effects of FO and corn oil (CO) on these fecal parameters were investigated in 24 healthy volunteers consuming a low- or a high-fat diet (30% or 50% of energy derived from fat). After four weeks of FO or CO supplementation (4.4 g of n-3 fatty acids/day), no significant differences were noted for fecal activities of beta-glucuronidase, beta-glucosidase, and sulfatase, nor was fecal bile acid excretion significantly affected by FO or CO consumption. However, daily excretion of the putative colon carcinogen 4-cholesten-3-one was significantly lower in the FO than in the CO period during low- and high-fat experiments. This may be another biochemical mechanism by which FO exerts its protective effect on colon cancer development.

[Modification of fecal bile acid excretion by fish oil in healthy probands]. / Beeinflussung der fäkalen Gallensäureexkretion durch Fischöl bei gesunden Probanden.

Several studies indicated a protective effect of fish oil on colon carcinogenesis which might be due to alterations in prostaglandin E2 synthesis of the colonic mucosa. Additional effects on fecal bile acid excretion may also play a role since especially secondary bile acids are known to act as promoters in colon cancer development. In the present study possible influences on bile acid excretion were investigated in 12 healthy volunteers whose daily diet was supplemented for 4 weeks with 11 g of fish oil (FO) and corn oil (CO) per day, respectively. Fecal bile acids were analyzed by gas-liquid-chromatography. Fecal excretion of total bile acids was not different during the periods of FO and CO-supplementation (301.9 vs. 320.3 mg/day). However, a non-significant trend to a lower daily excretion of the secondary bile acid lithocholic acid was found after FO compared to CO-ingestion (99.6 vs. 109.4 mg/day; p = 0.22). Since secondary bile acids are known promoters of colon carcinogenesis, these findings may implicate a favorable situation with respect to colon cancer prevention.

Does yogurt enriched with Bifidobacterium longum affect colonic microbiology and fecal metabolites in health subjects?

Diet-induced changes in the colonic microflora seem to play a role in colon carcinogenesis. In this study the effects of a yogurt (500 mL/d for 3 wk) enriched with Bifidobacterium longum and 5 g lactulose/L (A) on the fecal bacterial flora and various risk indexes for colon carcinogenesis were tested in 12 healthy volunteers and compared with a conventional yogurt (B). Increased excretion of bifidobacteria (P < 0.017) was found after consumption of both yogurts compared with the prestudy periods, whereas cultural counts of aerobes and anaerobes were not different. Breath-hydrogen exhalation was elevated and mouth-to-cecum transit time was accelerated in the period of yogurt A ingestion (P < 0.05) whereas no differences were found for oral-anal mean transit time, stool weight and pH, and fecal concentrations of short-chain fatty acids, bile acids, and neutral sterols. The results generally indicate great stability of the human fecal flora to this kind of dietary intervention.