Elisabeth Kelber

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.

Beeinflussung der fäkalen Gallensäureexkretion durch Fischöl bei gesunden Probanden

ZusammenfassungVerschiedene Studien weisen auf einen protektiven Effekt von Fischöl bei der Kolonkarzinomentstehung hin. Mögliche Einflüsse auf die muscosale Prostaglandin-E2-Synthese wurden hierbei als Wirkungsmechanismus beschrieben. Zusätzliche Effekte auf die fäkale Exkretion von Gallensäuren könnten ebenso von Bedeutung sein, da insbesondere sekundäre Gallensäuren als Promotoren bei der Kolontumorentstehung angesehen werden. In der vorliegenden Studie wurde bei 12 gesunden Probanden der Effekt einer täglichen Supplementierung mit 11 g Fischöl (FO) bzw. Maiskeimöl (MO) über jeweils 4 Wochen zusätzlich zu einer fettreduzierten Basiskost (30 % der Gesamtenergie als Fett) auf die fäkale Exkretion von Gallensäuren untersucht. Die Analyse des fäkalen Gallensäurenspektrums erfolgte gaschromatographisch. Die Gesamtausscheidung an Gallensäuren war unter FO nicht signifikant verschieden von derjenigen unter MO (301,9 vs. 320,3 mg/Tag). Unter FO ergab sich jedoch eine tendenziell niedrigere Exkretion der sekundären Gallensäure Lithocholsäure als unter MO (99,6 vs. 109,4 mg/Tag, p=0,22). Da sekundäre Gallensäuren als ein wesentlicher Promotor der Kolonkarzinogenese angesehen werden, sind diese Veränderungen positiv im Hinblick auf eine mögliche Kolonkarzinomprävention zu werten.SummarySeveral studies indicated a protective effect of fish oil on colon carcionogenesis 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 promotors 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 promotors of colon carcinogenesis, these findings may implicate a favorable situation with respect to colon cancer prevention.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.