Fecal Bile Acid Concentrations Research Articles

Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes

Bile acids are recognized as metabolic modulators. The present study was aimed at evaluating the effects of a potent Asbt inhibitor (264W94), which blocks intestinal absorption of bile acids, on glucose homeostasis in Zucker Diabetic Fatty (ZDF) rats. Oral administration of 264W94 for two wk increased fecal bile acid concentrations and elevated non-fasting plasma total Glp-1. Treatment of 264W94 significantly decreased HbA1c and glucose, and prevented the drop of insulin levels typical of ZDF rats in a dose-dependent manner. An oral glucose tolerance test revealed up to two-fold increase in plasma total Glp-1 and three-fold increase in insulin in 264W94 treated ZDF rats at doses sufficient to achieve glycemic control. Tissue mRNA analysis indicated a decrease in farnesoid X receptor (Fxr) activation in small intestines and the liver but co-administration of a Fxr agonist (GW4064) did not attenuate 264W94 induced glucose lowering effects. In summary, our results demonstrate that inhibition of Asbt increases bile acids in the distal intestine, promotes Glp-1 release and may offer a new therapeutic strategy for type 2 diabetes mellitus.

Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet

BackgroundThe hypocholesterolemic effects of lactic acid bacteria (LAB) have now become an area of great interest and controversy for many scientists. In this study, we evaluated the effects of Lactobacillus plantarum 9-41-A and Lactobacillus fermentum M1-16 on body weight, lipid metabolism and intestinal microflora of rats fed a high-cholesterol diet.MethodsForty rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The LAB-treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum 9-41-A or Lactobacillus fermentum M1-16. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat pad weights, serum and liver cholesterol and lipid levels, and fecal cholesterol and bile acid concentrations were measured. Liver lipid deposition and adipocyte size were evaluated histologically.ResultsCompared with rats fed a high-cholesterol diet but without LAB supplementation, serum total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in LAB-treated rats (p < 0.05), with no significant change in high-density lipoprotein cholesterol levels. Hepatic cholesterol and triglyceride levels and liver lipid deposition were significantly decreased in the LAB-treated groups (p < 0.05). Accordingly, both fecal cholesterol and bile acids levels were significantly increased after LAB administration (p < 0.05). Intestinal Lactobacillus and Bifidobacterium colonies were increased while Escherichia coli colonies were decreased in the LAB-treated groups. Fecal water content was higher in the LAB-treated groups. Compared with rats fed a high-cholesterol diet, administration of Lactobacillus plantarum 9-41-A resulted in decreases in the body weight gain, liver and fat pad weight, and adipocytes size (p < 0.05).ConclusionsThis study suggests that LAB supplementation has hypocholesterolemic effects in rats fed a high-cholesterol diet. The ability to lower serum cholesterol varies among LAB strains. Our strains might be able to improve the intestinal microbial balance and potentially improve intestinal transit time. Although the mechanism is largely unknown, L. plantarum 9-41-A may play a role in fat metabolism.

Abstract A121: Genetic variation in CYP7A1, bile acids, and risk of adenoma in the proximal colon

Abstract Background: Secondary bile acids, specifically deoxycholic acid (DCA), are probable carcinogens of colorectal cancer, particularly for lesions arising in the proximal colon. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the conversion of cholesterol to primary bile acids in the liver. Genetic variation in CYP7A1 has been reported to modify risk of colorectal neopolasia arising in the proximal colon. Methods: Using the placebo arm of our ursodeoxycholic acid chemoprevention trial, we studied the relationships between baseline fecal bile acid concentrations, six allelic variants in CYP7A1, and risk of proximal adenomas after three years of follow-up (n = 253). Because bile acid levels are strongly influenced by sex, we considered gender as a potential effect modifier. After testing four possible modes of inheritance for associations between genetic polymorphisms and proximal adenoma, we present results generated under log-additive models. Results: The relationship between fecal DCA levels and development of proximal adenoma was strongly modified by gender (pinteraction &amp;lt; 0.001). Compared with the lowest quintile, higher levels of DCA were associated with significantly increased odds of proximal adenoma in men (OR = 7.14; 95% CI = 2.07 to 24.6) but non-significantly decreased odds in women (OR = 0.39, 95% CI = 0.13 to 1.20). These associations were slightly attenuated for men (OR = 5.82; 95% CI = 1.65 to 20.5) and women (OR = 0.44, 95% CI = 0.14 to 0.43) after adjusting for age and body mass index. In addition, analyses of two linked CYP7A1 SNPs (D′ = 0.75 and r2 = 0.5) showed that carriage of the minor allele for rs8192871 and rs13251096 lowered the odds of proximal adenoma by 45% (OR = 0.55; 95% CI = 0.36 to 0.85) and 41% (OR = 0.59, 95% CI = 0.40 to 0.89), respectively. Furthermore, these two SNPs were associated with DCA, such that carriers of two minor alleles had significantly lower fecal DCA levels (Kruskal-Wallis p = 0.003 for both SNPs). None of the other four CYP7A1 SNPs showed any association with proximal adenoma or fecal bile acid levels. Conclusions: In this study population, CYP7A1 polymorphisms are significantly associated with risk of adenoma in the proximal colon, likely through their effects on bile acid levels. Sex, age, body mass index, and other factors that influence bile acid levels may further affect this risk. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A121.

Effects of Dietary Fish Protein on Serum and Liver Lipid Concentrations in Rats and the Expression of Hepatic Genes Involved in Lipid Metabolism

Dietary proteins influence the lipid metabolism of human subjects and animals. This study evaluated the effects of fish protein on lipid metabolism in rats. Alaska pollock fillets, widely supplied as raw materials of surimi, were used as fish protein. As parameters of lipid metabolism, cholesterol and triacylglycerol concentrations in the serum and liver, the fecal excretion of bile acids, and the hepatic expression of genes encoding proteins involved in lipid homeostasis were examined. Rats fed fish protein showed decreased cholesterol concentrations in the serum and liver, and fecal bile acid and cholesterol concentrations were increased. This was caused by the increased expression of cholesterol 7alpha-hydroxylase (CYP7A1) as the digested fish protein inhibited the absorption of bile acid and cholesterol in the small intestine. In addition, it was found that dietary fish protein affects the farnesoid X receptor/small heterodimer partner-dependent pathway, which is negatively regulated by the decreased reabsorption of bile acid. Furthermore, it increased the binding to the promoter of CYP7A1 through activated liver receptor homologue-1.

Physical Activity as a Determinant of Fecal Bile Acid Levels

Physical activity is protective against colon cancer, whereas colonic bile acid exposure is a suspected risk factor. Although likely related, the association between physical activity and bile acid levels has not been well-studied. Furthermore, the effect of triglycerides, which are known to modify bile acid levels, on this relationship has not been investigated. We conducted a cross-sectional analysis of baseline fecal bile acid levels for 735 colorectal adenoma formers obtained from participants in a phase III ursodeoxycholic acid chemoprevention trial. Compared with the lowest quartile of recreational physical activity duration, the highest quartile was associated with a 17% lower fecal bile acid concentration, adjusted for age, sex, dietary fiber intake, and body mass index (P = 0.042). Furthermore, consistent with a previously established relationship between serum triglyceride levels and bile acid metabolism, we stratified by triglyceride level and observed a 34% lower fecal bile acid concentration (highest versus lowest quartiles of physical activity) in individuals with low triglycerides (<136 mg/dL; P = 0.002). In contrast, no association between physical activity and fecal bile acid concentration was observed for subjects with high triglycerides (> or =136 mg/dL). Our results suggest that the biological mechanism responsible for the protective effect of physical activity on the incidence of colon cancer may be partially mediated by decreasing colonic bile acid exposure. However, this effect may be limited to individuals with lower triglyceride levels.

Karaya root saponin exerts a hypocholesterolemic response in rats fed a high-cholesterol diet

Different sources of saponins are known to have hypocholesterolemic activity with varying degrees of efficacy. We hypothesize that karaya root saponin would efficiently reduce cholesterol. The aim of this study is to examine the comparative hypocholesterolemic effect of karaya root saponin in rats fed a high-cholesterol diet. Sixty male Wister-Imamichi rats were divided into 5 groups of 12 rats each constituting of the following: control group, soybean saponin-supplemented group, karaya root saponin-supplemented group, quillaja saponin-supplemented group, and tea saponin-supplemented group. Compared with the control diet, both the karaya root- and quillaja saponin-supplemented diets significantly reduced (P < .05) serum cholesterol and atherogenic index. Karaya root saponin significantly increased the serum high-density lipoprotein cholesterol, high-density lipoprotein cholesterol/cholesterol ratio, and fecal cholesterol concentrations (P < .05). The triacylglycerol concentration was significantly reduced only in the quillaja saponin-supplemented rats (P < .05). All the tea, soybean, karaya root, and quillaja saponins significantly reduced low-density lipoprotein cholesterol, and the greatest reduction was observed with karaya root saponin. Highest fecal bile acid concentration was found with quillaja saponin, whereas highest liver bile acid concentration was observed with karaya root saponin-supplemented rats (P < .05). These results collectively suggest that karaya root saponin can efficiently reduce serum cholesterol concentration in rats.

Investigations on the Effect of Flavonoids from Banana, Musa Paradisiaca L. on Lipid Metabolism in Rats

Oral administration of flavonoids extracted from unripe fruits of Musa paradisiaca showed significant hypolipidemic activities in male rats (Sprague Dawley strain) at a dose of 1 mg/100 g body weight (BW)/day. Concentrations of cholesterol, phospholipids, free fatty acids, and triglycerides showed significant decrease in the serum, liver, kidney, and brain of experimental animals. HMG CoA reductase activity was found to be enhanced, while activities of glucose-6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Activities of lipoprotein lipase and plasma LCAT showed significant enhancement. A significant increase in the concentrations of hepatic and fecal bile acids and fecal neutral sterols was also observed indicating a higher rate of degradation of cholesterol. The present study indicates that although there is an increase in the rate of synthesis of cholesterol in the liver, the process of degradation exceeds the rate of synthesis.

Fecal Sterol and Bile Acid Biomarkers: Runoff Concentrations in Animal Waste-Amended Pastures

Nonpoint source pollution is the leading remaining cause of water quality problems. The extent of NPS pollution is often more difficult or expensive to monitor at the point(s) of origin, as compared to monitoring of point sources. This study evaluated the hypothesis that animal manure (chicken, cow, horse, and pig) applied to pasture contribute fecal sterols and bile acids to runoff. The study also assessed the potential benefit of fecal sterols and bile acids as biomarkers in distinguishing fecal pollution and its sources. Fecal sterol and bile acid concentrations were determined in flow-weighted composite runoff samples collected from 2.4 × 6.1 m plots (n = 3) amended with manure. Runoff was generated from simulated rainfall (152 mm.h−1). Runoff samples from manure-amended plots showed high concentrations of fecal sterol (ranged from 13 ± 1 to 1,287 ± 183) and bile acid (ranged from 24 ± 1 to 2,251 ± 248) biomarkers. The profiles of fecal sterols and bile acids in runoff samples were similar to those of fresh manure for all selected animals. For runoff and fresh manure, chenodeoxycholic acid, deoxycholic acid, epicoprostanol, and hyodeoxycholic acid were consistent biomarkers for chicken, cow, horse, and pig, respectively, suggesting that sterols and bile acids can be used to identify sources and occurrence of fecal matter in water and sediments.

Use of Sterol and Bile Acid Biomarkers to Identify Domesticated Animal Sources of Fecal Pollution

The objective of this study was to demonstrate the use of chemical biomarkers (fecal sterols and bile acids) to identify selected sources of fecal pollution in the environment. Fecal sterols and bile acids were determined for pig, horse, cow, and chicken feces. Ten to twenty-six fresh fecal samples were collected for each animal, and the concentrations of fecal sterols (coprostanol, epicoprostanol, cholesterol, cholestanol, stigmastanol, and stigmasterol) and bile acids (lithocholic acid, deoxycholic acid, cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, hyodeoxycholic acid) were determined using a gas chromatography and mass spectrometer (GC-MS) technique. Correlation study was performed among sterol and bile acid variables for selected animals, and a ratio (cholesterol + epicoprostanol)/(deoxycholic acid + chenodeoxycholic acid + hyodeoxycholic acid) has been proposed as an indicator for assessing fecal input. The levels of (cholesterol + epicoprostanol)/(deoxycholic acid + chenodeoxycholic acid + hyodeoxycholic acid) in horse, cow, chicken and pig were observed 3.258 ± 1.191, 1.921 ± 1.006, 1.013 ± 0.726, and 0.205 ± 0.119 respectively and the ratio of horse: cow: chicken: pig was 16: 9: 5: 1. This ratio suggests the potential of sterol and bile acid biomarkers in identifying sources and occurrence of fecal matter. While additional work using polluted water (as opposed to fresh fecal samples) as well as multiple pollution sources are needed to investigate the transport of these biomarkers into water bodies.

Use of selected chemical markers in combination with a multiple regression model to assess the contribution of domesticated animal sources of fecal pollution in the environment

Human and animal wastes are major sources of environmental pollution. Reliable methods of identifying waste sources are necessary to specify the types and locations of measures that best prevent and mitigate pollution. This investigation demonstrates the use of chemical markers (fecal sterols and bile acids) to identify selected sources of fecal pollution in the environment. Fecal sterols and bile acids were determined for pig, horse, cow, and chicken feces (10–26 feces samples for each animal). Concentrations of major fecal sterols (coprostanol, epicoprostanol, cholesterol, cholestanol, stigmastanol, and stigmasterol) and bile acids (lithocholic acid, deoxycholic acid, cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and hyodeoxycholic acid) were determined using a gas chromatography and mass spectrometer (GC–MS) technique. The fecal sterol and bile acid concentration data were used to estimate parameters of a multiple linear regression model for fecal source identification. The regression model was calibrated using 75% of the available data validated against the remaining 25% of the data points in a jackknife process that was repeated 15 times. The regression results were very favorable in the validation data set, with an overall coefficient of determination between predicted and actual fecal source of 0.971. To check the potential of the proposed model, it was applied on a set of simulated runoff data in predicting the specific animal sources. Almost 100% accuracy was obtained between the actual and predicted fecal sources. While additional work using polluted water (as opposed to fresh fecal samples) as well as multiple pollution sources are needed, results of this study clearly indicate the potential of this model to be useful in identifying the individual sources of fecal pollution.

Effects of a synbiotic milk product on human intestinal ecosystem

To investigate the effect of prolonged consumption of a synbiotic milk (Synbiotic) containing Lactobacillus acidophilus (strain 74-2, 10(7) CFU ml(-1)), Bifidobacterium lactis (strain 420, 10(7) CFU ml(-1)) and 2% inulin on colonic ecosystem in healthy humans. A group of 26 healthy subjects, aged 22-47 years, participated in a 6-week placebo-controlled dietary intervention study. After a 2-week baseline period, in which all volunteers consumed 500 ml day(-1) of 2% skimmed milk (Placebo), the study was designed as a randomized, double-blind, two-armed parallel study in which 4-week consumption of 500 ml day portions of Synbiotic or Placebo were compared. Faecal microbial counts, pH, l-lactic acid and bile acid concentrations were assessed before and after the intervention. Synbiotic consumption significantly decreased faecal dry weight (P < 0.01) and l-lactic acid (P < 0.05) concentration, while significantly increased faecal bifidobacteria (P < 0.05) and lactobacilli (P < 0.01) counts. The tested synbiotic milk showed its synbiotic nature by enhancing the growth of bifidobacteria and lactobacilli. Scientific support to functional effect of a synbiotic milk.

Fasting plasma bile acid concentrations in Asian vegetarians, Caucasian vegetarians and Caucasian omnivores

PurposeDifferences in faecal bile acid excretion have been reported between vegetarians and meat‐eaters. The purpose of this study is to compare fasting plasma bile acid concentrations in Asian vegetarians, white vegetarians and white meat‐eaters.Design/methodology/approachA human experimental study comparing fasting plasma bile acid concentrations in Asian vegetarians, white vegetarians and white meateaters. Three groups of premenopausal women have been recruited: Caucasian omnivores (n = 19), Caucasian Vegetarians (n = 16) and Asian vegetarians (n = 17). Fasting plasma bile acid concentrations were determined by gas‐liquid chromatography.FindingsAlthough faecal bile acid concentrations were lower in the Caucasian vegetarians than in the omnivores, fasting plasma bile acid concentrations did not differ.Originality/valueThe present results indicate that fasting levels of plasma bile acids in premenopausal women do not necessarily reflect faecal bile acid concentrations.

Experimental colorectal cancer: the relationship of diet and faecal bile acid concentration to tumour induction.

Epidemiological studies have consistently suggested an aetiological relationship between certain dietary constituents, faecal bile acid (FBA) concentration and colorectal cancer. This study was designed to examine the effect of the dietary manipulation of fat and fibre on tumour induction and on various faecal characteristics in Albino Swiss rats. A total of 232 animals were maintained on one of four different diets for 4, 20 and 28 weeks respectively. The diets were classified as high fat high fibre, low fat high fibre, high fat low fibre and low fat low fibre. The groups were further sub-divided according to the administration of systemic azoxymethane (10 mg/kg per week) or saline over 12 consecutive weeks. The high fat low fibre diet was associated with the highest risk for tumour production and the low fat high fibre diet with the lowest risk. Statistically significant differences between all the diets were noted with the exception of a comparison between the high fat high fibre and low fat high fibre diets. The highest total concentration of free FBA was found in the faeces from animals fed low fibre containing diets. The results show a clear influence of both fat and fibre on tumour induction while, in this model, fibre was the principle determinant of faecal bile acid concentration.

Unconjugated faecal bile acids in familial adenomatous polyposis analysed by gas-liquid chromatography and mass spectrometry.

Previous studies have suggested reduced formation of secondary bile acids in patients with familial adenomatous polyposis (FAP). Developments in the collection, extraction and analysis of faecal bile acids as well as in the accurate diagnosis of FAP by DNA markers prompted reinvestigation of this hypothesis. The median (interquartile range (i.q.r.)) faecal bile acid concentration (3.69 (1.66-5.36) mumol per g dry weight) and daily excretion rate (60.5 (29-149) mumol per g per 24 h) in ten patients with FAP were similar to those of nine control subjects (3.31 (0.65-8.38) mumol per g dry weight and 30.1 (7.9-228) mumol per g per 24 h). Although the median (i.q.r.) concentration of only one bile acid (12-oxo-lithocholic acid) was significantly different between patients with FAP and controls (49 (34-70) versus 0 (0-20) nmol per g dry weight, P = 0.006), the derivatives of chenodeoxycholic acid (3.35 (1.76-5.32) versus 0.51 (0.13-2.37) mumol per g dry weight, P = 0.02) and cholic acid (1.63 (0.42-2.34) versus 0.80 (0.13-3.57) mumol per g dry weight, P = 0.006) were increased in those with polyposis. These results show increased bacterial biotransformation of faecal bile acids in patients with FAP.

Adzuki resistant starch lowered serum cholesterol and hepatic 3-hydroxy-3-methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7α-hydroxylase mRNA levels in rats fed a cholesterol diet

We examined the effects of adzuki bean resistant starch on serum cholesterol and hepatic mRNA in rats fed a cholesterol diet. The mRNA coded for key regulatory proteins of cholesterol metabolism. The control rats were fed 15 % cornstarch (basal diet, BD). The experimental rats were fed BD plus a 0.5 % cholesterol diet (CD), or a 15 % adzuki resistant starch plus 0.5 % cholesterol diet (ACD) for 4 weeks. The serum total cholesterol and VLDL + intermediate density lipoprotein + LDL-cholesterol levels in the ACD group were significantly lower than those in the CD group throughout the feeding period. The total hepatic cholesterol concentrations in the CD and ACD groups were not significantly different. The faecal total bile acid concentration in the ACD group was significantly higher than that in the BD and CD groups. Total SCFA and acetic acid concentrations in the ACD group were significantly higher than those in the CD group but there were no significant differences in the concentrations between the ACD and BD groups. The hepatic LDL-receptor mRNA and cholesterol 7alpha-hydroxylase mRNA levels in the ACD group were significantly higher than those in the CD group and the hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase mRNA level in the ACD group was significantly lower than in the CD group. The results suggest that adzuki resistant starch has a serum cholesterol-lowering function via enhancement of the hepatic LDL-receptor mRNA and cholesterol 7alpha-hydroxylase mRNA levels and faecal bile acid excretion, and a decrease in the hepatic HMG-CoA reductase mRNA level, when it is added to a cholesterol diet.

Effect of Dried Plums on Colon Cancer Risk Factors in Rats

: Dried plums (that is, prunes) are a fruit that show promise as a food to lower colon cancer risk, based on their high content of dietary fiber and polyphenolics. In this study, we have examined the effect of diets containing dried plums on the number of colonic precancerous lesions (aberrant crypts, ACs), fecal bile acid concentration, and cecal bacterial enzyme activities related to colon cancer risk. Rats were fed one of four diets: a basal diet (a modified AIN-93G diet), a low-concentration dried plum diet (LCDP, 4.75% dried plum powder), a high-concentration dried plum diet (HCDP, 9.5% dried plum powder), or a diet matched to the carbohydrate content of the HCDP diet (CH-M) for 10 days. All animals were then administered azoxymethane (15 mg/kg, s.c., given two times, 1 wk apart) and fed their respective diets for 9 additional weeks. The number of AC foci (ACF), large ACF (>3 AC/ACF), or ACF multiplicity (AC/ACF) did not differ among the four groups. When compared with the basal diet, rats fed the LCDP diet had significantly lower concentrations of total fecal bile acids, deoxycholic acid, and hyodeoxycholic acid. Rats fed the HCDP diet had significantly lower fecal concentrations of lithocholic acid and hyodeoxycholic acid. The LCDP and HCDP diets significantly decreased the cecal activity of 7α-dehydroxylase, and the LCDP also had lower β-glucuronidase activity. The LCDP, HCDP, and CH-M groups had significantly greater cecal nitroreductase activities than the basal group. There was a significant correlation between 7α-dehydroxylase activity and fecal lithocholic acid concentration. Compared with the basal diet, both the LCDP and HCDP diets greatly increased cecal supernatant oxygen radical absorbance capacity (ORAC). These results suggest that, although dried plums did not reduce ACF number, they favorably altered other colon cancer risk factors.

Bile acid induces hydrophobicity-dependent membrane alterations

Elevated concentrations of fecal bile acids are a known risk factor for colon cancer, owing to alterations in cellular signaling. In colonic cells, where bile acid uptake is minimal, the hydrophobicity-induced membrane perturbation and alterations have been proposed, but these membrane alterations are largely uncharacterized. In this study, we examined the determinants and characteristics of bile acid-induced membrane alterations, utilizing PKCα activation and cholesterol up-regulation as model indicators. We found that bile acid-induced PKCα activation is a function of hydrophobicity and correlated with alteration in membrane lipid composition, as evident by the significant up-regulation in membrane cholesterol and phospholipid. We found that bile acid do not cause cell membrane disruption at a concentration sufficient to activate PKCα, but do induce drastic alterations in membrane composition. Bile acid also induced the modification and up-regulation of caveolin-1 in a hydrophobicity-dependent manner, implying widespread receptor dysregulation. Similarly, ERK1/2 activation was observed only in response to hydrophobic bile acids, suggesting hydrophobicity-induced caveolar or membrane stress. Experiments with sodium lauryl sarcosine and cholesteryl hemisuccinate showed that bile acid-induced membrane alterations can be mimicked by hydrophobic molecules unrelated to bile acids, strongly implicating hydrophobicity as an important determinant of bile acid signaling.

Possible Mechanisms Behind the Differential Effects of Soy Protein and Casein Feedings on Colon Cancer Biomarkers in the Rat

: In the present studies, several hypotheses were tested to explain previously reported differential effects of soy and casein on colon cancer biomarkers like cell proliferation, fecal fat, fecal bile acid, alkaline phosphatase, and magnesium excretion in rats. In Study 1, the effect of methionine, a limiting amino acid in soy protein and an amino acid that is thought to have a marked effect on colonic cell proliferation, was tested. It was concluded that methionine up to 1% in the diet had no effect on cell proliferation, using the 3H-thymidine assay. The same study revealed that fecal alkaline phosphatase excretion is a good marker for colonic epithelial damage and fecal magnesium excretion is not. In Study 2, the hypothesis was tested that soy fractions enriched with isoflavones and saponins may increase fat excretion and so influence colonic cell proliferation in rats. It was indeed shown that soy protein isolate and an ethanolic extract from soy protein isolate slightly increased fecal fat excretion (up to 1.7-fold). However, fecal water bile acid and free fatty acid concentrations were decreased after feeding soy protein-based diets compared with casein, and no difference in fecal alkaline phosphatase excretion was observed. In Study 3, the lytic potential of soy saponins and the interaction between saponins and some lytic bile acids were tested in vitro. Data suggest a protective effect from soy saponins by reducing lytic activity of cholic acid. The overall conclusion is that soy protein compared with casein influences several colon cancer risk parameters, indicating a more protective rather than a stimulating effect on colon cancer risk.

Beef Tallow Increases Apoptosis and Decreases Aberrant Crypt Foci Formation Relative to Soybean Oil in Rat Colon

: Although epidemiological studies have implicated red meat as increasing colon cancer risk, animal studies have generally not been supportive of such an effect. This study examined red meat components, such as beef protein and tallow, on markers of colon cancer risk. Rats administered dimethylhydrazine were fed either casein or beef protein as the protein source and soybean oil or tallow as the fat source in a 2 × 2 factorial design for 9 wk. There were fewer preneoplastic lesions [aberrant crypt foci (ACF)] and a greater apoptotic labeling index (P < 0.05) in the distal colonic mucosa of rats fed tallow compared with soybean oil. Fecal bile acid concentrations were significantly lower in rats fed tallow compared with soybean oil. There were no significant differences in mucosal cell proliferation. No significant effects were found due to protein source or to interactions between fat and protein sources for ACF, cell proliferation labeling indexes, or bile acid concentrations. However, there was a significant protein by fat source interaction for the apoptotic labeling index. The decreased number of ACF, decreased fecal bile acid concentration, and increased mucosal apoptosis with tallow consumption are not consistent with a role for this fat in increasing risk of colon cancer.

Effects of a novel pomace fiber on lipid and cholesterol metabolism in the hamster

Water-insoluble fiber-rich fraction (WIFF) was isolated from the pomace of Averrhoa carambola, which is popular in Asia. The effects of WIFF-added diet on the lipid and cholesterol metabolism in hamsters were investigated and compared with those of cellulose-added and fiber-free diet as controls. Experimental results showed that the consumption of carambola WIFF decreased ( P < 0.05) the concentrations of serum triacylglycerol, serum total cholesterol, and liver cholesterol, and increased ( P < 0.05) the concentrations of fecal total lipids, fecal cholesterol, and fecal bile acids. The intake of WIFF also increased the fecal bulk and moisture. These pronounced cholesterol- and lipid-lowering effects of WIFF might be attributed to its ability to enhance the excretion of cholesterol and bile acids via feces. Our results suggested that carambola WIFF is used as a promising cholesterol-lowering ingredient in human diets or new formulations of fiber-rich functional foods.