Total Fecal Bile Acid Excretion Research Articles

Sexual dimorphism: increased sterol excretion leads to hypocholesterolaemia in female hyperbilirubinaemic Gunn rats.

Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to hypocholesterolaemia remain unknown. Therefore, this study aimed to investigate cholesterol synthesis, transport and excretion in mutant Gunn rats. Adult Gunn and control rats were assessed for daily faecal sterol excretion using metabolic cages, and water was supplemented with [1‐13C]‐acetate to determine cholesterol synthesis. Bile was collected to measure biliary lipid secretion. Serum and liver were collected for biochemical analysis and for gene/protein expression using RT‐qPCR and western blot, respectively. Additionally, serum was collected and analysed from juvenile rats. A significant interaction of sex, age and phenotype on circulating lipids was found with adult female Gunn rats reporting significantly lower cholesterol and phospholipids. Female Gunn rats also demonstrated elevated cholesterol synthesis, greater biliary lipid secretion and increased total faecal cholesterol and bile acid excretion. Furthermore, they possessed increased hepatic low‐density lipoprotein (LDL) receptor and SREBP2 expression. In contrast, there were no changes to sterol metabolism in adult male Gunn rats. This is the first study to demonstrate elevated faecal sterol excretion in female hyperbilirubinaemic Gunn rats. Increased sterol excretion creates a negative intestinal sterol balance that is compensated for by increased cholesterol synthesis and LDL receptor expression. Therefore, reduced circulating cholesterol is potentially caused by increased hepatic uptake via the LDL receptor. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).Key points Female adult hyperbilirubinaemic (Gunn) rats demonstrated lower circulating cholesterol, corroborating human studies that report a negative association between bilirubin and cholesterol concentrations.Furthermore, female Gunn rats had elevated sterol excretion creating a negative intestinal sterol balance that was compensated for by elevated cholesterol synthesis and increased hepatic low‐density lipoprotein (LDL) receptor expression.Therefore, elevated LDL receptor expression potentially leads to reduced circulating cholesterol levels in female Gunn rats providing an explanation for the hypocholesterolaemia observed in humans with elevated bilirubin levels.This study also reports a novel interaction of sex with the hyperbilirubinaemic phenotype on sterol metabolism because changes were only reported in females and not in male Gunn rats.Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).

Longitudinal assessment of taurine and amino acid concentrations in dogs fed a green lentil diet.

A recent association between the inclusion of pulses in canine diets and taurine deficiency has become a prevalent issue in the pet food industry. Although dogs do not currently have a nutritional requirement for taurine, taurine deficiencies that do occur can result in serious health issues, such as dilated cardiomyopathy. The objective of this study was to determine the circulating concentrations of plasma and whole blood taurine, indispensable and dispensable amino acid concentrations in the plasma, and taurine and creatinine concentrations in the urine of adult dogs fed a green lentil diet. Twelve adult, intact, female beagles were randomly assigned to a diet containing 45% green lentils (GLD) or a poultry byproduct meal diet (CON) for 90 d. Fresh urine samples were collected every 30 d and analyzed for taurine and creatinine concentrations. A blood sample was also collected every 30 d and analyzed for amino acids including taurine. Animal procedures were approved by the University of Illinois Institutional Animal Care and Use Committee. All diets were formulated to meet or exceed the nutrient requirements for adult dogs at maintenance. The concentrations of taurine in the plasma and whole blood showed no differences (P > 0.05) between dietary treatments or across time points. Similarly, no differences (P > 0.05) in plasma methionine concentrations were observed between treatments or across time points. A treatment effect (P < 0.05) showed dogs fed GLD had higher total primary fecal bile acid excretion compared with dogs fed CON. The differential abundance of fecal microbial communities showed Firmicutes as the predominant phyla in dogs fed both GLD and CON, with Bacteroidaceae, Erysipelotrichaceae, and Lactobacillaceae as predominant families in dogs fed GLD. The α-diversity of dogs fed GLD (P < 0.05) was lower than in dogs fed CON. These data suggest that the inclusion of 45% green lentil in extruded diets does not lower whole blood and plasma taurine concentrations during a 90-d period and is appropriate for use in a complete and balanced formulation for dogs.

242 Effects of different carbohydrate sources on taurine status in healthy Beagle dogs

Abstract Consumption of grain-free (GF) diets has recently been linked to canine dilated cardiomyopathy in selected dog breeds. Soluble fiber present in GF carbohydrate sources may be contributing to taurine depletion, thus affecting heart health. The objective of this study was to evaluate the effects of different carbohydrate sources on taurine status in healthy Beagle dogs. Two practical diets sufficient in sulfur-amino acids and taurine were formulated with the same proportion of carbohydrate sources: a grain-based (GB) containing sorghum, millet, and spelt, and a GF containing peas, potatoes and tapioca starch. Twelve Beagle dogs were fed experimental diets for 4-wk in a randomized complete block design. The morning prior to feeding experimental diets (baseline) and two and four weeks after, markers of taurine metabolism were analyzed in blood, urine, and fresh fecal samples. Data were analyzed as a change from baseline in a repeated measures model by GLIMMIX (SAS, version 9.4) in which the main effects of time, diet, and their interaction were evaluated. Greater concentrations of taurine in plasma (158 vs. 117 nmol/mL) and whole blood (254 vs. 234 nmol/mL) were observed during experimental period compared to baseline. An increase in plasma methionine was also observed during experimental period compared to baseline (64 vs. 57nmol/mL). Dogs fed GF exhibited higher plasma taurine concentration compared to those fed GB (181 vs. 138 nmol/mL). There were no significant effects of diet, time, or their interaction on plasma cystine concentration, urinary taurine:creatinine ratio, or total fecal bile acid (BA) excretion (P &amp;gt; 0.05). However, dogs fed GF had greater fecal primary BA (26 vs 14%) as a proportion of total BA compared to those fed GB. This study suggests that GF diets do not impair taurine blood concentration, but the increased proportion of fecal primary BA may decrease recycling of taurine through enterohepatic circulation.

Methods for diagnosing bile acid malabsorption: a systematic review

BackgroundBile acid malabsorption (BAM) and bile acid-related diarrhea represent an under-recognized cause of chronic diarrhea mainly because of limited guidance on appropriate diagnostic and laboratory tests. We aimed to perform a systematic review of the literature in order to identify and compare the diagnostic accuracy of different diagnostic methods for patients with BAM, despite a proven gold standard test is still lacking.MethodsA PubMed literature review and a manual search were carried out. Relevant full papers, evaluating the diagnostic accuracy of different methods for BAM, were assessed. Available data were analyzed to estimate the sensitivity and specificity of each published test.ResultsOverall, more than one test was considered in published papers on BAM. The search strategy retrieved 574 articles; of these, only 16 were full papers (with a total of 2.332 patients) included in the final review. Specifically, n = 8 studies used 75Selenium-homotaurocholic-acid-test (75SeHCAT) with a < 10% retention threshold; n = 8 studies evaluated fasting serum 7-α-hydroxy-4-cholesten-3-one (C4); n = 3 studies involved total fecal bile acid (BA) excretion over 48 h; n = 4 studies assessed fibroblast growth factor 19 (FGF19). 75SeHCAT showed an average sensitivity and specificity of 87.32 and 93.2%, respectively, followed by serum C4 (85.2 and 71.1%) and total fecal BA (66.6 and 79.3%). Fasting serum FGF19 had the lowest sensitivity and specificity (63.8 and 72.3%). All the extracted data were associated with substantial heterogeneity.ConclusionsOur systematic review indicates that 75SeHCAT has the highest diagnostic accuracy for BAM, followed by serum C4 assay. The diagnostic yield of fecal BA and FGF19 assays is still under investigation. Our review reinforces the need for novel biomarkers aimed to an objective detection of BAM and therefore improving the management of this condition.

Biomarkers for bile acid diarrhoea in functional bowel disorder with diarrhoea: a systematic review and meta-analysis

There is no universally available laboratory test to diagnose bile acid diarrhoea (BAD).ObjectiveTo conduct a systematic review and meta-analysis to identify a biomarker for idiopathic BAD in patients with functional...

Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome.

About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion. To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam. A single-centre, unblinded, single-dose trial of effects of colesevelam, 1875mg [3 tablets (625mg tablets)] orally, twice daily, for 10days on total 48-h faecal bile acid excretion and fasting serum C4 (7α-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8days prior and 8days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4. Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat. Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.

Genetic variation in GPBAR1 predisposes to quantitative changes in colonic transit and bile acid excretion.

The pathobiology of irritable bowel syndrome (IBS) is multifaceted. We aimed to identify candidate genes predisposing to quantitative traits in IBS. In 30 healthy volunteers, 30 IBS-constipation, and 64 IBS-diarrhea patients, we measured bowel symptoms, bile acid (BA) synthesis (serum 7α-hydroxy-4-cholesten-3-one and FGF19), fecal BA and fat, colonic transit (CT by scintigraphy), and intestinal permeability (IP by 2-sugar excretion). We assessed associations of candidate genes controlling BA metabolism (KLB rs17618244 and FGFR4 rs351855), BA receptor (GPBAR1 rs11554825), serotonin (5-HT) reuptake (SLC6A4 through rs4795541 which encodes for the 44-bp insert in 5HTTLPR), or immune activation (TNFSF15 rs4263839) with three primary quantitative traits of interest: colonic transit, BA synthesis, and fecal BA excretion. There were significant associations between fecal BA and CT at 48 h (r = 0.43; P < 0.001) and IP (r = 0.23; P = 0.015). GPBAR1 genotype was associated with CT48 (P = 0.003) and total fecal BA [P = 0.030, false detection rate (FDR) P = 0.033]. Faster CT48 observed with both CC and TT GPBAR1 genotypes was due to significant interaction with G allele of KLB, which increases BA synthesis and excretion. Other univariate associations (P < 0.05, without FDR correction) observed between GPBAR1 and symptom phenotype and gas sensation ratings support the role of GPBAR1 receptor. Associations between SLC6A4 and stool consistency, ease of passage, postprandial colonic tone, and total fecal BA excretion provide data in support of future hypothesis-testing studies. Genetic control of GPBAR1 receptor predisposing to pathobiological mechanisms in IBS provides evidence from humans in support of the importance of GPBAR1 to colonic motor and secretory functions demonstrated in animal studies.

583 GpBAR1 Genotype Predicts Bowel Function and Pathophysiology in Diarrhea-Predominant Irritable Bowel Syndrome

Background: Genetic predisposition in irritable bowel syndrome (IBS) is supported by prior association studies (Camilleri et al AJP 302:G1075-G1084, 2012). To date, no single genetic predisposition has been convincingly associated with symptoms and relevant quantitative traits in IBS. Aim: To identify candidate genes predisposing to symptoms, colonic transit, bile acid disturbances, and epithelial permeability in IBS.Methods:We assessed associations of variations in candidate genes controlling bile acid (BA) metabolism (KLB and FGFR4), BA receptor GPBAR1 (or TGR5), serotonin reuptake (5HTTLPR) or immune activation (TNFSF15) with bowel function, BA synthesis and total fecal BA, colonic transit (CT) and intestinal permeability (IP) in 30 healthy volunteers (HV), 30 patients with IBS-C (constipation) and 64 with IBS-D (diarrhea) (by Rome III criteria). Colonic tone and sensation were also measured by barostat in 48 IBS-D patients. Primary endpoints assessed in all participants were: fasting serum C4 (screen for hepatic BA synthesis rate), total fecal BA and fat excretion (per 48h on 100g fat diet), overall CT by scintigraphy (geometric center, GC) at 24h and 48h, intestinal and colonic permeability by urine mannitol excretion at 0-2h and 8-24h following 2-sugar ingestion test. Candidate genotype analysis of blood DNA was conducted using PCR-based methods: rs4795541 (5HTTLPR); rs351855 (FGFR4); rs17618244 (KLB); rs11554825 (GPBAR1); rs4263839 (TNFSF15). Bowel functions, C4, total and individual fecal BA, CT, colonic sensation, and IP were compared in IBS-C, IBS-D and HV. We used Spearman correlation to explore relationships of total fecal BA with CT and IP. The univariate associations of each genotype were assessed in the total set of participants by the KruskalWallis test (2 degrees of freedom general genetic model). Results: There were expected differences in IBS-C, IBS-D and HV groups in number of BMs, stool consistency and ease of passage, CT (GC48h), IP, fecal fat, serum FGF19 and C4, and total fecal BA (table). There were significant associations between total fecal BA and CT GC48 (r=0.43; p<0.001) and IP (r=0.23; p=0.015). There were significant (p<0.05) univariate associations between: a) GPBAR1 and symptom phenotype, gas sensation ratings, total fecal BA excretion, and CT GC48h. There were weaker associations of GPBAR1 variation with BM frequency and gas sensation threshold (both p<0.1); b) 5HTTLPR and stool consistency and ease of passage, postprandial colonic tone, and total fecal BA excretion; c) FGFR4 and IBS symptom phenotype, postprandial colonic tone, pain sensation threshold and serum FGF19 (p=0.06). Variations in TNFSF15 and KLB were not associated with any traits. Conclusion: Genetic control of 5HT reuptake and GPBAR1 receptor predisposes to symptoms and key pathophysiological mechanisms in IBS. Support: NIH DK92179

Soy protein isoflavones differentially regulate liver X receptor isoforms to modulate lipid metabolism and cholesterol transport in the liver and intestine in mice

Liver X receptor (LXR)α regulates the genes involved in cholesterol, fatty acid and glucose metabolism. Soy protein (SP) consumption reduces the hepatic accumulation of cholesterol and triacylglycerol, and improves insulin sensitivity. However, it is not known whether these effects are mediated via LXRα. We therefore investigated whether the consumption of SP regulates metabolic changes in cholesterol metabolism and insulin sensitivity via LXRα. Wild-type (WT) and Lxrα(-/-) (Lxrα, also known as Nr1h3) mice were fed an SP diet with or without cholesterol for 28 days. The expression of LXRα target genes was measured in liver and intestine, as were hepatic lipid content and faecal bile acid concentration. Oral glucose and insulin tolerance tests were also performed. Hepatocytes were used to study the effect of isoflavones on LXR activity. The livers of WT and Lxrα(-/-) mice fed an SP high-cholesterol diet showed less steatosis than those fed casein. The SP diet increased the expression of the ATP-binding cassette (ABC) sub-family genes Abca1, Abcg5 and Abcg8 in the liver and intestine, as well as increasing total faecal bile acid excretion and insulin sensitivity in WT mice compared with mice fed a casein diet. However, these effects of SP were not observed in Lxrα(-/-) mice. The SP isoflavone, genistein, repressed the activation of LXRα target genes by T0901317, whereas it stimulated the activation of LXRβ target genes. The AMP-activated protein kinase inhibitor, compound C, had the opposite effects to those of genistein. Our results suggest that SP isoflavones stimulate the phosphorylation of LXRα or LXRβ, resulting in different biological effects for each LXR isoform.

Effects of Colesevelam HCl on Sterol and Bile Acid Excretion in Patients with Type IIa Hypercholesterolemia

Colesevelam HC1 is a potent bile acid-binding polymer. This study's aim was to determine effects of colesevelam HCl on sterol and bile acid excretion in patients with type IIa hypercholesterolemia. Twenty-four patients (low-density lipoprotein cholesterol, 130 to 220 mg/dL) enrolled in an open-label, parallel-design study, entered an American Heart Association/National Cholesterol Education Program diet for 6 weeks and were randomized to colesevelam HCl, 2.3 or 3.8 g/day for 4 weeks. In an apparent dose-related manner, respective mean serum concentrations HCl of low-density lipoprotein cholesterol decreased by 10% (P < 0.01) and 13% (P = 0.05), mean total cholesterol levels decreased by 4.9% (P = 0.05) and 6.1% (P = 0.09), and total fecal bile acid excretion showed median changes of +324% (P < 0.05) and +316% (P < 0.05). Colesevelam HCl did not affect fecal neutral sterol or fecal fatty acid excretion; however, 24-hr urinary mevalonic acid levels significantly increased in both treatment groups (P < 0.05). The cholesterol-lowering action of colesevelam HCl appears to be mediated through increased bile acid excretion.

Effects of Brewer's Yeast Cell Wall on Fecal Steroid Excretion in Rats.

To reveal the mechanism(s) of the cholesterol-lowering effect of brewer’s yeast cell wall (BYC), we examined the effect of BYC on fecal steroid excretion in rats fed a high-cholesterol and -fat (HCF) diet or a cholesterol-free standard (STD) diet. Male Sprague-Dawley rats were fed an HCF diet or an HCF diet supplemented with 5% or 10% BYC for 14 days. The addition of BYC to the HCF diet dose-dependently reduced the increment of serum total cholesterol concentration and increased the fecal bile acid and neutral steroid(cholesterol and coprostanol) excretion levels. In this experiment, a negative correlation between serum total cholesterol concentration and fecal bile acid excretion level was observed; however, a correlation between serum total cholesterol concentration and fecal neutral steroid excretion level was not observed. Next, male Sprague-Dawley rats were fed an STD diet or an STD diet supplemented with 5% or 10% BYC for 14 days, to investigate whether BYC could lower serum total cholesterol concentration in the rats with normal serum cholesterol concentrations. The addition of BYC to the STD diet also slightly increased the fecal bile acid excretion level; however, it did not affect the serum cholesterol concentration. Furthermore, we examined whether BYC can reduce the serum total cholesterol concentration in Sprague-Dawley rats fed an HCF diet prior to the administration of BYC, to increase the serum total cholesterol concentration. In this experimental model, BYC reduced serum total cholesterol concentration and increased fecal total steroid excretion level, and a negative correlation between serum total cholesterol concentration and fecal bile acid excretion level was observed. These results suggest that BYC reduces serum total cholesterol concentration by increasing fecal bile acid excretion level.

Wheat bran fiber and development of adenomatous polyps: evidence from randomized, controlled clinical trials

Mutations in oncogenes and tumor suppressor genes are thought to initiate and promote the pathway to colorectal cancer, leading to hyperproliferation, the development of adenomas, and progression to gross malignancy. Intervention at any of these steps can potentially prevent the development of cancer. Several randomized, controlled trials have investigated the effect of dietary interventions, including the addition of wheat bran fiber, on the development of adenomatous polyps. In a familial adenomatous polyposis trial, patients were treated with 4 g of ascorbic acid plus 400 mg of α-tocopherol per day alone or with a grain fiber supplement (22.5 g/day) over a 4-year period. On an actual-intake basis, the combined intervention inhibited the development of rectal polyps. However, the Toronto Polyp Prevention Trial found no significant differences in polyp recurrence rates between patients who were counseled to follow a low-fat, high-fiber diet and patients consuming a typical Western diet with placebo fiber. A 9-month study of patients with resected colon adenomas found that dietary wheat bran fiber significantly reduced total, primary, and secondary fecal bile acid concentrations and excretion rates. Such bile acid levels are thought to be related to the risk of developing cancer. The Australian Polyp Prevention Project reported that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large colorectal adenomas. These latter results suggest that intervention with a low-fat wheat bran supplemented diet inhibits the transition from smaller to larger adenomas, which may be a critical step in determining which adenomas progress to malignancy.

Consumption of enzyme resistant starch and cholesterol metabolism in normo- and hypercholesterolemic rats

The influence of raw and retrograded high amylose corn starch on cholesterol metabolism in normo- as well as hypercholesterolemic rats was studied. No effect on cholesterol metabolism was observed in normocholesterolemic rats. On the contrary, in hypercholesterolemic animals plasma free and total cholesterol concentrations were significantly lower when enzyme resistant starch was fed. Liver cholesterol concentrations were significantly decreased in rats given the hypercholesterolemic diet supplemented with retrograded high amylose corn starch. Total fecal bile acid excretion and bile acid spectrum were not changed by enzyme resistant starch consumption. Plasma total cholesterol concentrations showed a significantly negative correlation with fecal coprostanol excretion in hypercholesterolemic rats. However, there is no evidence that coprostanol is the only factor responsible for the observed hypocholesterolemic effect of enzyme resistant starch in cholesterol fed rats.

Dietary Stearic Acid Reduces Plasma and Hepatic Cholesterol Concentrations without Increasing Bile Acid Excretion in Cholesterol-Fed Hamsters1–4

Although there is general agreement that saturated fatty acids elevate plasma cholesterol concentrations, the relative effects of individual fatty acids on cholesterol and bile acid metabolism are less clear. In this study, cholesterol and bile acid responses to diets enriched in different saturated fatty acids were investigated in hamsters. The six diets examined were as follows: 5% fat (g/100 g) enriched in palmitic acid (16:0) with no cholesterol, 5% fat 16:0-enriched, 0.05% cholesterol (wt/wt), and four diets containing 0.05% cholesterol and 15% fat with each diet enriched in lauric (12:0), myristic (14:0), palmitic (16:0), or stearic acid (18:0). Total plasma cholesterol concentration was significantly greater in hamsters fed the 14:0-enriched diet relative to those fed the 18:0-enriched diet (P < 0.05). Both plasma and liver cholesterol concentrations of hamsters fed 18:0 did not differ from those of the group fed no dietary cholesterol. In all instances, differences in total plasma cholesterol were accounted for within the HDL fraction; no significant treatment differences in VLDL or LDL cholesterol were found. Total daily fecal bile acid excretion was higher in hamsters fed the 15% fat 16:0 diet compared with those fed no dietary cholesterol (P < 0.05), but not significantly different from other treatment groups. There was greater deoxycholic acid excretion (P < 0.05) from hamsters fed the 14:0 and 16:0 diets compared with those fed the 18:0-enriched diet. Small intestinal + gallbladder bile acids, an index of pool size, did not differ significantly among the groups. The observed relative hypocholesterolemic effect of stearic acid was not mediated by increased bile acid excretion.

Randomized, Double-Blinded, Placebo-Controlled Study of Effect of Wheat Bran Fiber and Calcium on Fecal Bile Acids in Patients With Resected Adenomatous Colon Polyps

Ongoing epidemiologic and nutritional studies suggest that colorectal carcinogenesis is consistent with complex interactions between genetic susceptibility and environmental and dietary factors. Among the dietary components found to reduce colon cancer risk are high intakes of dietary fiber and calcium. We designed and conducted a randomized, double-blinded, placebo-controlled trial involving supplementation of the customary dietary intake with fiber and calcium and measurements of fecal bile acids to examine the potential mechanisms by which added dietary interventions might reduce colorectal cancer risk. In a randomized, double-blinded, phase II study, we used a factorial design to measure the effects of dietary wheat bran fiber (2.0 or 13.5 g/day) in the form of cereal and supplemental calcium carbonate (250 or 1500 mg/day elemental calcium) taken as a tablet on fecal bile acid concentrations and excretion rates. Measurements were made at base-line randomization (i.e., after a 3-month placebo run-in period using 2.0 g wheat bran fiber plus 250 mg calcium carbonate) and after 3 and 9 months on treatment in a randomly selected 52-patient subsample of the 95 fully assessable study participants who had a history of colon adenoma resection. Concentrations of fecal bile acids, total, primary (i.e., chenodeoxycholic and cholic), and secondary (i.e., deoxycholic, lithocholic, and ursodeoxycholic), were measured in 72-hour stool samples by gas-liquid chromatography. All P values resulted from two-sided tests. All geometric mean fecal bile acid concentrations and excretion rates were lower at 9 months than at 0 months or 3 months on treatment in the high-dose fiber, high-dose calcium, and high-dose fiber/high-dose calcium treatment groups. The high-dose fiber effect at 9 months of supplementation was statistically significant with respect to virtually all geometric mean fecal bile acid concentrations and excretion rates. For example at 9 months versus 0 months, high-dose fiber supplementation caused a reduction in fecal concentrations of total bile acids (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003). High-dose calcium supplementation also had a significant, but lower, effect at 9 months versus 0 months on the geometric mean total bile acid (35% reduction; P = .044) and deoxycholic fecal bile acid (36% reduction; P = .052) concentrations. High-dose wheat bran fiber and calcium carbonate supplements given for 9 months are associated with statistically significant reductions in both total and secondary fecal bile acid concentrations and excretion rates in patients with resected colon adenomas. This study supports the hypothesis that one of the important ways in which a high intake of wheat bran fiber and calcium may reduce the risk of colorectal neoplasia and cancer is by reduction of the concentrations of fecal bile acids. Phase III studies of these agents in the prevention of adenoma recurrence are necessary to confirm this hypothesis and have now been initiated at multiple institutions.

Bile acid malabsorption as a cause of hypocholesterolemia seen in patients with chronic pancreatitis.

A determination of caloric consumption based on a dietary survey table, fat and cholesterol intake, and analyses of fecal fatty acids and neutral sterols, and bile acid analysis (gas chromatographic method) were conducted on 33 subjects (including 17 patients with chronic pancreatitis and 16 normal controls). The factors related to hypocholesterolemia in chronic pancreatitis (CP) patients were investigated and the following conclusions were obtained: (1) The total caloric intake and fat consumption by the CP patients were significantly lower with the exception of cholesterol consumption. (2) Significant increases were noted in fecal fat, neutral sterols, and bile acid excretion by the CP patients. (3) A significant positive correlation was noted between the total cholesterol and body mass index (BMI), reaffirming that the cholesterol level can be used as an indicator of nutritional status. (4) A significant negative correlation was noted between the serum total cholesterol and fecal bile acid excretion. These findings indicate that CP patients suffer from neutral sterol malabsorption, in addition to dietary fat maldigestion and bile acid malabsorption. Furthermore, bile acid malabsorption is cited as a factor in the development of hypocholesterolemia in CP patients.

Effects of oral calcium supplementation on intestinal bile acids and cytolytic activity of fecal water in patients with adenomatous polyps of the colon

Calcium has been proposed to prevent colon cancer in subjects at risk for this tumour. This effect is supposed to be due at least in part to binding the bile acids to calcium, making them insoluble and harmless. To evaluate the effects of oral calcium supplementation on intestinal bile acids, 19 patients with adenomatous colonic polyps were supplemented with 35.5 mmol Ca2+ daily for 12 weeks. Duodenal bile, 24-h feces and 24-h urine were collected before and at the end of the 12-week period. In duodenal bile proportional concentration of cholic acid increased (38 +/- 4 vs. 51 +/- 3%, P < 0.001), whereas that of chenodeoxycholic acid decreased (35 +/- 3 vs. 25 +/- 2%, P < 0.01). Total fecal bile acid excretion increased (950 +/- 126 vs. 1218 +/- 137 mumol 24 h-1, P < 0.01), with proportional concentrations of the main primary and secondary bile acids remaining the same. Cytolytic activity of fecal water, measured by the degree of lysis of erythrocytes by the water, decreased (45 +/- 8 vs. 30 +/- 7%, P < 0.05). Total excretion of calcium increased as expected from the supplementary dose. It is concluded that calcium supplementation markedly affects intestinal bile acids and lytic activity of fecal water and that, in view of similar results during 1-week calcium supplementation in young healthy subjects, these effects remain constant over at least 3 months and occur both in healthy persons and in patients at increased risk for colon cancer.

Bile Acid Metabolism in Rats Fed Two Levels of Corn Oil and Brans of Oat, Rye and Barley and Sugar Beet Fiber , , ,

High concentrations of fecal bile acids are associated with a higher incidence of colon cancer. Dietary changes that alter bile acid metabolism are therefore of interest. Here, we report the effect of feeding diets containing four fiber sources and two fat levels for 7 wk on bile acid excretion and small intestinal bile acids (an index of pool size) in rats. The fiber sources were oat bran, rye bran, barley bran and sugar beet fiber. Fiber-containing diets were 8% dietary fiber and contained either 5 or 20% corn oil. All fiber sources caused significantly greater fecal output compared with the fiber-free basal diet. All fiber sources also resulted in significantly (P < 0.05) lower fecal bile acid concentration compared with the fiber-free basal diet. Only rye bran resulted in significantly (P < 0.05) higher total fecal bile acid excretion. Oat bran resulted in a slightly but significantly (P < 0.05) higher quantity of small intestine bile acids compared with the other diets. Dietary fat level had no significant effect on fecal bile acid concentration or excretion or quantity of small intestinal bile acids. We conclude that all four fiber sources tested resulted in lower fecal bile acid concentration, by effectively causing greater fecal mass. Changes in dietary fat level as corn oil had no effect on fecal bile acids.

Plantago ovataseeds as dietary fibre supplement: physiological and metabolic effects in rats

In rats, the effects of a 4-week supplementation of a fibre-free elemental diet with 100 or 200 g Plantago ovata seeds/kg was compared with that of the husks and wheat bran. The seeds increased faecal fresh weight up to 100%, faecal dry weight up to 50% and faecal water content up to 50%. The husks, at the high concentration only, were more effective and wheat bran less effective. Length and weight of the small intestine were not greatly affected by the seeds, but both variables increased significantly in the large intestine. The husks had more pronounced effects, especially in the small intestine, and wheat bran almost no effect. Faecal bacterial mass as estimated from the 2,6-diaminopimelic acid output was increased to the greatest extent by the seed-containing diet and by the high concentration of husks, but to a lesser extent by wheat bran. Faecal and caecal protein content was enhanced by the seeds and wheat bran, but to a lesser extent by the husks. Total acetate in caecal contents or faeces was highest on the seeds and husks diet and not elevated by wheat bran. Total faecal bile acid excretion was stimulated and beta-glucuronidase (EC 3.2.1.31) activity reduced by both Plantago ovata preparations, but not by wheat bran. Mucosal digestive enzyme activities were inhibited to different degrees by all dietary fibres in the jejunum, and sometimes activated in the ileum. These results suggest that Plantago ovata seeds are a partly-fermentable dietary fibre supplement which increases stool bulk; metabolic and mucosa-protective effects are also probable.

Enhanced fecal excretion of bile acids by a new anion-exchange resin possessing a spacer arm in rats.

The effect of a new polystyrene-based, strongly basic, anion-exchange resin possessing an omega-oxobutyl chain as a spacer arm on the fecal bile acid excretion was investigated in rats and compared with that of Dowex 1-X2, chemically equivalent to cholestyramine. The new resin did produce a significant rise in the total fecal bile acid excretion with its ingestion for a period of 4 weeks. Its promoting activity proved to be 2.0- and 1.8-fold more potent than that of Dowex 1-X2 at the 3rd and 4th week, respectively. These results suggest that the introduction of a spacer arm between the polymer backbone and a functional group would lead to an improvement in the in vivo adsorptive efficiency of the resin.