Total Fecal Bile Acid Excretion Research Articles

Effect of change of fecal bile acid excretion achieved by operative procedures on 1,2-dimethylhydrazine-induced colon cancer in rats.

The effect of bile on the development of 1,2-dimethylhydrazine (DMH)-induced colon cancer was studied in male Wistar rats. Experimental operative models were created, in which in Group 1, the half intestinal tract, the ileum, and the right side of colon were released from bile. In Group 2, both sides of the colon contained bile. The sham operated animals formed Group 3. These techniques changed the concentration of bile acid in different parts of the colon, and the daily total fecal bile acid excretion as well. After DMH treatment, the relationship between these changes of bile acid level and the development of colon cancer was studied. Significantly more tumors than in the control group were found if the daily total bile acid level and the bile acid concentration in the left side of the colon were increased. Our findings show an unambiguous connection between the fecal bile acid level and the incidence of DMH-induced colon cancer.

Experimental colonic carcinogenesis: changes in faecal bile acids after promotion of intestinal tumours by small bowel resection in the rat.

Small bowel resection promotes the development of colonic tumours in azoxymethane treated rats. As high faecal bile acid concentrations are associated with colonic cancer and may be altered by resection, we have studied changes in faecal bile acid concentrations during promotion of colonic carcinogenesis by increasing small bowel resection. Twenty rats in each group underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg by 12 weekly subcutaneous injections, and faecal bile acid concentrations were measured at six and 16 weeks. Colonic tumour number rose from 0.6 per rat in the transection group to 1.6 per rat in the 50% resection group (p less than 0.01) but were not significantly different to transection values at 0.8 per rat in the 80% resection group. Total daily faecal bile acid excretion and bile acid concentrations fell with increasing resection from 14.2 (1.6) mg/rat/day and 5.8 (0.7) mg/g dry faeces respectively in the transection group to 6.5 (0.5) mg/rat/day and 2.9 (0.2) mg/g respectively in the 80% resection group (p less than 0.001). The greatest reduction was seen in the concentration of deoxycholic acid which has been particularly associated with the aetiology of colonic cancer. The promotion of colonic tumours following small bowel resection in carcinogen treated rats is unlikely to be mediated by changes in faecal bile acid concentration or composition.

Effect of activated carbon beads on serum lipid levels and fecal bile acid excretion in rats.

The effects of oral activated carbon beads on the total serum cholesterol and triglyceride levels and on the fecal bile acid excretion in rats fed a basal or high cholesterol diet containing 5% activated carbon beads for 6 weeks were investigated. The beads appeared to exert little effect on the growth rate of rats and no tendency towards constipation was also observed. Although treatment with activated carbon beads gave little influence on the total serum cholesterol and serum triglyceride levels in rats fed either a basal or high cholesterol diet, the beads did produce a significant rise in the total fecal bile acid excretion. The extra fecal bile acids resulted chiefly from an increase in lithocholic acid. Furthermore, the beads showed a tendency to inhibit absorption of dietary cholesterol from the gastrointestinal tract in rats fed a high cholesterol diet. These results suggested the possibility of activated carbon beads as a hypocholesterolemic agent through binding with bile acids in the intestine.

FECAL BILE ACID PROFILES OF JAPANESE PATIENTS WITH ADENOMATOUS POLYPS OF THE LARGE BOWEL

Bile acids have been implicated in carcinogenesis of the large bowel, and since epidemiological, clinical and histopathological studies suggest a link between adenomatous polyps and cancer of the large bowel, fecal bile acid profiles were studied in 33 patients with adenomatous polyps of the large bowel and these data were analyzed with particular reference to the distribution, multiplicity, size and degree of dysplasia of the polyps. The more polyps and the greater the severity of dysplasia, the higher was the excretion of total bile acids (mean mumol/day: single vs multiple polyps, 344.8 vs 369.1; mild vs moderate vs severe dysplasia, 347.5 vs 370.0 vs 399.3). However, in patients with larger polyps, total fecal bile acid excretion tended to be lower (mean mumol/day: large vs small polyps, 267.7 vs 389.5). These differences were not statistically significant. When fecal bile acid profiles were analyzed with respect to the extent of bacterial metabolism determined from the degree of dehydroxylation and oxidoreduction, there was a large variation with no consistency in relation to the factors studied among the polyp patients. Deconjugation of bile acids in feces was almost complete without difference among the patients. These results seem to indicate that the significance of bile acid in the development of adenomatous polyps in Japanese subjects is likely to be small.

Faecal bile acid profiles in patients with large bowel cancer in Japan.

To study the possible role of bile acids in carcinogenesis of the large bowel faecal bile acid profiles were analysed in detail in 14 patients with large bowel cancer and compared with 14 matched healthy subjects. The total faecal bile acid excretion was lower in the patients (297.3 +/- 402.8 mumol/day) than in the healthy subjects (470.6 +/- 231.1 mumol/day) (p less than 0.01), although the difference became insignificant when these data were expressed as mumol per wet or dry faecal weight. The faecal profiles of individual bile acids and their conjugates were similar in both groups except that 5 beta-chol-3-en-24-oic acid, a bacterial metabolite of sulpholithocholic acid, was found in nine cancer patients (64%) compared with only two healthy subjects (14%) (p less than 0.01). The significance of 5 beta-chol-3-en-24-oic acid in carcinogenesis needs further prospective and experimental studies.

The effect of meat protein and dietary fiber on colonic function and metabolism I. Changes in bowel habit, bile acid excretion, and calcium absorption

No satisfactory hypothesis has been put forward to explain the association internationally of high meat protein intakes with the high incidence of large bowel cancer. Since current evidence suggests that the development of colonic cancer is related to high fecal bile acid levels, low fecal weight, and slow transit through the gut we have measured these in four healthy subjects taking metabolically controlled diets of different protein and fiber content through three successive 3-week periods. The diets were low protein (LP) (62.7 g protein per day), high protein (HP) (136 g protein per day) meat being the main source of the extra protein, and high protein with added wheat fiber (HP + F). The change in protein intake was without significant effect on bowel habit (fecal frequency LP: 3.5 ± 0.7 HP 4.3 ± 0.8 stools per week; fecal weight LP 79.7 ± 10, HP 80.5 ± 11 g/day), mean transit time (MTT: LP 75 ± 11 hr, HP 70 ± 6 hr); or fecal bile acid excretion (LP 196 ± 13, HP 221 ± 19 mg/day). By contrast, adding 31 g dietary fiber from wheat to the HP diet significantly increased fecal weight to 210 ± 9 g/day, diluted 3-fold an inert marker in the stool, shortened MTT (50 ± 3 hr) and increased fecal bile acid excretion to 444 ± 27 mg/day. The change from LP to HP diet altered the route of calcium excretion, more appearing in the urine, while overall balance was maintained. When fiber was added to the HP diet all the subjects went into negative calcium balance although the period of observation was only 3 weeks. Meat protein cannot be related to the etiology of bowel cancer through an effect on stool weight, transit time, or total fecal bile acid excretion. The epidemiological associations either need reexamining or alternatively current theories of the cause of large bowel cancer should be revised.

Influence of diets high and low in animal fat on bowel habit, gastrointestinal transit time, fecal microflora, bile acid, and fat excretion.

Epidemiological observations and animal experiments suggest that large bowel cancer is related to serveral factors. Among them, high dietary intakes of animal fat, the presence in the colon of relatively high levels of bile acids, specific patterns of intestinal microflora, slow transit through the gut, and low stool weights. Under metabolic conditions we have observed the effect on these variables of dietes containing 62 or 152 g/day of fat mainly of animal origin in six healthy young men over 4-wk periods. No change attributable to the diet was observed in the subjects' bowel habit, fecal weight, mean transit time through the gut, or in the excretion of dry matter. Total fecal bile acid excretion was significantly higher on the high fat diet (320 +/- 120 mg/day) than on the low fat diet (139.7) +/- 63 mg/day) t test = 7.78 P less than 0.001 as also was the total fecal fatty acid excretion, 3.1+/-0.71 and 1.14+/-0.35 g/day, respectively t test = 11.4 P less than 0.001). The fecal microflora including the nuclear dehydrogenating clostridia were unaltered by the dietary changes as was fecal beta-glucuronidase activity. Dietary changes which increase animal fat intake clearly influence fecal bile acid excretion in a way that would favor the development of large bowel cancer if current theories prove to be true. Dietary fat however has no effect on overall colonic function so other components of the diet must be responsible for the observed associations of bowel cancer with slow transit and reduced fecal bulk.

Use of an elemental diet (Vivonex) in the management of bile acid-induced diarrhoea.

The effect of a low fat containing elemental diet (Vivonex) on faecal bile acid excretion was studied in six patients with cholerheic diarrhoea, two normal controls, and four patients with non-cholerheic diarrhoea. The total faecal bile acid excretion for the patients with bile acid-induced diarrhoea was significantly reduced fron 6-37+/- 1-64 mmol/24 h (mean +/- SEM) to 2-70 +/- 1-12 mmol/24 h during Vivonex treatment (p less than 0-05). A marked improvement in the diarrhoea of these patients occurred; the number of stools per day decreased and there was less urgency associated with the diarrhoea. No significant reduction in faecal bile acid excretion was observed for the control and non-cholerheic diarrhoea groups. An elemental diet of this type may be of value in the management of patients with bile acid-induced diarrhoea unresponsive to other forms of therapy, and may be of particular value in patients with Crohn's disease.

Effects of High Risk and Low Risk Diets for Colon Carcinogenesis on Fecal Microflora and Steroids in Man

We investigated the effects of a high meat mixed Western diet and a nonmeat diet, representing the dietary pattern of high and low risk areas for colon cancer, respectively, on fecal microflora dn on bile acid and neutral sterol patterns in man. The total anaerobic microflora as well as the count of Bacteroides, Bifidobacterium, Peptococcus, and anaerobic Lactobacillus were significantly higher during the period of consumption of a high meat mixed Western diet comparted with the nonmeat-diet consumption period. The difference in total fecal bile acid excretion was not significant between the two dietary periods. Fecal excretion of microbially modified bile acids and neutral sterols was decreased when subjects eating a high meat diet transferred to a nonmeat diet. These results support the fact that diet plays a modifying role on the composition of intestinal microflora, bile acids, and neutral sterols.

A modified assay of total faecal bile acid excretion for clinical studies

Faecal bile acid excretion was estimated in a clinical laboratory using gas liquid chromatography. The original method of Grundy et al was simplified so that quantitative thin layer chromatography was not required. Rigid dietary control or inpatient facilities were unnecessary for clinical studies. Control patients studied under these conditions had a daily faecal bile acid excretion of 0.37 +/- 0.13 g/day. Patients with ileal resections varied markedly with bile acid excretions ranging from 0.25--6.32 g/day (mean 2.36 +/- 1.11).

Steroid balance and tissue cholesterol accumulation in germfree and conventional rats fed diets containing saturated and polyunsaturated fats

Steroid balance studies were conducted on 24 conventional and 12 germfree male rats, 90-120 days old, fed diets containing either 20% safflower or 20% coconut oil. Both germfree and conventional rats fed the safflower oil diets had significantly lower serum cholesterol levels and significantly higher liver cholesterol levels than did the rats fed coconut oil. No significant differences in total fecal neutral sterols, coprostanol, Delta(7)-cholestenol, or total fecal bile acid excretion were seen between dietary groups of rats of either status. There was no evidence of qualitative differences in fecal bile acid excretion as a function of diet. The increased liver cholesterol was in the ester form, with cholesteryl linoleate the largest single component. There was no significant difference in the cholesterol content of the skin, muscle, adipose tissue, or gastrointestinal tract. The significance of a large increase in liver cholesteryl ester, lowered serum cholesterol, and no change in steroid excretion is discussed.

Total faecal bile acid excretion in children.

Total faecal bile acid excretion in children.