Rats fed high fat diets with increased calcium levels have fecal bile acid concentrations similar to those of rats fed a low fat diet (original) (raw)
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The relationship between faecal bile acids and the development of experimental colon cancer
British journal of experimental pathology, 1988
Human metabolic studies have suggested a positive association between dietary intake, faecal bile acid excretion and the development of colon cancer. Similar investigations in experimental models of this disease have also implicated faecal bile acids but in both animals and man the results remain equivocal. This study sequentially examines the outputs and concentrations of faecal bile acids in dimethylhydrazine (DMH) treated groups of rats (n = 10), killed at 5-weekly intervals from the 10th to 40th week following the first injection. The sequential results showed that both the output and concentration of faecal bile acids decreased with time and accompanied an increase in both the incidence and numbers of colonic neoplasms over the 40 weeks of the study. When the animals were grouped according to the histological classification of their tumours, the faecal bile acids did not differ between animals with and without tumours. Further, when the latter group were sub-divided into those ...
Ultrastructural Modifications of Intestinal and Colonic Mucosa Induced by Free or Bound Bile Acids
Cancer Research, 1981
There is substantial evidence that bile acids may enhance the colon tumorigenesis induced by chemical carcinogens and that agents stimulating increased bile acid excretion may show similar promoting or enhancing activity. To test the premise that these agents might modify topographical ultrastructure of the small intestine and colon in the absence of carcinogens, rats were fed for 6 weeks on chemically defined diets contain ing 2% levels of three commercial bile acid sequestrants or 15% levels of wheat bran, cellulose, pectin, or alfalfa. Major qualitative and quantitative deviations from normal morphology were observed with each of the three sequestrants. Similar but less dramatic modifications occurred with diets containing al falfa or pectin, both of which either â€b ind' â€b ile acids in vitro or result in increased bile acid excretion. Bran and cellulose, which neither â€ẫ€˜bind' â€b ile acids nor increase their fecal excre tion, were without significant effects on intestinal or colonic morphology. The morphological deviations observed with bile acid sequestrants were shown to be a direct response to free or bound bile acids by comparing the morphological modifica tions resulting from daily intracolonic infusions of free bile acids, sequestrant-bound bile acids, or the sequestrant alone.
European Journal of Clinical Investigation, 1993
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 f 4 vs. 51 k 3 % , P<O.OOI), whereas that ofchenodeoxycholic acid decreased (35 If: 3 vs. 25 5 2%, P < 0.01). Total fecal bile acid excretion increased (950 126 vs. 1218+ 137 pmol 24 h-', P<O*Ol), 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 f 8 vs. 30 f 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 by fresh human colonic contents: a comparison of caecal versus faecal samples
Gut, 2001
Background-Deoxycholic acid (DCA), implicated in the pathogenesis of gall stones and colorectal cancer, is mainly formed by bacterial deconjugation (cholylglycine hydrolase (CGH)) and 7dehydroxylation (7-dehydroxylase (7-DH)) of conjugated cholic acid (CA) in the caecum/proximal colon. Despite this, most previous studies of CGH and 7-DH have been in faeces rather than in caecal contents. In bacteria, CA increases 7-DH activity by substrate-enzyme induction but little is known about CA concentrations or CA/7-DH induction in the human colon. Aims and methods-Therefore, in fresh "faeces", and in caecal aspirates obtained during colonoscopy from 20 patients, we: (i) compared the activities of CGH and 7-DH, (ii) measured 7-DH in patients with "low" and "high" percentages of DCA in fasting serum (less than and greater than the median), (iii) studied CA concentrations in the right and left halves of the colon, and examined the relationships between (iv) 7-DH activity and CA concentration in caecal samples (evidence of substrate-enzyme induction), and (v) 7-DH and per cent DCA in serum. Results-Although mean CGH activity in the proximal colon (18.3 (SEM 4.40) ×10 −2 U/mg protein) was comparable with that in "faeces" (16.0 (4.10) ×10 − 2 U/mg protein) , mean 7-DH in the caecum (8.54 (1.08) ×10-4 U/mg protein) was higher (p<0.05) than that in the left colon (5.72 (0.85) ×10-4 U/mg protein). At both sites, 7-DH was significantly greater in the "high" than in the "low" serum DCA subgroups. CA concentrations in the right colon (0.94 (0.08) µmol/ml) were higher than those in the left (0.09 (0.03) µmol/ml; p<0.001) while in the caecum (but not in the faeces) there was a weak (r=0.58) but significant (p<0.005) linear relationship between 7-DH and CA concentration. At both sites, 7-DH was linearly related (p<0.005) to per cent DCA in serum. Interpretation/summary-These results: (i) confirm that there are marked regional diVerences in bile acid metabolism between the right and left halves of the colon, (ii) suggest that caecal and faecal 7-DH influence per cent DCA in serum (and, by inference, in bile), and (iii) show that the substrate CA induces the enzyme 7-DH in the caecum.
Gastroenterology, 1990
It has been suggested that supplemental dietary calcium decreases hyperproliferation of colonic epithelial cells because calcium precipitates and thus inactivates luminal bile acids. Therefore, 12 healthy men were studied before and after dietary calcium supplementation (35.5 mmol/day) to quantify intestinal associations of calcium, phosphate, and bile acids. The supplemental dietary calcium was almost completely (95%) recovered, mainly in feces. Calcium increased the fecal excretion of both phosphate (31%) and bile acids (53%) and decreased the ratio of dihydroxy to trihydroxy bile acids in duodenal bile almost twofold. In vitro studies showed that precipitation of glycodeoxycholic acid was caused by the formation of insoluble calcium phosphate. Watersoluble and calcium-associated amounts of phosphate and bile acids in feces were measured by resolubilization studies, using the calcium chelator ethylenediaminetetraacetate. In both the control and calcium periods, significant amounts of phosphate (80% and 90%) and bile acids (33% and 50%) were calcium-associated. Moreover, the calcium-induced increments in fecal phosphate and bile acids were completely calcium-associated. Calcium decreased the amount of water-soluble phosphate but not of bile acids. These results indicate that supplemental calcium stimulates formation of insoluble calcium phosphate in the intestinal lumen and thus increases binding of luminal bile acids.
Inhibition of human colonic epithelial cell proliferation in vivo and in vitro by calcium
Cancer research, 1986
Nine patients at high risk of developing colon cancer were placed on daily p.o. supplementation of 1500 mg of calcium for 4-8 weeks. The colonic epithelial cells in six of these patients showed a statistically significant decrease in their [3H]thymidine labeling indices in tissue culture so that they resembled those of patients at low risk of developing colon cancer. The three nonresponders had similar labeling indices before and after calcium supplementation. Biopsies from each of nine high-risk patients exhibited a decrease in proliferation when they were cultured in vitro with a high level of CaCl2 (2.2 mM compared with the 0.1 mM optimum value for proliferation). Two adenomas and two carcinomas showed a different pattern of response than normal cells, exhibiting no inhibition of growth at 2.2 mM CaCl2. These data indicate that the growth inhibition induced by high levels of extracellular calcium levels is lost at a stage in tumor development before cells become malignant.
Mechanisms of the intestinal effects of dietary fats and milk products on colon carcinogenesis
Cancer Letters, 1997
Dietary fat may promote colon cancer by increasing fatty acids (FA) and secondary bile acids (BA) in the colonic lumen. These cytotoxic surfactants can damage colonic epithelial cells and thus induce a compensatory hyperproliferation of crypt cells. Our studies show that the hyperproliferative effect of type and amount of dietary fat is not simply due to changes in colonic FA and BA. This indicates that an additional, at present unknown, cytotoxic factor is involved. The hyperproliferative effect of dietary fat is inversely related to the amount of calcium in the diet. In rat and man, dietary calcium precipitates colonic cytotoxic surfactants and thus inhibits luminal cytotoxicity. These inhibitory effects on metabolic risk factors suggest a preventive effect of dietary calcium on colon carcinogenesis.
Acta Medica Marisiensis, 2015
The aim of the study was to determine the level of secondary bile acids (SBA) in the diets and feces of mice and the variation of amount ingested/excreted if these SBA are administered as monotherapy or in 1:1 dose. Methods: The mice were divided into 4 groups and fed for 140 days with different diets. The control lot received a normal diet and the others received diets supplemented with 0.25% deoxycholic acid (DCA), 0.25% lithocholic acid (LCA) and 0.125% DCA+0.125% LCA. After 140 days, the mice feces were collected and homogenized to obtain a mixture for each lot from which the determinations of the studied SBA were performed. For the mice food evaluation, portions of 10 g from each of the 4 diets were subjected to the SBA determination. Results: The daily ingestion over more than 4 months of DCA or LCA added to the diet and administered as monotherapy determine a significantly increase of the SBA eliminated into the feces (the DCA level was 11x higher, and of the LCA 233x higher). If half of the LCA dose is replaced with DCA, the level of LCA in the feces gets comparable with that of the DCA (their combined amounts represents only 13x higher increase of these two bile acids in feces). Conclusions: The simultaneous ingestion and excretion of DCA and LCA can be considered as a particular situation ruled by endogenous mechanisms. This behavior represents an important observation, knowing that the bile acids effects in the colorectal cancer are dose dependent.