Faecal bile acids

It is well recognised that the faecal bile acid content of random stool samples is highly variable with marked daily variation.Therefore, studies testing the association between luminal bile acid exposure and the presence of colorectal neoplasia have usually measured serum bile acid levels, which demonstrate less variability and are believed to reflect the total bile acid pool more accurately. Serum DCA levels have been shown to be higher in individuals with a colorectal adenoma compared with individuals without a neoplasm. Only one study has assessed future risk of CRC in a prospective study of serum bile-acid levels. The study was hampered by the small sample size (46 CRC cases). There were no significant differences in the absolute concentrations of primary and secondary bile acids or DCA/CA ratio between cases and controls although there was a trend towards increased CRC risk for those with a DCA/ CA ratio in the top third of values (relative risk 3.9 [95% confidence interval 0.9-17.0 = 0.1]). It will be important to test the possible utility of the DCA/ CA ratio as a CRC risk biomarker in larger, adequately powered studies. A recent study has demonstrated increased levels of allo-DCA and allo-LCA metabolites in the stool of CRC patients compared with healthy controls. ... 

Faecal bile-acid content was increased in colestimide-supplemented mice consistent with the mode of action of the BAS. In addition, faecal lipid content was raised in treated animals, suggesting reduced lipid absorption, presumably via the lowering of duodenal bile-acid concentration. 

Table 5.4.1 Calibration statistics of faecal bile acids (Bas reprinted from [16]). CA Cholic acid, CDCA chenodeoxycholic acid, DCA deoxycholic acid, LCA lithocholic acid ... 

Slightly hindered hydroxyl groups of bile acids can be silylated according to the procedure of Makita and Wells [319] methyl esters of bile acids, prepared by treatment with diazomethane, are dissolved in anhydrous pyridine (ca. 1 ml per 10 mg) and 0.1 ml of HMDS and 0.03 ml of TMCS are added to this solution. After standing for 10 min at room temperature an aliquot of the reaction mixture is injected directly. The method was applied to the determination of faecal bile acids in the rat. Other workers [320] investigated the retention behaviour of 52 persilylated methyl esters of urine acids on QF-1, OV-1 and OV-17 stationary phases. They correlated the data expressed as relative retention times with the structures of the compounds. 

D6. Dewael, J., Raaymakers, C. E., and Endeman, H. J., SimpliRed quantitative determination of total faecal bile acids. Clin. Chim. Acta 79, 465-470 (1977). 

Some further examples of the application of TLC may be cited a procedure for two dimensional separation [179] analysis of bile from various species [76] fractionation of bile lipids into groups [128] metabolism [73] and analysis of human faecal bile acids [153 a] quantitative determination of free [203] and bile acid conjugates [202] in serum. 

M. Venturi, R. J. Hambly, B. Glinghammar, J. J. Rafter and I. R. Rowland, Genotoxic activity in human faecal water and the role of bile acids a study using the alkaline comet assay. Carcinogenesis, 1997,18(12), 2353. 

They are useful only in hyperlipoproteinemias involving elevated levels of LDL i.e. type Ila, lib and V. They are basic ion exchange resins. They are neither digested nor absorbed in the gut. They bind bile acids in intestine and interrupt their entero-hepatic circulation, leading to increased faecal excretion of bile salts and cholesterol. There is increased hepatic conversion of choles-terol to bile acids. More LDL receptors are expressed on liver cells leading to increased clearance of IDL, LDL and indirectly of VLDL. 

Steatorrhoea is the formation of non-solid faeces. Floating stools, due to excess fat, are oily in appearance and foul smelling. There is increased fat excretion, which can be measured by determining the faecal fat level. Possible biological causes can be lack of bile acids (due to liver damage or hypolipidaemic drugs), defects or a reduction in pancreatic enzymes (lipase), and defective mucosal cells. The absence of bile acids will cause the faeces to turn grey or pale. 

Weststrate, J.A. et al., Safety evaluation of phytosterol esters. Rart 4. Faecal concentrations of bile acids and neutral sterols in healthy normolipidaemic volunteers consuming a controlled diet either with or without a phytosterol ester-enriched margarine. Food Chem. Toxicol, 37, 1063, 1999. 

In the 1950s and 1960s anion-exchange resins, such as colestyramine, were developed with the aim of binding bUe acids in the intestine, which originate from cholesterol elimination in the liver, and thus disrupt their enterohepatic circulation. The sequestered bile acids are then excreted with the faecal stools. Since the transport of the bile acids back to the liver can no longer occur, the serum cholesterol level drops. 

Dietary fat and cholesterol metabolism. Faecal elimination of bile acids and... 

C. D. Moutafis, L. A. Simons, N.B. Myant, P. W. Adams and V. Wynn, The effect of cholesteryramine on the faecal excretion of bile acids and neutral steroids in familial hypercholesterolaemia. Atherosclerosis 26 329 (1977). 

T.A. Miettinen and A. Aro, Faecal fat, bile acid excretion, and body height in familial hypercholesterolaemia and hyper-glyceridaemia, Scand. J. Clin. Lab. Invest. 30 85 (1972). 

S. Tarpila, T.A. Miettinen, and L. Metsaranta, Effects of bran on serum cholesterol, faecal mass, fat, bile acid and neutral sterols, and biliary lipids in patients with diverticular disease of the colon. Gut 19 137 (1978). 

In this model the secondary bile acid sodium deoxycholate appears to be neither tropic nor co-carcinogenic to hypoplastic defunc-tioned colon. The previously cited experiment showing that bile and pancreatic juice could stimulate adaptive mucosal hyperplasia and carcinogenesis after surgical diversion involved distal gut remaining in continuity with the faecal stream[29]. Thus any effect of bile acids in promoting colorectal neoplasia or in maintaining mucosal cell turnover is likely to depend in part on other luminal factors. 

Neomycin precipitates bile acids and fatty acids from micellar solutions in vitro [279] and promotes faecal excretion of bile acids in man [280], facts supporting the hypothesis that this is due to the ability of the drug to interact with bile and fatty acids during the micellar phase of lipid absorption [281]. Precipitation is more complete with taurochenodeoxycholate micelles than with taurocholate micelles and of the derivatives of neomycin studied dimethylamino-propyl neomycin was the most active, followed in order by neomycin, dodeca-iV-methyl neomycin hexamethochloride and N-methylated neomycin [281]. Hexa-N-acetyl neomycin failed to precipitate any of the micellar components. The same order of activity was found when the compounds were tested for their hypocholesterolaemic effect in newborn chicks [281]. 

The characteristic features of the coliforms are non-sporing, Gram-negative rods, which are bile tolerant and able to ferment lactose at 37 °C producing acid and gas within 48 hours. The term faecal coliform was used to describe coliforms capable of fermenting lactose to acid and gas within 24 hours at 44 °C. The term thermotolerant coliforms is now used more commonly in the UK, although the term faecal coliform is still widely used elsewhere. It should be pointed out that not all thermotolerant coliforms are faecal in origin. 

Chitosan also has hypocholesterolemic effects and acts as an adjuvant to weight loss in rat studies [31,32]. Studies have reported that chitosan reduced the concentration of plasma cholesterol in animals [33,34] and type If diabetes patients in combination with hypercholesterolemia [33]. This property is being attributed to the positive charge of the molecule that binds to fatty acids (released from consumed fat) and bile salt components, which results in disrupted lipid absorption in the gut [5]. Also, chitosan is dissolved in the stomach, emulsifying the fat and forming a gel in the intestine which entraps fat and prevents intestinal absorption [35,36]. Chitosan forms a floccule in the duodenum which entraps dietary oil [37]. However, these effects are still controversial [31,38,39]. Actually, van Bennekum et al. [32] suggested that the incorporation of chitosan in the diet of rats reduces cholesterol (food) intake, but did not affect either intestinal cholesterol absorption or faecal sterol output. 

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