Fecal excretion of bile acids

There are several ways pectin could reduce serum cholesterol. In studies with human subjects, fecal excretion of bile acids, fatty acids, and total steroids increased when subjects were fed 15-40 g/day of pectin (58, 63, 64). Since pectin usually lowers serum cholesterol only when cholesterol is present in the diet, it seems that pectin might act by reducing cholesterol absorption. Several groups have found that in rats dietary... 

Cholestyramine resin also is helpful for the relief of pruritus associated with partial biliary obstruction and in conditions such as primary biliary cirrhosis. Cholestyramine increases fecal excretion of bile acids and reduces circulating and eventually systemic levels with relief of pruritus in -1-3 weeks. 

TABLE Vm. Daily Fecal Excretion of Bile Acids in Man... 

The major pathway of cholesterol elimination in the rat is via fecal excretion of bile acids. This pathway may be divided into two related events (a) the catabolism of cholesterol to bile acids and (b) the excretion of bile acids from the pool. Pituitary hormones may thus affect one or both of these processes. 

V. QUANTITATIVE FECAL EXCRETION OF BILE ACIDS BY GERMFREE AND CONVENTIONAL ANIMALS... 

Haust, H. L., and J. M. R. Beveridge Effect of varying t3rpe and quantity of dietary fat on the fecal excretion of bile acids in humans subsisting on formula diets. Arch. Biochem. 78, 367 (1958). 

Fecal steroid and lipid excretion. Fiber supplements from sugar cane residue (bagasse), administered to volunteers for 12 weeks, increased stool weights and stool fat excretion. Bagasse increased the daily loss of acid steroids and decreased transit time without alteration in fecal flora. The increased excretion of bile acids and fatty acids failed to lower the plasma cholesterol and TGs after 12 weeks ". 

Dietary fiber has a pronounced effect on the characteristics of the fecal mass and on the rate of passage of digest through the G1 trad, High fiber diets also play a role in the excretion of bile acids and cholesterol. 

Several other agents have beneficial effects on plasma lipid profiles occurring through various cellular mechanisms.89 Cholestyramine (Questran), for example, attaches to bile acids within the gastrointestinal lumen and increases the fecal excretion of these acids. This action leads to decreased plasma cholesterol concentrations because cholesterol breakdown is accelerated to replace the bile acids that are lost in the feces. 

Bile acid resins increase fecal excretion of bile salts f 15-20% f 10-25% t 3-5% Variable, depending on pretreatment level of triacylglycerols (may increase)... 

Most bile salts excreted in the feces are of the secondary type. Their formation is discussed in Section VII. The daily fecal excretion of bile salts in healthy subjects is highly variable and easily influenced by dietary alterations. Values from several studies are given in Table VIII. Bile salts virtually disappear from the stools during prolonged fasting, and turnover nearly ceases (19). Primary bile salts appear in the stools of patients with diarrhea (1). Patients taking cholestyramine excrete the usual pattern of secondary bile salts (57), so that apparently bacterial dehydroxylation of bile salts can occur in the presence of this resin. Patients with total external bile fistulas have no bile salts in the feces (2) this does not exclude transintestinal excretion of bile salts but makes it unlikely. As mentioned earlier, the predominance of chenodeoxycholic acid in blood and bile is often reflected in a predominance of lithocholate over deoxycholate in the feces (27). 

Neomycin is a polybasic, poorly absorbed antibiotic which forms insoluble precipitates with bile salts (99). It lowers serum cholesterol concentrations in man (100-102) and chickens (99) and increases fecal bile acid excretion. It inhibits the hepatotoxic effects of lithocholic acid ingestion in chickens (99) and prevents bacterial conversion of cholate to deoxycho-late (103). Neomycin, 6-12 g/day, induces a malabsorption syndrome, with mucosal changes similar to those of sprue (104). Bile salt metabolism is thus affected in at least three ways by neomycin (1) a binding effect similar to that of cholestyramine, (2) suppression of deconjugation and secondary bile formation caused by antimicrobial properties, and (3) possible impairment of absorption of bile salts by intestinal mucosa. The first probably accounts for most of the increased fecal excretion of bile salts. 

The methods available for the quantitation of bile acid metabolism in man have been reviewed recently by Hofmann et al. (53). The measurement can be performed by the following methods (a) fecal determination of bile acids, (b) fecal excretion of administered labeled bile acids, (c) isotope dilution, and (d) measurement of bile salt pool. 

Fecal bile acid elimination is markedly reduced in patients with liver cirrhosis (11,182,191), even if icterus and signs of biliary obstruction are absent (11,182). Since, in addition, the urinary excretion of bile acids is quantitatively, if not proportionally (81), negligible, it can be concluded that the overall bile acid synthesis is markedly depressed in liver cirrhosis (182). The administration of cholestyramine, which is associated with reduction of both serum bile acids (188,192,193) and urinary bile acids (88,182), augmented the fecal bile acid excretion to a very small extent only (182). This indicates that the ability of the parenchymal cells to increase their bile acid production is clearly decreased compared to that of normal subjects. Though the fecal neutral sterol excretion was also increased by cholestyramine, only a relatively small decrease in serum cholesterol was found, suggesting that the patients still were able to increase their cholesterol production (182). 

Of the hyperlipidemic drugs, clofibrate appears to decrease fecal elimination of bile acids (278-280). However, this decrease is less than the increase of the neutral steroid output, so the net elimination of cholesterol is increased (280). Thyroid hormones may occasionally, especially if associated with diarrhea, cause a marked increase in bile acid elimination (see Section VIIB), while nicotinic acid only occasionally augments fecal bile salt output (221, 281). Of the more recently developed absorbable hypolipidemic drugs, DH-581 appears to stimulate bile acid excretion at least transiently, probably by inhibiting intestinal bile acid reabsorption (282). 

Gustafsson et al. (22) studied the fecal excretion of cholic acid-i C metabolites in conventional and germfree rats. The mean daily excretion of labeled cholic acid and its metabolites was 18.9 mg/kg body weight for the conventional group and 8.2 mg/kg body weight for the germfree group. As mentioned above, their techniques would not uniformly label the bile acid pool however, their other techniques may have caused inclusion of the muricholic acids in their assay. 

Interpopulation studies have demonstrated considerable differences in the fecal concentrations of bile acids. Our own studies in nineteen populations[30] have revealed that subjects consuming a diet typical of a rural third world population excreted relatively low concentrations of bile acids when compared to subjects consuming a western style diet (Table 2). Bile acid degradation to secondary substrates is also apparently reduced in these third world groups consuming a low animal fat and protein diet which is also high in fiber. 

Partial summary of lipoprotein metabolism in humans. I to VII are sites of action of hypolipidemic drugs. I, stimulation of bile acid and/or cholesterol fecal excretion II, stimulation of lipoprotein lipase activity III, inhibition of VLDL production and secretion IV, inhibition of cholesterol biosynthesis V, stimulation of cholesterol secretion into bile fluid VI, stimulation of cholesterol conversion to bile acids VII, increased plasma clearance of LDL due either to increased LDL receptor activity or altered lipoprotein composition. CHOL, cholesterol IDL, intermediate-density lipoprotein. 

Another possible mechanism involves the effect of saponins on micelle formation. Saponins are known to alter the size or shape of micelles (Oakenfull, 1986 Oakenfull and Sidhu, 1983), an observation that is consistent with decreased bile acid absorption (Stark and Madar, 1993) and increased fecal bile acid excretion (Malinow et al., 1981 Nakamura et al.,1999). Saponins may also directly bind bile acids (Oakenfull and Sidhu, 1989), which would presumably interfere with micelle formation and decrease cholesterol absorption. Other studies have found that saponins decrease the absorption of fat-soluble vitamins (Jenkins and Atwal, 1994) and triglycerides (Han et al., 2002 Okuda and Han, 2001), indicating decreased micelle formation. However, direct evidence showing impaired micelle formation in vivo is lacking. Moreover, Harwood et al. (1993) reported no change in bile acid absorption or interruption of the enterohepatic circulation of bile acids in hamsters fed tiqueside, despite significant reductions in cholesterol absorption. 

The mass of bile acids per 0.5 g feces = mass in 1 ml methanol x dpm 14C-taurocholate added/dpm recovered in 1 ml methanol. As for neutral sterols, the total excreted per 3 days is calculated from the total fecal mass collected and data are reported as mass (or moles) excreted per day per gram body weight. 

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