Biliary bile acid

Trautwein, E. A., Rieckhoff, D., Kunath-Rau, A., and Erbersdobler, H. F. (1998). Psyllium, not pectin or guar gum, alters lipoprotein and biliary bile acid composition and fecal sterol excretion in the hamster. Lipids 33, 573-582. 

Samples of gallbladder bile obtained in this way were analysed for bile acids, phospholipids and cholesterol (from which the cholesterol saturation indices were derived). Biliary bile-acid composition was then measured by HPLC. The vesicles were separated from micelles by sucrose density gradient ultra-centrifugation and the cholesterol microcrystal nucleation time measured as described above. 

Trautwein, E.A., Rieckhoff, D., and Erbersdobler, H.F. 1998. Dietary inulin lowers plasma cholesterol and triacylglycerol and alters biliary bile acid profile in hamsters. J. Nutr. 128, 1937-1943. Trautwein, E.A., Duchateau, G. S. M. J.E., Lin, Y., Molhuizen, S.M., Mel nikov, H. O. F., and Ntanios, F.Y. 2003. Proposed mechanisms of cholesterol lowering action of plant sterols. Eur. 

Batta, A.K., Salen, G., Mirchandani, R., Tint, G.S., Shefer, S., Batta, M., Abroon, J., O Brien, C.B., Senior, J.R. Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis. Amer. J. Gastroenterol. 1993 88 691 -700... 

MacDonald, I. A., Williams, C. N., and Musial, B. C., 3a,7a, and 12a-hydroxy group specific enzymic analysis of biliary bile acids Comparison with gas-liquid chromatography. /. lipid Res. 20, 381-385 (1979). 

Although small amounts of the biliary bile acids, 3a,7 ,12a-trihydroxy- and 3a,la-dihydroxy-5)3-cholestan-26-oic acids, were detected, the major fecal bile acids were their 7-deoxy derivatives, 3 ,12 -dihydroxy- and 3a-hydroxy-5 8-cholestan-26-oic acids. Small amounts of 3j8,7a,12a-trihydroxy-5 -cholestan-26-oic acid, 3a,7 -, 3j8,7 -and 3jS,12a-dihydroxy-5)S-cholestan-26-oic acids, and 3 8-hydroxy-5j3-cholestan-26-oic acid were found as well [75]. Since intestinal bacterial in mammals are known to 7a-dehydroxylate C24 bile acids and to interconvert a- and j8-hydroxyl groups (Chapter 12), these C27 bile acids may be products of the intestinal flora in the alligator. 

The hydrolysis of bile acid conjugates is probably the initial reaction catalyzed by intestinal bacteria. Therefore, primarily free bile acids are isolated from the feces of man and animals [1-5]. The bulk of the free bile acids in feces of man is deoxycholic acid and lithocholic acid which are generated by the 7 -dehydroxylation of cholic acid and chenodeoxycholic acid, respectively. A portion of fecal acids is absorbed from the intestinal tract, returned to the liver where they are conjugated and again secreted via biliary bile. Therefore, the final composition of biliary bile acids is the result of a complex interaction between liver enzymes and enzymes in intestinal bacteria. 

Chen, W-J.L. Anderson, J.W. Biliary bile acid and lipid metabolism of oat bran. Fed. Proc. 41 399, 1982. 

Bile salts appear to have a central role in the biliary secretion of water and solutes (103,104). Thus about half of biliary water secretion is bile acid dependent and the other half bile acid independent (104,105). In addition, cholesterol and lecithin secretion is also, at least in part, bile acid dependent. Feeding of bile acids to patients with interrupted enterohepatic circulation has a normalizing effect on the biliary secretion of bile acids, cholesterol and lecithin, so that despite an augmented cholesterol output its solubilization is improved (106,107). When the variation in the biliary bile acid secretion... 

The most striking initial change in biliary obstruction is a decrease or complete stopping of biliary bile acid secretion, which explains the reduction... 

Since, in the rat, cholesterol is eliminated largely in the form of bile acids, it was expected that bile acid secretion in bile would be increased in the hyperthyroid state. Early experiments to test this point indicated that biliary bile acid secretion was actually normal or below normal (2,3). These results can be explained in terms of the inadequate analytical procedures then in use. Only cholate secretion was measured, and the levels of cheno-deoxycholate were not taken into account. When both of these bile acids were determined, it was shown that, in the bile fistula rat, the total production of bile acids was about the same in the hyperthyroid as in the euthyroid state, and lower in the hypothyroid state (4). In addition, in the hyperthyroid state, the normal ratio of cholate/chenodeoxycholate was reversed from approximately 3 1 to 1 3—cholic acid synthesis was decreased, and chenodeoxycholic acid synthesis was increased two- to threefold (4). Identical results were obtained in the bile fistula rat treated with noncalorigenic doses of D-tri-iodothyronine (5,6), suggesting that these effects are not necessarily a function of the basal metabolic rate. 

Norman (3) demonstrated that the types of bile acids found in normal rat bile were not the same as those which were excreted in the feces. However, when the rats were fed high levels of antibiotics, the fecal bile acids were excreted essentially unchanged from the biliary bile acids (4). The intestinal bacteria were responsible for the hydrolysis of the biliary taurine-conjugated bile acids to the free bile acids found in the feces. Norman also showed that the dehydroxylation of cholic acid to deoxycholic acid could be prevented by Inhibiting the intestinal bacteria. The total amount of fecal bile acid excreted by conventional chicks has been found to be significantly lowered (5) by incorporation of an antibiotic into the diet. 

As will be discussed below, the fecal bile acid excretion of germfree subjects is only one-half that of comparable conventional subjects. Wost-mann (unpublished data) has observed that the biliary bile acid flow in the germfree rat was three times greater than in the conventional rat. Since the pool sizes were essentially similar (22), this implies that the absorptive capacity and the number of cycles through the enterohepatic system were markedly greater in germfree rats than in conventional rats. 

The biliary bile acids of germfree chicks have been shown by Haslewood (34) to be composed of approximately 80% taurochenodeoxycholic acid, 17% taurocholic acid, and 5% tauroallocholic acid. 

Chijiiwa K, Miznta A, Ueda J, Takamatsu Y, Nakamura K, Watanahe M, Kuroki S, Tanaka M (2002) Relation of biliary bile acid output to hepatic adenosine triphosphate level and biliary indocyanine green excretion in humans. World J Surg 26,457-61. 

The 3a-, 7a-, and 12a-Hydroxy Group-Specific Enzyme Analysis of Biliary Bile Acids Comparison with Gas-Liquid Chromatography J. Lipid Res. 21(3) 381-385 (1980) ... 

This specifity for cholate or its conjugates on cholesterol absorption has also been demonstrated by modification of biliary bile acid composition by hormonal perturbations (see[40]). For example, in hypothyroid rats, there is a diminished biliary output of bile acids[41], and a shift in the ratio of biliary cholate and cheno-deoxycholate. This ratio is approximately 3 1 cholate to cheno-deoxycholate in normal rats and is shifted dramatically (9 1) in hypothyroid rats[42]. As might be expected, this hormonal deficiency results in multiple alterations in overall physiology, among which are hypercholesterolemia and increased absorbability of choles-terol[40]. Conversely, administration of thyroid hormones (L-thyroxine or triiodothyronine) results in diminished levels of biliary cholate, and proportional increases in chenodeoxycholate. 

Effects of dietary cholesterol and L-thyroxine on biliary bile acid composition and secretory rate, and on plasma, liver and bile cholesterol levels in rats, Endocrln.Jap., 17 107 (1970). 

For a given bile salt lecithin ratio the interfacial resistance decreases with increasing BS concentration and in the experience of Kwan and coworkers cheno-rich bile dissolves Ch three times as fast as bile with normal biliary bile acid composition. 

It has been shown that simultaneous infusion of taurocholic acid overcomes the cholestatic effect of lithocholic and taurolithocholic acid[2,32,33], possibly by micellar solubilization of the toxic molecules and promotion of their excretion into bile. Therefore, in situations that are characterized by low biliary bile acid output rates, the liver may be more susceptible to the hepatoxic action of monohydroxy bile acids. We studied the effects of endogenous bile acids on the cholestatic action of SGLC in rats. For this purpose we used an animal model in which the enterohepatic circulation (EHC) can be interrupted and restored without direct surgical intervention. 

Moreover, intraluminal bile acid (BA) concentration can be lower than normal in patients with CF[4], as a consequence of persistent BA malabsorption, further abetting their maldigestion. In fact, increased fecal BA losses have been repeatedly reported to occur in CF patients with pancreatic insufficiency[5,6,7] and can produce other important clinical consequences. There may be a contraction of bile acid pool size, as the capacity of the liver to compensate these losses becomes insufficient[8]. Biliary bile acid concentration... 

The biliary cholesterol specific activities (after administration of C H]-mevalonic acid) were the same in all groups, but biliary bile acid specific activity was higher in the control baboons than in test animals. These data, plus the higher primary/ secondary bile acid ratio observed in the test animals, suggest that reduced bile acid synthesis may be one cause of the hypercholesteremia observed in animals fed the semi-synthetic diets. 

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