Assessment of Gall-Bladder Storage Function in Man

1983 ◽  
Vol 65 (2) ◽  
pp. 185-191 ◽  
Author(s):  
R. P. Jazrawi ◽  
R. M. Kupfer ◽  
C. Bridges ◽  
A. Joseph ◽  
T. C. Northfield
Keyword(s):  
Bile Acid ◽  
Gall Bladder ◽  
Bile Acids ◽  
Saturation Index ◽  
Biliary Lipid ◽  
Fasting State ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Lipid Mass

1. We have validated a scintiscanning method for measuring fasting-state gall-bladder (GB) filling in man. 99mTc-labelled diethyl phenylcarbamoylmethyliminodiacetate (Tc-HIDA) was given intravenously, and 90 min later GB and gut activity were measured by using two isosensitive rectilinear scanning heads (anterior and posterior). Studies with a phantom GB in vitro, and studies in man in vivo, showed that the maximum error due to differences in isotope depth was 8%, compared with 300% when only one head was used. 2. By combining this technique with measurement of biliary lipid concentrations of fasting-state GB bile obtained by nasoduodenal intubation and intravenous cholecystokinin infusion, we were able to measure for the first time the total mass of all three biliary lipids in the GB. GB bile samples obtained in this way were divided into three consecutive portions of equal size in order to assess GB mixing. Bile acid pool size was also measured by isotope dilution. 3. We studied 12 healthy non-obese men. Fasting-state GB filling over 90 min (mean ± sem) was 54 ±8%. Biliary lipid mass in GB was 4.9 ±0.5 mmol for bile acids (67 ± 5% of the total bile acid pool), 1.6 ±0.2 mmol for phospholipid and 0.5 ± 0.1 mmol for cholesterol. The three consecutive portions of fasting GB bile gave values of 1.05 ± 0.07, 1.05 ± 0.06 and 1.03 ±0.10 for cholesterol saturation index (SI) and 6.6 ±1.1, 7.4 ± 1.6 and 6.5 ± 1.0 for Tc-HIDA c.p.m. × 1000 per mmol of bile acids. 4. The SI of fasting-state GB bile was significantly correlated with fasting-state GB filling (r = 0.63; P < 0.05). It was also correlated with cholesterol mass in GB (r = 0.64; P < 0.05), but not with bile acid and phospholipid mass. 5. We conclude that: (a) valid measurements of GB filling can be made in man by a simple scintiscanning technique employing 99mTc-HIDA as a biliary marker; (b) biliary lipid mass can also be measured if GB bile is obtained; (c) SI in health is in part determined by the degree of fasting-state GB filling, and in part by cholesterol mass in GB; (d) fasting-state GB content is well mixed in health.

scholarly journals Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Tilman Sauerbruch ◽  
Martin Hennenberg ◽  
Jonel Trebicka ◽  
Ulrich Beuers
Keyword(s):  
Liver Cirrhosis ◽  
Bile Acid ◽  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Vascular Dysfunction ◽  
Farnesoid X Receptor ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Circulatory Disturbance

The bile acid pool with its individual bile acids (BA) is modulated in the enterohepatic circulation by the liver as the primary site of synthesis, the motility of the gallbladder and of the intestinal tract, as well as by bacterial enzymes in the intestine. The nuclear receptor farnesoid X receptor (FXR) and Gpbar1 (TGR5) are important set screws in this process. Bile acids have a vasodilatory effect, at least according to in vitro studies. The present review examines the question of the extent to which the increase in bile acids in plasma could be responsible for the hyperdynamic circulatory disturbance of liver cirrhosis and whether modulation of the bile acid pool, for example, via administration of ursodeoxycholic acid (UDCA) or via modulation of the dysbiosis present in liver cirrhosis could influence the hemodynamic disorder of liver cirrhosis. According to our analysis, the evidence for this is limited. Long-term studies on this question are lacking.

scholarly journals Biliary lipid composition in idiopathic bile acid malabsorption

Gut ◽  
1998 ◽  
Vol 43 (6) ◽  
pp. 812-816 ◽  
Author(s):  
M Fracchia ◽  
S Pellegrino ◽  
P Secreto ◽  
A Pera ◽  
G Galatola
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Lipid Composition ◽  
Chronic Diarrhoea ◽  
Biliary Lipid ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Bile Acid Malabsorption ◽  
Increased Risk ◽  
Biliary Lipid Composition

Background—Chronic diarrhoea is the clinical hallmark of patients presenting with idiopathic bile acid malabsorption. Its pathogenesis is unknown; colonic water secretion can be induced by dihydroxy bile acids, but it is not known whether enrichment of the bile acid pool with these bile acids occurs in such patients. Furthermore, bile acid malabsorption is known to affect biliary lipid composition, but no information is available for the idiopathic type.Aims—To verify: (a) whether diarrhoea in patients with idiopathic bile acid malabsorption is associated with enrichment of the bile acid pool with dihydroxy bile acids; and (b) whether supersaturation with cholesterol of duodenal bile occurs in such patients as a result of chronic bile acid depletion.Patients—Thirteen patients with idiopathic bile acid malabsorption diagnosed according to abnormal 75SeHCAT test and absence of other organic diseases, and 23 control subjects.Methods—Bile rich duodenal fluid was collected during intravenous ceruletide infusion in the fasting state. Biliary lipids were analysed by enzymatic assays and bile acids by high performance liquid chromatography.Results—Patients with idiopathic bile acid malabsorption had a cholesterol saturation index similar to controls. Bile acid composition showed only a decrease in percentage cholic acid (29 (2)% versus 36 (2)%; p<0.05); the dihydroxy:trihydroxy bile acid ratio was similar to controls.Conclusions—Patients with idiopathic bile acid malabsorption do not have an increased risk of forming cholesterol gallstones. The mechanism of diarrhoea does not seem to depend on an enrichment of the bile acid pool with dihydroxy bile acids.

Bile Acid Pool in the Rat: Bile Acids and Steroids. 78.

1960 ◽  
Vol 48 (3-4) ◽  
pp. 439-442 ◽  
Author(s):  
Sten Eriksson
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Rat Bile

scholarly journals Antibiotic-Induced Changes in Microbiome-Related Metabolites and Bile Acids in Rat Plasma

Metabolites ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 242
Author(s):  
Véronique de Bruijn ◽  
Christina Behr ◽  
Saskia Sperber ◽  
Tilmann Walk ◽  
Philipp Ternes ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Community Analysis ◽  
Rat Plasma ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Administration Routes ◽  
Plasma Metabolome ◽  
Induced Changes ◽  
Plasma Metabolite

Various environmental factors can alter the gut microbiome’s composition and functionality, and modulate host health. In this study, the effects of oral and parenteral administration of two poorly bioavailable antibiotics (i.e., vancomycin and streptomycin) on male Wistar Crl/Wi(Han) rats for 28 days were compared to distinguish between microbiome-derived or -associated and systemic changes in the plasma metabolome. The resulting changes in the plasma metabolome were compared to the effects of a third reference compound, roxithromycin, which is readily bioavailable. A community analysis revealed that the oral administration of vancomycin and roxithromycin in particular leads to an altered microbial population. Antibiotic-induced changes depending on the administration routes were observed in plasma metabolite levels. Indole-3-acetic acid (IAA) and hippuric acid (HA) were identified as key metabolites of microbiome modulation, with HA being the most sensitive. Even though large variations in the plasma bile acid pool between and within rats were observed, the change in microbiome community was observed to alter the composition of the bile acid pool, especially by an accumulation of taurine-conjugated primary bile acids. In-depth investigation of the relationship between microbiome variability and their functionality, with emphasis on the bile acid pool, will be necessary to better assess the potential adverseness of environmentally induced microbiome changes.

scholarly journals Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat

2008 ◽  
Vol 294 (4) ◽  
pp. G1009-G1016 ◽  
Author(s):  
Clavia Ruth Wooton-Kee ◽  
David E. Cohen ◽  
Mary Vore
Keyword(s):  
Bile Acid ◽  
Protein Expression ◽  
Mrna Expression ◽  
Bile Acids ◽  
Fold Increase ◽  
Bile Acid Pool ◽  
Hydrophobicity Index ◽  
Acid Pool ◽  
Bile Acid Transporters ◽  
Cholic Acids

Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [cholesterol 7α-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12α-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [postpartum (PP) days 10, 14, and 19–23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7α-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool.

scholarly journals A metabolic pathway for bile acid dehydroxylation by the gut microbiome

2019 ◽  
Author(s):  
Masanori Funabashi ◽  
Tyler L. Grove ◽  
Victoria Pascal ◽  
Yug Varma ◽  
Molly E. McFadden ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Lithocholic Acid ◽  
Primary Biliary Cholangitis ◽  
Bile Acid Pool ◽  
Secondary Bile Acid ◽  
Acid Pool ◽  
Road Map ◽  
Host Physiology

ABSTRACTThe gut microbiota synthesize hundreds of molecules, many of which are known to impact host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at ~500 μM and are known to block C. difficile growth1, promote hepatocellular carcinoma2, and modulate host metabolism via the GPCR TGR53. More broadly, DCA, LCA and their derivatives are a major component of the recirculating bile acid pool4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Despite the clear impact of DCA and LCA on host physiology, incomplete knowledge of their biosynthetic genes and a lack of genetic tools in their native producer limit our ability to modulate secondary bile acid levels in the host. Here, we complete the pathway to DCA/LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the 8-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a non-producing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool, and provide a road map for deorphaning and engineering pathways from the microbiome as a critical step toward controlling the metabolic output of the gut microbiota.

Bacterial deconjugation and enterohepatic circulation of norursocholic acid conjugates in rats

1991 ◽  
Vol 261 (6) ◽  
pp. G1065-G1071
Author(s):  
J. Lillienau ◽  
B. Borgstrom
Keyword(s):  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Cecal Content ◽  
Acid Biosynthesis ◽  
Bile Acid Pool ◽  
Distal Small Intestine ◽  
Acid Pool ◽  
System 2 ◽  
Small Intestinal

Experiments were performed to define the metabolism of norusocholic acid (nUC) conjugates and to quantify to what extent the bile acid pool can be enriched in these bile acids. In vitro incubations of norusocholylglycine (nUCG) and -taurine (nUCT) with small intestinal or cecal content showed deconjugation with only cecal content. Cholylglycine (CG) was deconjugated by small intestinal and cecal content. Infusion of nUCG and CG showed that only a small proportion of nUCG was deconjugated after 24 h of enterohepatic circulation, whereas all CG was deconjugated. When nUCT was administered orally, deconjugation was shown to take place mainly in the cecum. Chronic feeding of nUCT enriched the bile acid pool with only 20% nUCT. We conclude that nUC conjugates are deconjugated primarily by bacteria in the cecum and colon, in contrast to CG, which, in addition to cecum and colon, is deconjugated in the distal small intestine. nUCT and its metabolites do not enrich in the circulating bile acid pool mainly for the following reasons: 1) nUC conjugates have a low affinity for the ileal transport system; 2) nUC, even if formed by deconjugation, is not passively absorbed at a sufficient rate; 3) the small amount of norursodeoxycholic acid formed from nUC is glucuronidated in the liver and glucuronide conjugates do not undergo enterohepatic circulation; and 4) nUC conjugates do not suppress bile acid biosynthesis.

Differing effects of hydroxy-7-oxotaurine-conjugated bile acids on bile flow and biliary lipid secretion in dogs

1984 ◽  
Vol 246 (2) ◽  
pp. G166-G172
Author(s):  
R. G. Danzinger ◽  
M. Nakagaki ◽  
A. F. Hofmann ◽  
E. B. Ljungwe
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Critical Micellar Concentration ◽  
Independent Effect ◽  
Biliary Lipid ◽  
Compound I ◽  
Lipid Secretion ◽  
The Individual

The effects on bile flow and biliary lipid secretion of two taurine-conjugated 7-oxo bile acids, 3 alpha-hydroxy-7-oxocholanoyltaurine (I) and 3 alpha,12 alpha-dihydroxy-7-oxocholanoyltaurine (II), were measured in the unanesthetized, chronic bile fistula dog. Each synthetically prepared compound, or cholyltaurine as control, was infused intravenously at a physiological rate of 1 mumol X kg-1 X min-1 for randomized 90-min periods. Bile samples were collected and analyzed for biliary lipids (bile acids, phospholipid, and cholesterol) and bile acid composition. Both compounds were secreted efficiently in bile, recovery averaging 90%. The trisubstituted compound (II) induced a greater choleresis and less phospholipid and cholesterol secretion than the disubstituted compound (I) or cholyltaurine. Each oxo compound was partially reduced during hepatic passage: about 47% of I (to mostly chenodeoxycholyltaurine) and about 30% of II (to mostly cholyltaurine). The effect of the individual bile acids on biliary lipid secretion was then calculated by assuming that a) the infused bile acid induced biliary lipid secretion after its hepatic biotransformation and b) each bile acid or its biotransformation product exerted an independent effect on biliary lipid secretion (expressed as a linkage coefficient, e.g., phospholipid secretion/bile acid secretion). For phospholipid, the calculated linkage coefficient for I was 0.31; for II, 0.07. For cholesterol, the calculated linkage coefficient for I was 0.014; for II, 0.003. In vitro studies indicated that the critical micellar concentration (CMC) in 0.15 M Na+ was 22 mM for I and 40 mM for II (compared with 6 mM for cholyltaurine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholestasis induced by Sulphated Glycolithocholic Acid in the Rat: Protection by Endogenous Bile Acids

1985 ◽  
Vol 68 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Folkert Kuipers ◽  
Rick Havinga ◽  
Roel J. Vonk
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Biliary Excretion ◽  
Hepatic Clearance ◽  
Recovery Phase ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Hepatotoxic Effect ◽  
Biliary Excretion Rate ◽  
Bile Production

1. Sulphated glycolithocholic acid (SGLC) causes cholestasis in experimental animals, despite its sulphated form. In the present study, the cholestatic potency and the pharmacokinetics of SGLC were investigated in rats under two conditions: (a) in the presence of an intact circulating bile acid pool and (b) after exhaustion of the bile acid pool by 24 h of bile diversion. 2. Intravenous administration of SGLC (8 μmol/ 100 g body weight) to rats with an intact bile acid pool did not cause cholestasis. However, biliary phospholipid and cholesterol concentrations were reduced by 40% and 29% respectively during the first hour after administration. When the same dose of the bile acid was injected in rats with a 24 h biliary drainage, a complete cessation of bile production was observed within 1 h. Twelve hours after the onset of cholestasis, bile production gradually increased again, showed a marked overshoot, and reached control levels after 3 days. In the recovery phase, biliary phospholipid and cholesterol concentrations were greatly reduced. 3. The absence of endogenous bile acids did not change the hepatic clearance rate of a tracer dose of radiolabelled SGLC, but markedly decreased its biliary excretion rate. 4. It was concluded that the hepatotoxic effect of SGLC is much more pronounced in rats with an exhausted bile acid pool, possibly due to a slower biliary excretion of the toxic compound. This phenomenon may have clinical implications for patients with a contracted bile acid pool.

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