The profile of bile acids and their sulfate metabolites in human urine and serum

Bathena, Sai Praneeth Reddy; Mukherjee, Sandeep; Olivera, Marco; Alnouti, Yazen

doi:10.1016/j.jchromb.2013.10.019

Cited by 106 publications

(153 citation statements)

References 67 publications

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“…[15][16][17] Within the past decade, LC-MS has been heavily utilized for the separation and detection of BAs in human and animal model biofluid samples. 9,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] The most comprehensive of these methods have a relatively long analytical cycle (> 30 minutes), precluding rapid sample analysis. 21,25,28,30,34 On the other hand, the most rapid methods (< 10 minutes) have limited BA coverage.…”

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confidence: 99%

“…19,33 The majority of separations have analytical times greater than 20 minutes and intermediate level of BA species coverage (ranging from 11 to 32 species monitored). 9,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Very few LC-MS methods report coverage of tertiary BAs such as sulfate conjugates which have recently been implicated in the important role of the gut microbiota in human metabolism. 9,32,[34][35][36] The analytical foundation of these methods is reversed-phase separation utilizing a C 18 stationary phase, which is suitable for retention and separation of the diverse range of hydrophobicity present among BAs.…”

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confidence: 99%

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Bile Acid Profiling and Quantification in Biofluids Using Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

et al. 2015

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Bile acids are important end products of cholesterol metabolism. While they have been identified as key factors in lipid emulsification and absorption due to their detergent properties, bile acids have also been shown to act as signaling molecules and intermediates between the host and the gut microbiota. To further the investigation of bile acid functions in humans, an advanced platform for high throughput analysis is essential. Herein, we describe the development and application of a 15 min UPLC procedure for the separation of bile acid species from human biofluid samples requiring minimal sample preparation. High resolution time-of-flight mass spectrometry was applied for profiling applications, elucidating rich bile acid profiles in both normal and disease state plasma. In parallel, a second mode of detection was developed utilizing tandem mass spectrometry for sensitive and quantitative targeted analysis of 145 bile acid (BA) species including primary, secondary, and tertiary bile acids. The latter system was validated by testing the linearity (lower limit of quantification, LLOQ, 0.25?10 nM and upper limit of quantification, ULOQ, 2.5?5 ?M), precision (?6.5%), and accuracy (81.2?118.9%) on inter- and intraday analysis achieving good recovery of bile acids (serum/plasma 88% and urine 93%). The ultra performance liquid chromatography?mass spectrometry (UPLC-MS)/MS targeted method was successfully applied to plasma, serum, and urine samples in order to compare the bile acid pool compositional difference between preprandial and postprandial states, demonstrating the utility of such analysis on human biofluids

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Bile Acid Profiling and Quantification in Biofluids Using Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

et al. 2015

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“…In humans, almost half of the lithocholic acid (LCA) secreted into bile is present in divalent, sulfated, and amidated form (4), and bile acid sulfates comprise a large proportion of the bile acids excreted in urine (5). Sulfonation is not specific to LCA because sulfated forms of cholic acid, deoxycholic acid, chenodeoxycholic acid, and ursodeoxycholic acid are also found in serum and urine, usually as double-conjugates with glycine and taurine in the side-chain (6). Notably, the levels of bile acid sulfates are elevated in physiological and pathophysiological cholestasis (7,8).…”

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“…Bile acids are primarily mono-sulfated in humans (although traces of disulfates are found in urine, possibly through renal sulfation) and in mice. However, the location of the sulfate group on the bile acid steroid nucleus differs, preferentially occurring at the C-3 position in humans and at the C-7 position in mice (with the exception of LCA, which is a minor bile acid in mice) (3,6,12). This is important because the sulfate moiety's position has a profound effect on the physiological behavior of bile acids.…”

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Will the real bile acid sulfotransferase please stand up? Identification of Sult2a8 as a major hepatic bile acid sulfonating enzyme in mice

Dawson

Setchell

2017

Journal of Lipid Research

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“…Some research has been conducted to determine whether BA concentrations might be useful to differentiate various liver diseases (Bathena et al, 2013). It has generally been thought that an increase in BAs in serum is secondary to high BA concentrations in liver, due to a decrease in uptake of BAs into liver, or an increased retro-transport of BAs from liver to serum to protect the liver from BA-induced toxicity.…”

Section: Discussionmentioning

confidence: 99%

Decreased Bile-Acid Synthesis in Livers of Hepatocyte-Conditional NADPH–Cytochrome P450 Reductase–Null Mice Results in Increased Bile Acids in Serum

Cheng

Zhang

Klaassen

2014

J Pharmacol Exp Ther

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NADPH-cytochrome P450 reductase (Cpr) is essential for the function of microsomal cytochrome P450 monooxygenases (P450), including those P450s involved in bile acid (BA) synthesis. Mice with hepatocyte-specific deletion of NADPH-cytochrome P450 reductase (H-Cpr-null) have been engineered to understand the in vivo function of hepatic P450s in the metabolism of xenobiotics and endogenous compounds. However, the impact of hepatic Cpr on BA homeostasis is not clear. The present study revealed that H-Cpr-null mice had a 60% decrease in total BA concentration in liver, whereas the total BA concentration in serum was almost doubled. The decreased level of cholic acid (CA) in both serum and livers of H-Cpr-null mice is likely due to diminished enzyme activity of Cyp8b1 that is essential for CA biosynthesis. Feedback mechanisms responsible for the reduced liver BA concentrations and/or increased serum BA concentrations in H-Cpr-null mice included the following: 1) enhanced alternative BA synthesis pathway, as evidenced by the fact that classic BA synthesis is diminished but chenodeoxycholic acid still increases in both serum and livers of H-Cpr-null mice; 2) inhibition of farnesoid X receptor activation, which increased the mRNA of Cyp7a1 and 8b1; 3) induction of intestinal BA transporters to facilitate BA absorption from the intestine to the circulation; 4) induction of hepatic multidrug resistance-associated protein transporters to increase BA efflux from the liver to blood; and 5) increased generation of secondary BAs. In summary, the present study reveals an important contribution of the alternative BA synthesis pathway and BA transporters in regulating BA concentrations in H-Cpr-null mice.

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The profile of bile acids and their sulfate metabolites in human urine and serum

Cited by 106 publications

References 67 publications

Bile Acid Profiling and Quantification in Biofluids Using Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

Bile Acid Profiling and Quantification in Biofluids Using Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

Will the real bile acid sulfotransferase please stand up? Identification of Sult2a8 as a major hepatic bile acid sulfonating enzyme in mice

Decreased Bile-Acid Synthesis in Livers of Hepatocyte-Conditional NADPH–Cytochrome P450 Reductase–Null Mice Results in Increased Bile Acids in Serum

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