Bile Acid Sulfation: A Pathway of Bile Acid Elimination and Detoxification

Alnouti, Yazen

doi:10.1093/toxsci/kfn268

Cited by 328 publications

(295 citation statements)

References 297 publications

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“…2A). SULT2A1 catalyzes the formation of BA sulfates within enterocytes (Alnouti, 2009). We speculate that reduced ASBT levels lead to diminished intracellular amounts of BA; compensation for this reduces BA sulphation and BA apical efflux.…”

Section: Discussionmentioning

confidence: 85%

Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression

et al. 2014

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The enterohepatic circulation of bile acids (BAs) critically depends on absorption of BA in the terminal ileum and colon, which can be affected by inflammatory bowel disease (IBD). Diarrhea in IBD is believed to result in part from BA malabsorption (BAM). We explored whether IBD alters mRNA expression of key intestinal BA transporters, BA detoxifying systems, and nuclear receptors that regulate BA transport and detoxification. Using real-time polymerase chain reaction, mucosal biopsy specimens from the terminal ileum in Crohn's disease (CD) patients and from the descending colon in ulcerative colitis (UC) patients were assessed for mRNA expression. Levels were compared with healthy controls. The main ileal BA uptake transporter, the apical sodium dependent bile acid transporter, was downregulated in active CD and UC and in CD in remission. Other significant changes such as repression of breast cancer-related protein and sulphotransferase 2A1 were seen only during active disease. In UC, pancolitis (but not exclusively left-sided colitis) was associated with altered expression of major BA transporters [multidrug resistance-associated protein 3 (MRP3), MRP4, multidrug resistance gene 1, organic solute transporter a/b] and nuclear receptors (pregnane X receptor, vitamin D receptor) in the descending colon. UC pancolitis leads to broad changes and CD ileitis to selective changes in intestinal BA transporter expression. Early medical manipulation of intestinal BA transporters may help prevent BAM.

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Section: Discussionmentioning

confidence: 85%

Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression

et al. 2014

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“…The elution order observed in the reversed-phase HPLC separation of monosulfated BAs was used to determine the sulfate position, as previously reported (C3 < C6 < C7 < C12). 49 Poly-sulfated BA products, however, were not observed. As previous studies have shown that liver sulfatase does not allow poly sulfation of BAs, their synthesis was not pursued.…”

Section: Resultsmentioning

confidence: 93%

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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“…Secretion into the systemic circulation is the only alternative route to transport hepatic bile salts. Although bile salts are often sulfated before urinary excretion in mammals with biliary atresia and other forms of cholestasis (33), renal excretion of bile salts in parasitic sea lamprey is highly unlikely because it must minimize or stop urine production to retain water in the hyperosmotic ocean. We found that bile salt production in liver remained minimal during parasitic stage (Figs.…”

Section: Resultsmentioning

confidence: 99%

Intestinal synthesis and secretion of bile salts as an adaptation to developmental biliary atresia in the sea lamprey

Yeh

Chung-Davidson

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Bile salt synthesis is a specialized liver function in vertebrates. Bile salts play diverse roles in digestion and signaling, and their homeostasis is maintained by controlling input (biosynthesis) and intestinal conservation. Patients with biliary atresia (i.e., obliteration of the biliary tree) suffer liver fibrosis and cirrhosis. In contrast, sea lamprey thrives despite developmental biliary atresia. We discovered that the sea lamprey adapts to biliary atresia through a unique mechanism of de novo synthesis and secretion of bile salts in intestine after developmental biliary atresia, in addition to known mechanisms, such as the reduction of bile salt synthesis in liver. During and after developmental biliary atresia, expression of cyp7a1 in intestine increased by more than 100-fold ( P < 0.001), whereas in liver it decreased by the same magnitude ( P < 0.001). Concurrently, bile salt pools changed in similar patterns and magnitudes in these two organs and the composition shifted from C24 bile alcohol sulfates to taurine-conjugated C24 bile acids. In addition, both in vivo and ex vivo experiments showed that aductular sea lamprey secreted taurocholic acid into its intestinal lumen. Our results indicate that the sea lamprey, a jawless vertebrate, may be in an evolutionarily transitional state where bile salt synthesis occurs in both liver and intestine. Understanding the molecular basis of these mechanisms may shed light on the evolution of bile salt synthesis and possible therapy for infant biliary atresia.

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Bile Acid Sulfation: A Pathway of Bile Acid Elimination and Detoxification

Cited by 328 publications

References 297 publications

Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression

Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression

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

Intestinal synthesis and secretion of bile salts as an adaptation to developmental biliary atresia in the sea lamprey

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