Bile Acids Conjugation in Human Bile Is Not Random: New Insights from ¹H‐NMR Spectroscopy at 800 MHz

Abstract

Bile acids constitute a group of structurally closely related molecules and represent the most abundant constituents of human bile. Investigations of bile acids have garnered increased interest owing to their recently discovered additional biological functions including their role as signaling molecules that govern glucose, fat and energy metabolism. Recent NMR methodological developments have enabled single-step analysis of several highly abundant and common glycine- and taurine- conjugated bile acids, such as glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid. Investigation of these conjugated bile acids in human bile employing high field (800 MHz) 1H-NMR spectroscopy reveals that the ratios between two glycine-conjugated bile acids and their taurine counterparts correlate positively (R2 = 0.83–0.97; p = 0.001 × 10−2–0.006 × 10−7) as do the ratios between a glycine-conjugated bile acid and its taurine counterpart (R2 = 0.92–0.95; p = 0.004 × 10−3–0.002 × 10−10). Using such correlations, concentration of individual bile acids in each sample could be predicted in good agreement with the experimentally determined values. These insights into the pattern of bile acid conjugation in human bile between glycine and taurine promise useful clues to the mechanism of bile acids’ biosynthesis, conjugation and enterohepatic circulation, and may improve our understanding of the role of individual conjugated bile acids in health and disease.

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

“…The beneficial aspects of taurine conjugated BAs are reported in the literature (Hirano et al , 2006; Seyhun et al , 2011) along with the exploration of taurine as a potential therapeutic in human NAFLD (Gentile et al , 2011). Composition patterns of BAs in human bile among different states of liver disease also demonstrate a coordinated pattern of change among glycine and taurine conjugated BAs (Nagana et al , 2009) which also support our findings of altered BA composition and increased levels of conjugated BAs in the NASH hepatic samples.…”

Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach

“…BAs, key molecules for dietary fat handling, are mostly conjugated with the aminoacids glycine and taurine. Alterations in BA pool size and composition have been reported in hepatopancreatobiliary diseases [10][11][12][13]. Among biliary phospholipids, the most abundant species (>95%) are phosphatidylcholines (PCs), a broad family of diacylphospholipids with different fatty acid side chains [14,15], while sphyngomyelins (SMs) comprise about 1-3% of total phospholipids [16,17].…”

“…Taking advantage of this possibility, over the past years a number of studies have performed metabolomic and proteomic analyses of bile obtained from patients with biliary obstruction. Significant alterations in biliary lipid composition, including concentrations of PCs and conjugated BAs [11][12][13]15,19,35,36] or the presence of certain PC oxidized species, could discriminate malignant from benign biliary strictures [37]. Proteomic studies have significantly contributed to the definition of the normal bile composition, adding hundreds of new proteins to the list [22,[38][39][40][41][42][43][44].…”

Bile salts in digestion and transport of lipids

“…The process of conjugation decreases the hydrophobicity of BA, as shown in Table 1. A change in the ratio of glycine and taurine (normally 3:1) conjugation may be considered an indicator of liver disease [9,10], however it may also change with diet [11]. The decreased hydrophobicity, as well as the lower pKa of the BA, limits re-adsorption of the BA (Boyer, 2013).…”