Detection technologies and metabolic profiling of bile acids: a comprehensive review

Abstract

Bile acids (BAs) are important regulatory factors of life activities, which are involved in the regulation of glucose, lipid and energy metabolisms, and closely associated with intestinal hormones, microbiotas and energy balance. BAs abnormalities easily lead to inflammation and metabolic diseases, in turn, the progress of diseases could influence characteristics of BAs. Therefore, accurate detection of BAs contents is of great significance to disease prevention, diagnosis and treatment. At present, the most widely used enzymatic method in clinical practice is applicable to the detection of total bile acid (TBA). In laboratory research, different types of BAs can be accurately separated and quantified by liquid chromatography-mass spectrometry (LC-MS). The metabolic profiling of BAs based on detection technologies can completely and accurately monitor their types and contents, playing a crucial role in disease prevention, diagnosis and treatment. We herein reviewed the main detection technologies of BAs and the application of metabolic profiling in related diseases in recent years.

Keywords: Bile acids; Detection technologies; Liquid chromatography-mass spectrometry; Metabolic disease; Metabolic profiling.

Fig. 1

Synthesis and metabolism of common bile acids in human. Two major biosynthetic pathways of bile acids are shown. The classic pathway accounts for over 90% of total bile acids in human. Cholesterol is converted to 7α-hydroxycholesterol by rate-limiting enzyme CYP7A1. Then 7α-hydroxycholesterol is converted to 7a-hydroxy-4-cholesten-3-one (C4) by HSD3B7. Under CYP8B1 and CYP27A1, C4 is converted to CA, and without CYP8B1, C4 is eventually converted to CDCA. In the alternative pathway, cholesterol is first converted to 27-hydroxycholesterol by CYP27A1, and then converted to 3β, 7α-dihydroxy-5-cholestenoic acid by CYP7B1. 3β, 7α-dihydroxy-5-cholestenoic acid is eventually converted to CDCA through a series of reactions. In intestine, CA and CDCA are converted to DCA and LCA through microbiota. About 95% of bile acids are reabsorbed in the intestine and transported back to the liver. This is called the enterohepatic circulation of bile acids. About 5% of the BAs pool is excreted with feces in a day

Fig. 2

Chemical structure monomer, glycine and taurine conjugates, and sulfated compound of common bile acids [, , , , –103]