Profiling of Serum Bile Acids in a Healthy Chinese Population Using UPLC–MS/MS

Abstract

Bile acids (BAs) are a group of important physiological agents for cholesterol metabolism, intestinal nutrient absorption, and biliary secretion of lipids, toxic metabolites, and xenobiotics. Extensive research in the last two decades has unveiled new functions of BAs as signaling molecules and metabolic regulators that modulate hepatic lipid, glucose, and energy homeostasis through the activation of nuclear receptors and G-protein-coupled receptor signaling in gut-liver metabolic axis involving host-gut microbial co-metabolism. Therefore, investigation of serum BA profiles, in healthy human male and female subjects with a wide range of age and body mass index (BMI), will provide important baseline information on the BA physiology as well as metabolic homeostasis among human subjects that are regulated by two sets of genome, host genome, and symbiotic microbiome. Previous reports on age- or gender-related changes on BA profiles in animals and human showed inconsistent results, and the information acquired from various studies was highly fragmentary. Here we profiled the serum BAs in a large population of healthy participants (n = 502) and examined the impact of age, gender, and BMI on serum BA concentrations and compositions using a targeted metabonomics approach with ultraperformance liquid chromatography triple-quadrupole mass spectrometry. We found that the BA profiles were dependent on gender, age, and BMI among study subjects. The total BAs were significantly higher in males than in females (p < 0.05) and higher in obese females than in lean females (p < 0.05). The difference in BA profiles between male and female subjects was decreased at age of 50-70 years, while the difference in BA profiles between lean and obese increased for subjects aged 50-70 years. The study provides a comprehensive understanding of the BA profiles in healthy subjects and highlights the need to take into account age, gender, and BMI differences when investigating pathophysiological changes of BAs resulting from gastrointestinal diseases.

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

“…We found large variations in fasting BA concentrations both within and between individuals, as depicted in Figure 1. This is in line with studies of non-bariatric subjects, which found large diurnal variations within individuals [41,42] and large variations in production and concentrations between individuals [43,44].…”

Chenodeoxycholic Acid as a Potential Prognostic Marker for Roux-en-Y Gastric Bypass in Chinese Obese Patients

“…A total of 26 BAs analysis was performed using an established method modified for application to human serum (16). Briefly, an internal standard solution containing 0.1 M d4-CA, d4-UDCA and d4-LCA (C/D/N Isotopes, Quebec, Canada) was added to serum or standard solution includes 26 BAs.…”

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

“…[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.…”

“…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.…”