Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones: From analytical method development towards application to clinical samples

Bile acids (BAs) are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps (CGP) and cholesterol gallstones (CGS). To date, there is neither systematic study on BAs profile of CGP or CGS, nor the relationship between them. To explore the metabolomics profile of plasma BAs in healthy volunteers, CGP and CGS patients, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma. The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples. The results show that, compared to healthy volunteers, CGP and CGS were both characterized by the significant decrease in plasma BAs pool size, furthermore CGP and CGS shared aberrant BAs metabolic characteristics. Chenodeoxycholic acid, glycochenodeoxycholic acid, λ-muricholic acid, deoxycholic acid, and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases. Subsequent analysis showed that clinical characteristics including cysteine, ornithine and body mass index might be closely related to metabolisms of certain BA modules. This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.