Roles of ursodeoxycholic acid in the bile biochemistry and metabolomics in patients with choledocholithiasis: a prospective study

Abstract

Introduction: Recurrence after the endoscopic treatment of common bile duct stones (CBDS) is related to bile metabolism and bile compositions. Ursodeoxycholic acid (UDCA) has been proved effective in reducing the recurrence of CBDS. However, the detailed effects of UDCA on bile metabolism are still not extensively explored.

Objectives: This study aimed to analyze the role of UDCA in patients with choledocholithiasis (CDC) from the perspective of biochemistry and metabolomics.

Methods: A total of 89 patients with CDC who underwent endoscopic retrograde cholangiopancreatography were prospectively examined and randomly assigned to control and UDCA groups. The biochemical detections (cholesterol, bilirubin, and so on) were performed on the collected bile. Moreover, the metabolomics analysis was conducted based on bile from 20 patients in the UDCA group.

Results: The bile levels of cholesterol and endotoxins significantly decreased after UDCA treatment. Regarding bile metabolomics, the levels of 25 metabolites changed significantly after UDCA treatment. The pathway enrichment analysis showed that the UDCA addition evoked a common response related to phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; arachidonic acid metabolism; and terpenoid backbone biosynthesis.

Conclusions: UDCA treatment within a short time interval (7 days) did not improve the circulating laboratory values in patients with CDC who had undergone endoscopy surgery. However, relevant decreases in the bile levels of cholesterol and endotoxin were observed. UDCA evoked a common response related to lipid metabolism and amino acid metabolism, which probably reduced the bile level of cholesterol, protected hepatocytes, and corrected the abnormality of lipid metabolism caused by CDC.

Keywords: Cholesterol; Common bile duct stones; Endoscopic retrograde cholangiopancreatography; Liquid chromatography-mass spectrometry metabolomics; Ursodeoxycholic acid.