Analysis of Serum Bile Acid Profile Characteristics and Identification of New Biomarkers in Lean Metabolic Dysfunction-Associated Fatty Liver Disease Based on LC-MS/MS

Abstract

Objectives: Plasma bile acid (BA) has been widely studied as pathophysiological factors in chronic liver disease. But the changes of plasma BA level in lean metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. Here, we clarified the BA metabolic characteristics of lean MAFLD and explored its significance and mechanism as a marker. Methods: We employed ultra-performance liquid chromatography tandem mass spectrometry based on BA metabonomics to characterize circulating bile acid in lean MAFLD patients. Explore its significance as serum biomarkers by further cluster analysis, functional enrichment analysis, and serum concentration change analysis of differential BAs. Evaluation of diagnostic value of differential BAs by ROC analysis. Results: A total of 65 BAs were detected and 17 BAs were identified which showed different expression in the lean-MAFLD group compared with the normal group. Functional annotation and enrichment analysis of KEGG and HMDB showed that differential BAs were mainly related to bile acid biosynthesis, bile secretion, cholesterol metabolism, and familial hypercholangitis, involving diseases including but not limited to cirrhosis, hepatocellular carcinoma, chronic active hepatitis, colorectal cancer, acute liver failure, and portal vein obstruction. ROC analysis displayed that the 6 BA metabolites (GCDCA-3S, GUDCA-3S, CDCA-3S, NCA, TCDCA, and HDCA) exhibited well differential diagnostic ability in discriminating between lean MAFLD patients and normal individuals with an area under the curve (AUC) ⩾0.85. Conclusions: We delineated the characteristics of BA level in patients with lean MAFLD, and identified 6 potential plasma BA biomarkers of lean MAFLD.