Wang Bing, Zhang Fei, Qiu Hong, He Yujie, Shi Haotian, Zhu Yuerong
Department of Clinical Laboratory, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Department of Stomatology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China.
Clin Med Insights Endocrinol Diabetes. 2024 Sep 22;17:11795514241282253. doi: 10.1177/11795514241282253. eCollection 2024.
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.
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.
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.
We delineated the characteristics of BA level in patients with lean MAFLD, and identified 6 potential plasma BA biomarkers of lean MAFLD.
血浆胆汁酸（BA）作为慢性肝病的病理生理因素已得到广泛研究。但瘦型代谢功能障碍相关脂肪性肝病（MAFLD）患者血浆BA水平的变化仍不清楚。在此，我们阐明了瘦型MAFLD的BA代谢特征，并探讨了其作为标志物的意义及机制。
我们采用基于BA代谢组学的超高效液相色谱串联质谱法来表征瘦型MAFLD患者的循环胆汁酸。通过进一步的聚类分析、功能富集分析以及差异BA的血清浓度变化分析，探索其作为血清生物标志物的意义。通过ROC分析评估差异BA的诊断价值。
共检测到65种BA，鉴定出17种BA，其在瘦型MAFLD组与正常组中表现出不同的表达。KEGG和HMDB的功能注释及富集分析表明，差异BA主要与胆汁酸生物合成、胆汁分泌、胆固醇代谢以及家族性肝内胆汁淤积症相关，涉及的疾病包括但不限于肝硬化、肝细胞癌、慢性活动性肝炎、结直肠癌、急性肝衰竭和门静脉阻塞。ROC分析显示，6种BA代谢物（甘氨鹅去氧胆酸 - 3S、甘氨熊去氧胆酸 - 3S、鹅去氧胆酸 - 3S、去氧胆酸、牛磺鹅去氧胆酸和猪去氧胆酸）在区分瘦型MAFLD患者和正常个体方面表现出良好的鉴别诊断能力，曲线下面积（AUC）⩾0.85。
我们描绘了瘦型MAFLD患者的BA水平特征，并鉴定出6种瘦型MAFLD潜在的血浆BA生物标志物。
