Department of Integrated Traditional and Western Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Henan Province Research Center for Kidney Disease, Zhengzhou, 450052, China.
Nutr Diabetes. 2024 Oct 9;14(1):85. doi: 10.1038/s41387-024-00315-0.
Diabetic kidney disease (DKD) is the major complication of diabetes concomitant with gut dysbiosis and glycometabolic disorder, which are strongly associated with bile acid (BA) metabolism. Yet studies investigating the BA metabolism involving in DKD pathogenesis are limited. This study aimed to explore the metabolomic profiling of BAs in DKD and analyze its association with DKD progression.
An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to quantify BAs in the plasma, fecal and urine samples of patients with DKD or T2DM and healthy individuals (n = 30 for each group). The key BAs associated with DKD were identified by orthogonal partial least-squares discriminant analysis (OPLS-DA) and receiver-operating characteristic (ROC) curve. Polynomial regression and Pearson's correlation analyses were performed to assess the correlation between the key BAs and the clinical indicators reflecting DKD progression.
Metabolomic profiling of 50 kinds of BAs presented the markedly step-wise alterations of BAs in plasma and feces as well as the little in urine of patients with DKD. Eight kinds of BAs in the plasma, eight kinds in the feces and three kinds in the urine were abnormally expressed, accompanying with the increased conjugated/unconjugated ratios of cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid and hyocholic acid in the plasma, and of cholic acid, chenodeoxycholic acid and lithocholic acid in the feces. Moreover, the increased plasma level of glycochenodeoxycholic acid, and the increased fecal levels of glycolithocholic acid, 7-ketodeoxycholic acid and chenodeoxycholic acid-3-β-D-glucuronide are strongly correlated with the clinical indicators reflecting DKD progression, including eGFR, 24 h urinary protein and 24 h urinary microalbumin.
Our study for the first time disclosed the specific alterations of BA metabolism reflecting the step-wise progression of DKD, providing the basis for early identification and therapeutical strategies for DKD.
糖尿病肾病（DKD）是糖尿病的主要并发症，与肠道菌群失调和糖代谢紊乱有关，而这些又与胆汁酸（BA）代谢密切相关。然而，关于胆汁酸代谢参与 DKD 发病机制的研究还很有限。本研究旨在探索 DKD 患者胆汁酸代谢组学特征，并分析其与 DKD 进展的关系。
采用超高效液相色谱串联质谱（UPLC-MS/MS）法测定 DKD 患者和 T2DM 患者及健康对照者（每组 30 例）的血浆、粪便和尿液中胆汁酸的含量。采用正交偏最小二乘判别分析（OPLS-DA）和受试者工作特征（ROC）曲线识别与 DKD 相关的关键胆汁酸。采用多项式回归和 Pearson 相关分析评估关键胆汁酸与反映 DKD 进展的临床指标之间的相关性。
胆汁酸代谢组学分析显示，DKD 患者的血浆和粪便中胆汁酸的水平呈现明显的逐步变化，而尿液中的变化较小。血浆中有 8 种胆汁酸、粪便中有 8 种胆汁酸和尿液中有 3 种胆汁酸异常表达，伴有血浆中胆酸、脱氧胆酸、鹅去氧胆酸、熊去氧胆酸和去氢胆酸的结合型/非结合型比值增加，以及粪便中胆酸、鹅去氧胆酸和石胆酸的比值增加。此外，血浆中甘氨鹅去氧胆酸水平的升高，粪便中甘氨胆酸、7-酮脱氧胆酸和鹅去氧胆酸-3-β-D-葡糖苷酸水平的升高与反映 DKD 进展的临床指标（包括 eGFR、24 小时尿蛋白和 24 小时尿微量白蛋白）密切相关。
本研究首次揭示了反映 DKD 逐步进展的胆汁酸代谢的特定变化，为 DKD 的早期识别和治疗策略提供了依据。
