Metabolomic profiling reveals the step-wise alteration of bile acid metabolism in patients with diabetic kidney disease.

IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Nutrition & Diabetes Pub Date : 2024-10-09 DOI:10.1038/s41387-024-00315-0
Qing Zhang, Liqian Lu, Jiao Wang, Manman Lu, Dongwei Liu, Chunyu Zhou, Zhangsuo Liu
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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代谢组学分析揭示了糖尿病肾病患者胆汁酸代谢的逐步改变。
背景:糖尿病肾病(DKD)是糖尿病的主要并发症,同时伴有肠道菌群失调和糖代谢紊乱,这与胆汁酸(BA)代谢密切相关。然而,有关胆汁酸代谢参与 DKD 发病机制的研究还很有限。本研究旨在探索DKD中胆汁酸的代谢组谱,并分析其与DKD进展的关系:方法:建立了一种超高效液相色谱串联质谱(UPLC-MS/MS)方法,定量检测DKD或T2DM患者和健康人(每组30人)血浆、粪便和尿液样本中的BAs。通过正交偏最小二乘判别分析(OPLS-DA)和接收效应特征曲线(ROC)确定了与 DKD 相关的关键 BAs。通过多项式回归和皮尔逊相关分析,评估了关键BA与反映DKD进展的临床指标之间的相关性:结果:50种生物碱的代谢组学分析表明,DKD患者血浆和粪便中的生物碱呈明显的阶梯状变化,而尿液中的生物碱则很少。血浆中的 8 种 BAs、粪便中的 8 种 BAs 和尿液中的 3 种 BAs 表达异常,同时血浆中胆酸、脱氧胆酸、辰去氧胆酸、熊去氧胆酸和土胆酸的共轭/非共轭比值升高,粪便中胆酸、辰去氧胆酸和石胆酸的共轭/非共轭比值升高。此外,血浆中甘油脱氧胆酸水平的升高以及粪便中甘油石胆酸、7-酮脱氧胆酸和辰脱氧胆酸-3-β-D-葡萄糖醛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:我们的研究首次揭示了反映 DKD 逐步进展的 BA 代谢特异性改变,为 DKD 的早期识别和治疗策略提供了依据。
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来源期刊
Nutrition & Diabetes
Nutrition & Diabetes ENDOCRINOLOGY & METABOLISM-NUTRITION & DIETETICS
CiteScore
9.20
自引率
0.00%
发文量
50
审稿时长
>12 weeks
期刊介绍: Nutrition & Diabetes is a peer-reviewed, online, open access journal bringing to the fore outstanding research in the areas of nutrition and chronic disease, including diabetes, from the molecular to the population level.
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