目前,全世界有数百万人患有慢性肾病(CKD)。在终末期需要肾脏替代疗法。从组学角度更好地理解CKD病理生理学的努力已经揭示了几种样品来源中的主要分子参与者。专注于非侵入性来源,CKD中的肠道微生物群落似乎受到干扰,而许多人尿肽也失调。然而,研究通常集中在孤立的组学技术上,因此可能缺少多学科方法可以提供的补充病理生理信息.为此,分析了人尿肽组,并将其与从110名非CKD或CKD个体收集的临床和粪便微生物组(16S测序)数据进行整合(早期,中等,或晚期CKD阶段)未接受透析。使用临床和分子数据的不同组合在三维空间中对参与者进行可视化。在减少的数据空间中区分患者组的最有影响力的临床变量是,其中,血清尿素,血红蛋白,总血液蛋白,尿白蛋白,尿红细胞,血压,胆固醇测量,身体质量指数,布里斯托尔大便得分,和吸烟;相关变量也是微生物类群,包括罗斯布里亚,Butyricicocus,Flavonifractor,Burkholderiales,Holdemania,增效草科,肠纹肌,和Senegalimassilia;尿肽组片段主要来自胶原蛋白来源的蛋白质;非胶原蛋白亲本蛋白中有FXYD2,MGP,FGA,APOA1和CD99。尿肽组似乎捕获了CKD背景下的实质性变化。与单独的临床数据相比,整合临床和分子数据有助于改善队列分离,指示,再一次,这些综合信息在临床实践中的附加价值。
Millions of people worldwide currently suffer from chronic kidney disease (CKD), requiring kidney replacement therapy at the end stage. Endeavors to better understand CKD pathophysiology from an omics perspective have revealed major molecular players in several sample sources. Focusing on non-invasive sources, gut microbial communities appear to be disturbed in CKD, while numerous human urinary peptides are also dysregulated. Nevertheless, studies often focus on isolated omics techniques, thus potentially missing the complementary pathophysiological information that multidisciplinary approaches could provide. To this end, human urinary
peptidome was analyzed and integrated with clinical and fecal microbiome (16S sequencing) data collected from 110 Non-CKD or CKD individuals (Early, Moderate, or Advanced CKD stage) that were not undergoing dialysis. Participants were visualized in a three-dimensional space using different combinations of clinical and molecular data. The most impactful clinical variables to discriminate patient groups in the reduced dataspace were, among others, serum urea, haemoglobin, total blood protein, urinary albumin, urinary erythrocytes, blood pressure, cholesterol measures, body mass index, Bristol stool score, and smoking; relevant variables were also microbial taxa, including Roseburia, Butyricicoccus, Flavonifractor, Burkholderiales, Holdemania, Synergistaceae, Enterorhabdus, and Senegalimassilia; urinary
peptidome fragments were predominantly derived from proteins of collagen origin; among the non-collagen parental proteins were FXYD2, MGP, FGA, APOA1, and CD99. The urinary
peptidome appeared to capture substantial variation in the CKD context. Integrating clinical and molecular data contributed to an improved cohort separation compared to clinical data alone, indicating, once again, the added value of this combined information in clinical practice.