■脂质是结核分枝杆菌(Mtb)生长和繁殖的关键营养来源。尿液来源的细胞外囊泡(EV),因为它的非侵入性采样,脂质富集,和特定的排序字符,已被认为是结核病(TB)中生物标志物发现和发病机理阐明的有希望的研究目标。我们的目标是分析Mtb感染个体的脂质组,为尿液结核病检测的发展提供新的脂质特征,并为Mtb感染后的脂质代谢提供新的见解。
■来自41名参与者的尿液来源的细胞外囊泡(包括健康,肺结核,潜伏性结核病患者,和其他肺部疾病组)使用靶向脂质组学和蛋白质组学技术平台进行分离和单独检测。通过多变量和单变量统计分析筛选生物标志物,并用SPSS软件进行评价。使用RHmisc包装对脂质和蛋白质进行相关性分析。
■总的来说,我们确定了226脂质属于14类。其中,确定了7种潜在的结核病脂质生物标志物和6种潜伏性结核病感染(LTBI)。所有这些都被归类为二酰基甘油(DAG),单酰基甘油(MAG),游离脂肪酸(FFA),和胆固醇酯(CE)。其中,FFA(20:1)是诊断来自其他比较组的TB/LTBI的最有希望的生物标志物靶标,并且在区分TB与LTBI方面也具有良好的诊断性能,AUC为0.952。此外,增强的脂解作用早在个体潜伏性Mtb感染时就发生了,随着TB的进展,移植物脂质的比例逐渐升高。
■这项研究证明了Mtb感染患者的尿液EV的个体化脂质分布,揭示了用于TB/LTBI诊断的新型潜在脂质生物标志物,并探讨了EV脂质筏依赖性生物过程可能影响发病机理的机制。为结核病的后续诊断和治疗干预奠定了坚实的基础。
UNASSIGNED: Lipids are a key nutrient source for the growth and reproduction of Mycobacterium tuberculosis (Mtb). Urine-derived extracellular vesicles (EVs), because of its non-invasive sampling, lipid enrichment, and specific sorting character, have been recognized as a promising research target for biomarker discovery and pathogenesis elucidation in tuberculosis (TB). We aim to profile lipidome of Mtb-infected individuals, offer novel lipid signatures for the development of urine-based TB testing, and provide new insights into the lipid metabolism after Mtb infection.
UNASSIGNED: Urine-derived extracellular vesicles from 41 participants (including healthy, pulmonary tuberculosis, latent tuberculosis patients, and other lung disease groups) were isolated and individually detected using targeted lipidomics and proteomics technology platforms. Biomarkers were screened by multivariate and univariate statistical analysis and evaluated by SPSS software. Correlation analyses were performed on lipids and proteins using the R Hmisc package.
UNASSIGNED: Overall, we identified 226 lipids belonging to 14 classes. Of these, 7 potential lipid biomarkers for TB and 6 for latent TB infection (LTBI) were identified, all of which were classified into diacylglycerol (DAG), monoacylglycerol (MAG), free fatty acid (FFA), and cholesteryl ester (CE). Among them, FFA (20:1) was the most promising biomarker target in diagnosing TB/LTBI from other compared groups and also have great diagnostic performance in distinguishing TB from LTBI with AUC of 0.952. In addition, enhanced lipolysis happened as early as individuals got latent Mtb infection, and ratio of raft lipids was gradually elevated along TB progression.
UNASSIGNED: This study demonstrated individualized lipid profile of urinary EVs in patients with Mtb infection, revealed novel potential lipid biomarkers for TB/LTBI diagnosis, and explored mechanisms by which EV lipid raft-dependent bio-processes might affect pathogenesis. It lays a solid foundation for the subsequent diagnosis and therapeutic intervention of TB.