Urinary Metabolomic Profiling Reveals Biological Pathways and Predictive Signatures Associated with Childhood Asthma.
Urinary Metabolomic Profiling Reveals Biological Pathways and Predictive Signatures Associated with Childhood Asthma.
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DOI：
10.2147/jaa.s281198
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发表时间：
2020
影响因子：
3.2
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Li S;Liu J;Zhou J;Wang Y;Jin F;Chen X;Yang J;Chen Z
由于哮喘的异质性，尽管付出了大量的努力，但其致病机制仍不完全清楚。然而，代谢组学可以提供生物系统的全局视图，使其成为进一步阐明哮喘机制和发现生物标志物的有价值的工具。应用GC-MS技术对哮喘儿童（n=30）和健康对照组（n=30）的尿代谢谱进行比较。对潜在结构的正交投影判别分析模型显示哮喘组和对照组有明显的分离（R2 x =0.137，R2 y =0.947，Q2=0.82）。共有20种差异代谢物被确定为判别因子，其中11种在哮喘组中显著增加，9种在对照组中显著减少。基于这些差异代谢产物的途径富集分析表明，鞘脂代谢、蛋白质生物合成和柠檬酸循环与哮喘密切相关。在鉴定的代谢物中，2-羟基丁酸显示出区分哮喘与健康对照的优异区分性能，AUC为0.969。我们的研究揭示了哮喘患者尿液代谢组的显著变化。一些干扰途径（如鞘脂代谢和柠檬酸循环）可能与哮喘的发病机制有关，2-羟基丁酸可能作为一个潜在的生物标志物诊断哮喘。
Despite considerable efforts, the pathogenic mechanisms of asthma are still incompletely understood, due to its heterogeneous nature. However, metabolomics can offer a global view of a biological system, making it a valuable tool for further elucidation of mechanisms and biomarker discovery in asthma. GC-MS–based metabolomic analysis was conducted for comparison of urine metabolic profiles between asthmatic children (n=30) and healthy controls (n=30). An orthogonal projections to latent structures discriminant–analysis model revealed a clear separation of the asthma and control groups (R2x=0.137, R2y=0.947, Q2=0.82). A total of 20 differential metabolites were identified as discriminant factors, of which eleven were significantly increased and nine decreased in the asthma group compared to the control group. Pathway-enrichment analysis based on these differential metabolites indicated that sphingolipid metabolism, protein biosynthesis, and citric acid cycle were strongly associated with asthma. Among the identified metabolites, 2-hydroxybutanoic acid showed excellent discriminatory performance for distinguishing asthma from healthy controls, with an AUC of 0.969. Our study revealed significant changes in the urine metabolome of asthma patients. Several perturbed pathways (eg, sphingolipid metabolism and citric acid cycle) may be related to asthma pathogenesis, and 2-hydroxybutanoic acid could serve as a potential biomarker for asthma diagnosis.