Department of Pathogen Biology, College of Basic Medical Sciences, Jilin University, Changchun, China.
School of Pharmaceutical Sciences, Jilin University, Changchun, China.
Biomed Res Int. 2018 Sep 23;2018:2860521. doi: 10.1155/2018/2860521. eCollection 2018.
Asthma as a chronic heterogeneous disease seriously affects the quality of life. Incorrect identification for its clinical phenotypes lead to a huge waste of medical resources. Metabolomic technique as a novel approach to explore the pathogenesis of diseases have not been used to study asthma based on their clear defined inflammatory phenotypes. This study is aimed to distinguish the divergent metabolic profile in different asthma phenotypes and clarify the pathogenesis of them.
Participants including eosinophilic asthmatics (EA, n=13), noneosinophilic asthmatics (NEA, n=16), and healthy controls (HC, n=15) were enrolled. A global profile of untargeted serum metabolomics was identified with Ultra Performance Liquid Chromatography-Mass Spectrometry technique.
Multivariate analysis was performed and showed a clear distinction between EA, NEA, and HC. A total of 18 different metabolites were recognized between the three groups based on OPLS-DA model and involved in 10 perturbed metabolic pathways. Glycerophospholipid metabolism, retinol metabolism, and sphingolipid metabolism were identified as the most significant changed three pathways (impact > 0.1 and -log() > 4) between the phenotypes.
We showed that the different inflammatory phenotypes of asthma involve the immune regulation, energy, and nutrients metabolism. The clarified metabolic profile contributes to understanding the pathophysiology of asthma phenotypes and optimizing the therapeutic strategy against asthma heterogeneity.
哮喘是一种慢性异质性疾病,严重影响生活质量。由于对其临床表型的识别不正确,导致医疗资源的巨大浪费。代谢组学技术作为一种探索疾病发病机制的新方法,尚未用于基于明确炎症表型的哮喘研究。本研究旨在区分不同哮喘表型的发散代谢谱,并阐明其发病机制。
纳入嗜酸性粒细胞性哮喘(EA,n=13)、非嗜酸性粒细胞性哮喘(NEA,n=16)和健康对照(HC,n=15)三组参与者。采用超高效液相色谱-质谱联用技术对非靶向血清代谢组学进行了全面分析。
对多变量分析表明,EA、NEA 和 HC 之间有明显的区别。基于 OPLS-DA 模型,三组之间共鉴定出 18 种不同的代谢物,涉及 10 个失调的代谢途径。甘油磷脂代谢、视黄醇代谢和鞘脂代谢被确定为表型之间变化最大的三个途径(影响>0.1 和-log() > 4)。
我们表明哮喘的不同炎症表型涉及免疫调节、能量和营养代谢。阐明的代谢谱有助于了解哮喘表型的病理生理学,并优化针对哮喘异质性的治疗策略。