布鲁氏菌病患者血清差异代谢组学分析

Differential metabolomics analysis of serum in brucellosis patients

目的研究健康人群、布鲁氏菌病患者与治疗组的血清代谢组分,筛选突出的差异性代谢物,探讨潜在生物标志物的应用信息及参与的生物途径。方法通过液相色谱-质谱联用(LC-MS)非靶向代谢组学技术检测代谢物,结合主成分分析方法(PCA)、最小偏二乘判别分析(PLS-DA)、正交最小偏二乘判别分析(OPLS-DA)、200次置换检验等多元统计方法筛选差异生物标记物,并利用KEGG数据库对筛选的差异代谢物进行注释和通路富集。结果在正常人群和患病组比较中,共鉴定到128个差异代谢物,其中44个上调,84个下调;在患病组和治疗组比较中,共鉴定到180个差异代谢物,其中,41个上调,139个下调。这些差异代谢物主要集中在缬氨酸、亮氨酸和异亮氨酸生物合成、D氨基酸代谢、咖啡因代谢、赖氨酸降解等途径。布鲁氏菌病患者经三联抗菌药物治疗后,显示回调的有谷氨酸、棕榈酸、次黄嘌呤、十五烷酸、烟酰胺等18个关键差异代谢物,考虑可作为诊断及治疗布鲁氏菌病的潜在生物标志物。结论通过非靶向代谢组学分析布鲁氏菌病患者血清中的差异代谢物,为布鲁氏菌病的临床诊断、治疗及预后提供参考。

OBJECTIVE To study the serum metabolic components of healthy populations,brucellosis patients and treatment groups,to screen the prominent differential metabolites,and to explore the application of potential biomarkers and the biological pathways involved.METHODS LC-MS non-targeted metabolomics technology was used to detect metabolites,and multivariate statistical methods such as principal component analysis(PCA),least partial square discriminant analysis(PLS-DA),orthogonal least partial square discriminant analysis(OPLS-DA),and 200 displacement tests were used to screen differential biomarkers.KEGG database was used for annotation and pathway enrichment of the screened differential metabolites.RESULTS A total of 128 different metabolites were identified in the comparison of the normal and the diseased groups,of which 44 were up-regulated and 84 were down-regulated.A total of 180 different metabolites were identified in the comparison of the disease and the treatment groups,of which 41 were up-regulated and 139 were down-regulated.These differential metabolites mainly focused on the pathway of valine,leucine and isoleucine biosynthesis,Damino acid metabolism,caffeine metabolism,lysine degradation and so on.Eighteen key differential metabolites,including glutamate acid,hexadecanoic acid,hypoxanthine,pentadecanoic acid and nicotinamide were showed to regress after triple antimicrobial drug therapy in brucellosis patients,and were considered as potential biomarkers for the diagnosis and treatment of brucellosis.CONCLUSION Differential metabolites in the serum of brucellosis patients were analyzed by nontargeted metabolomics,which provided a reference for the clinical diagnosis,treatment and prognosis of brucellosis.