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结核性脑膜炎患儿尿液中烷烃及其他挥发性有机化合物的探索性研究。

Exploratory investigation of urinary alkanes and other volatile organic compounds in paediatric patients with tuberculous meningitis.

作者信息

Isaiah Simon, Loots Du Toit, van Furth A Marceline Tutu, Solomons Regan, van Elsland Sabine, van der Kuip Martijn, Mason Shayne

机构信息

Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa.

Pediatric Infectious Diseases and Immunology, Amsterdam University Medical Centers, Emma Children's Hospital, Vrije Universiteit, De Boelelaan 1117, Amsterdam, The Netherlands.

出版信息

Metabolomics. 2025 Aug 11;21(5):107. doi: 10.1007/s11306-025-02304-5.

DOI:10.1007/s11306-025-02304-5
PMID:40789978
Abstract

BACKGROUND

Tuberculous meningitis (TBM) is a disease caused by Mycobacterium tuberculosis (M. tb) infection of the brain. Alkanes and other volatile organic compounds (VOCs) are biologically important metabolites that are used by infectious mycobacteria species for growth and survival strategies.

OBJECTIVE

This study investigated the altered alkanes and other VOCs in the urine from paediatric cases with TBM.

METHOD

We used untargeted gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS) to analyse and compare all volatile, underivatised compounds present in the urine from 27 confirmed cases of paediatric TBM over a treatment period of six months, as well as a control group (n = 13).

RESULT

Four elevated alkanes (pentadecane, 5,7-dimethyl-undecane, 4,7-dimethyl-undecane, and 2,6-dimethyl-undecane), three alkenes (decreased 2,5-dimethyl-2-hexene and 4,4-dimethyl-1-pentene, and increased 3-methoxy-1-pentene), and three other VOCs of biological interest (decreased 2-butenoic acid methyl ester and 3-heptanone, and increased 2-pyrrolidinone) were identified as statistically significant. These volatile compounds remained perturbed during the TBM treatment.

CONCLUSION

This study discovered new systemic metabolic information about M. tb in the host and the role of alkanes and VOCs in the potential persistence of M. tb. We demonstrate the value of targeting alkanes and other VOCs for future metabolomics studies of M. tb.

摘要

背景

结核性脑膜炎(TBM)是由结核分枝杆菌(M. tb)感染大脑引起的疾病。烷烃和其他挥发性有机化合物(VOCs)是具有重要生物学意义的代谢产物,感染性分枝杆菌利用它们来实现生长和生存策略。

目的

本研究调查了小儿结核性脑膜炎患者尿液中烷烃和其他挥发性有机化合物的变化。

方法

我们使用非靶向气相色谱-飞行时间质谱联用仪(GC-TOFMS)分析并比较了27例确诊的小儿结核性脑膜炎患者在六个月治疗期间尿液中所有挥发性、未衍生化的化合物,以及一个对照组(n = 13)。

结果

确定了四种升高的烷烃(十五烷、5,7-二甲基-十一烷、4,7-二甲基-十一烷和2,6-二甲基-十一烷)、三种烯烃(2,5-二甲基-2-己烯和4,4-二甲基-1-戊烯减少,3-甲氧基-1-戊烯增加)以及其他三种具有生物学意义的挥发性有机化合物(2-丁烯酸甲酯和3-庚酮减少,2-吡咯烷酮增加)具有统计学意义。这些挥发性化合物在结核性脑膜炎治疗期间仍处于紊乱状态。

结论

本研究发现了宿主中结核分枝杆菌新的全身代谢信息以及烷烃和挥发性有机化合物在结核分枝杆菌潜在持续存在中的作用。我们证明了针对烷烃和其他挥发性有机化合物进行未来结核分枝杆菌代谢组学研究的价值。

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