Samuel Victory, Solomons Regan, Mason Shayne
Biochemistry Department, Focus Area for Human Metabolomics, North-West University, Potchefstroom, South Africa.
Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
PLoS One. 2024 Dec 17;19(12):e0314854. doi: 10.1371/journal.pone.0314854. eCollection 2024.
To investigate metabolic markers linked to Mycobacterium tuberculosis (M. tb) in the cerebrospinal fluid (CSF) of a South African cohort of paediatric tuberculous meningitis (TBM).
Targeted proton magnetic resonance (1H-NMR) spectroscopy and two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) metabolomics approaches were used to evaluate M. tb-linked metabolites in the CSF of 21 definite cases of TBM and 25 control cases. Uni- and multivariate statistical analyses were performed.
Four statistically significant metabolites were identified to discriminate TBM cases from controls. Mannose and arabinose were found at lower concentrations in the TBM group. Nonanoic acid and propanoic acid were found in higher concentrations in the definite TBM group.
We identified the novel presence of nonanoic acid for the first time as a M. tb-linked marker in the CSF of cases of TBM, possibly as a degradation product of the M. tb cell wall. Propanoic acid can be related to perturbed brain neuro-energetics and neuro-inflammation in TBM cases and is likely a host-response metabolite. Mannose and arabinose-supposed surrogates for lipoarabinomannan, a component of the M. tb cell wall-were not reliable markers for M. tb. Further research should focus on the analysis of fatty acids in the CSF of patients with TBM.
在南非一组儿童结核性脑膜炎（TBM）患者的脑脊液（CSF）中，研究与结核分枝杆菌（M. tb）相关的代谢标志物。
采用靶向质子磁共振（1H-NMR）光谱法和二维气相色谱-飞行时间质谱联用（GCxGC-TOFMS）代谢组学方法，评估21例确诊TBM患者和25例对照患者脑脊液中与M. tb相关的代谢物。进行了单变量和多变量统计分析。
确定了四种具有统计学意义的代谢物，可区分TBM病例与对照。在TBM组中发现甘露糖和阿拉伯糖浓度较低。在确诊的TBM组中发现壬酸和丙酸浓度较高。
我们首次确定壬酸作为TBM病例脑脊液中与M. tb相关的标志物新出现，可能是M. tb细胞壁的降解产物。丙酸可能与TBM病例中大脑神经能量和神经炎症紊乱有关，可能是一种宿主反应代谢物。甘露糖和阿拉伯糖——假定为脂阿拉伯甘露聚糖（M. tb细胞壁的一种成分）的替代物——不是M. tb的可靠标志物。进一步的研究应集中于分析TBM患者脑脊液中的脂肪酸。
