PDF(Sci-hub)
Abstract：
To better characterize the cerebrospinal fluid (CSF) metabolic profile of tuberculous meningitis (TBM) cases using a South African paediatric cohort.
1H NMR metabolomics was used to analyse the CSF of a South African paediatric cohort. Univariate and multivariate statistical analyses were performed to compare a homogeneous control group with a well-defined TBM group.
Twenty metabolites were identified to discriminate TBM cases from controls. As expected, reduced glucose and elevated lactate were the dominating discriminators. A closer investigation of the CSF metabolic profile yielded 18 metabolites of statistical significance. Ten metabolites (acetate, alanine, choline, citrate, creatinine, isoleucine, lysine, myo-inositol, pyruvate and valine) overlapped with two other prior investigations. Eight metabolites (2-hydroxybutyrate, carnitine, creatine, creatine phosphate, glutamate, glutamine, guanidinoacetate and proline) were unique to our paediatric TBM cohort.
Through strict exclusion criteria, quality control checks and data filtering, eight unique CSF metabolites associated with TBM were identified for the first time and linked to: uncontrolled glucose metabolism, upregulated proline and creatine metabolism, detoxification and disrupted glutamate-glutamine cycle in the TBM samples. Associated with oxidative stress and chronic neuroinflammation, our findings collectively imply destabilization, and hence increased permeability, of the blood-brain barrier in the TBM cases.
1H NMR metabolomics was used to analyse the CSF of a South African paediatric cohort. Univariate and multivariate statistical analyses were performed to compare a homogeneous control group with a well-defined TBM group.
Twenty metabolites were identified to discriminate TBM cases from controls. As expected, reduced glucose and elevated lactate were the dominating discriminators. A closer investigation of the CSF metabolic profile yielded 18 metabolites of statistical significance. Ten metabolites (acetate, alanine, choline, citrate, creatinine, isoleucine, lysine, myo-inositol, pyruvate and valine) overlapped with two other prior investigations. Eight metabolites (2-hydroxybutyrate, carnitine, creatine, creatine phosphate, glutamate, glutamine, guanidinoacetate and proline) were unique to our paediatric TBM cohort.
Through strict exclusion criteria, quality control checks and data filtering, eight unique CSF metabolites associated with TBM were identified for the first time and linked to: uncontrolled glucose metabolism, upregulated proline and creatine metabolism, detoxification and disrupted glutamate-glutamine cycle in the TBM samples. Associated with oxidative stress and chronic neuroinflammation, our findings collectively imply destabilization, and hence increased permeability, of the blood-brain barrier in the TBM cases.
摘要：
使用南非儿科队列更好地表征结核性脑膜炎（TBM）病例的脑脊液（CSF）代谢谱。
1HNMR代谢组学用于分析南非儿科队列的CSF。进行了单变量和多变量统计分析，以比较均质对照组与明确定义的TBM组。
确定了20种代谢物以将TBM病例与对照区分开。不出所料,降低的葡萄糖和升高的乳酸是主要的鉴别器。对CSF代谢谱的更仔细的研究得出了18种具有统计学意义的代谢物。十种代谢物（乙酸，丙氨酸,胆碱，柠檬酸盐肌酐,异亮氨酸,赖氨酸，肌醇,丙酮酸和缬氨酸）与其他两项先前研究重叠。八种代谢物（2-羟基丁酸，肉碱,肌酸,磷酸肌酸,谷氨酸,谷氨酰胺,胍基乙酸盐和脯氨酸）是我们儿科TBM队列所独有的。
通过严格的排除标准，质量控制检查和数据过滤，首次发现了与TBM相关的八种独特的CSF代谢物，并与：不受控制的葡萄糖代谢，上调脯氨酸和肌酸代谢，解毒和破坏TBM样品中的谷氨酸-谷氨酰胺循环。与氧化应激和慢性神经炎症相关，我们的发现共同暗示了不稳定，因此增加了渗透性，TBM病例中的血脑屏障。
1HNMR代谢组学用于分析南非儿科队列的CSF。进行了单变量和多变量统计分析，以比较均质对照组与明确定义的TBM组。
确定了20种代谢物以将TBM病例与对照区分开。不出所料,降低的葡萄糖和升高的乳酸是主要的鉴别器。对CSF代谢谱的更仔细的研究得出了18种具有统计学意义的代谢物。十种代谢物（乙酸，丙氨酸,胆碱，柠檬酸盐肌酐,异亮氨酸,赖氨酸，肌醇,丙酮酸和缬氨酸）与其他两项先前研究重叠。八种代谢物（2-羟基丁酸，肉碱,肌酸,磷酸肌酸,谷氨酸,谷氨酰胺,胍基乙酸盐和脯氨酸）是我们儿科TBM队列所独有的。
通过严格的排除标准，质量控制检查和数据过滤，首次发现了与TBM相关的八种独特的CSF代谢物，并与：不受控制的葡萄糖代谢，上调脯氨酸和肌酸代谢，解毒和破坏TBM样品中的谷氨酸-谷氨酰胺循环。与氧化应激和慢性神经炎症相关，我们的发现共同暗示了不稳定，因此增加了渗透性，TBM病例中的血脑屏障。
