PDF(Pubmed)
Abstract：
Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12 years). Little is known of the associated metabolic changes. This study aimed to identify characteristic metabolic markers that differentiate severe cases of paediatric TBM from controls, through non-invasive urine collection. Urine samples selected for this study were from two paediatric groups. Group 1: controls (n = 44): children without meningitis, no neurological symptoms and from the same geographical region as group 2. Group 2: TBM cases (n = 13): collected from paediatric patients that were admitted to Tygerberg Hospital in South Africa on the suspicion of TBM, mostly severely ill; with a later confirmation of TBM. Untargeted 1H NMR-based metabolomics data of urine were generated, followed by statistical analyses via MetaboAnalyst (v5.0), and the identification of important metabolites. Twenty nine urinary metabolites were identified as characteristic of advanced TBM and categorized in terms of six dysregulated metabolic pathways: 1) upregulated tryptophan catabolism linked to an altered vitamin B metabolism; 2) perturbation of amino acid metabolism; 3) increased energy production-metabolic burst; 4) disrupted gut microbiota metabolism; 5) ketoacidosis; 6) increased nitrogen excretion. We also provide original biological insights into this biosignature of urinary metabolites that can be used to characterize paediatric TBM patients in a South African cohort.
摘要：
结核性脑膜炎（TBM）是一种严重的结核病，具有高神经发病率和死亡率，尤其是在儿科人群中（年龄≤12岁）。对相关的代谢变化知之甚少。这项研究旨在确定特征代谢标志物，以区分儿科TBM与对照组的严重病例。通过非侵入性尿液收集。本研究选择的尿液样本来自两个儿科组。第1组：对照组（n=44）：无脑膜炎儿童，没有神经系统症状，并且来自与第2组相同的地理区域。第2组：TBM病例（n=13）：从怀疑TBM的南非Tygerberg医院收治的儿科患者中收集，大多是重病；后来确认了TBM。产生了基于非靶向1HNMR的尿液代谢组学数据，随后通过MetaboAnalyst(v5.0)进行统计分析，以及重要代谢物的鉴定。29种尿代谢物被鉴定为晚期TBM的特征，并根据六种代谢途径失调进行分类：1）与维生素B代谢改变有关的色氨酸分解代谢上调；2）氨基酸代谢紊乱；3）能量产生-代谢爆发增加；4）肠道微生物群代谢中断；5）酮症酸中毒；6）氮排泄增加。我们还提供了对尿代谢物的这种生物特征的原始生物学见解，可用于表征南非队列中的儿科TBM患者。
