Metabolic characterization of tuberculous meningitis in a South African paediatric population using 1H NMR metabolomics

CSF Metabolomics of Tuberculous Meningitis: A Review

“…Disregarding CSF glucose and lactate, TBM was characterized by 18 statistically significant metabolites (Table 1): 7 of these metabolites (alanine, choline, isoleucine, myo-inositol, pyruvate, and valine) corresponded with the study by Zhang et al [29], and 10 metabolites (acetate, alanine, choline, citrate, creatinine, isoleucine, lysine, myo-inositol, pyruvate, and valine) overlapped with the previous study by Mason et al [22]. Eight unique CSF metabolites (2-hydroxybutyrate, carnitine, creatine, creatine phosphate, glutamate, glutamine, guanidinoacetate, and proline) associated with TBM were identified for the first time by van Zyl et al [28], and were linked to uncontrolled glucose metabolism, upregulated proline and creatine metabolism, detoxification, and the disrupted glutamate-glutamine cycle in TBM. Hence, these novel characteristic metabolites of TBM provided additional information towards our understanding of the condition.…”

“…Hence, these novel characteristic metabolites of TBM provided additional information towards our understanding of the condition. A hypothesis proffered by van Zyl et al [28] was that increased levels of 2-hydroxybutyrate in the CSF of TBM cases supports the concept of insulin resistance and uncontrolled glucose metabolism in M. tb-infected brains. Uncontrolled glucose metabolism results in an inability of glucose to enter the cells, and subsequently leads to reduced cellular glycolysis and ATP deprivation, ultimately, leading to the destabilization of the blood-brain barrier.…”

“…Using the online search criteria of "tuberculous meningitis" and "metabolomics" in PubMed, up to the end of 2020, yielded 14 hits; of these, 11 studies [19][20][21][22][23][24][25][26][27][28][29] contained metabolic information on TBM in CSF from humans, and are discussed in this review. Further examination of these 11 studies yielded three more CSF metabolomics studies on TBM [30][31][32].…”

“…In a follow-up of their 2015 NMR metabolomics study, Mason et al performed another metabolic characterization of a new South African TBM pediatric cohort (<12 years old) in 2020, again using untargeted NMR metabolomics [28]. From an original cache of 103 suspected TBM cases and 97 controls, a strict filtering of the samples was applied, and only 23 definite TBM cases and 33 controls were analyzed.…”

“…From an original cache of 103 suspected TBM cases and 97 controls, a strict filtering of the samples was applied, and only 23 definite TBM cases and 33 controls were analyzed. The strength of this study by van Zyl et al [28] was that stringent quality assurance steps were applied. Using 24 quality control (QC) samples, all NMR spectral regions that were consistently unreliable (coefficient of variance greater than 50%) were removed from analysis.…”