Metabolic characterization of tuberculous meningitis in a South African paediatric population using 1H NMR metabolomics.
OBJECTIVE
To better characterize the cerebrospinal fluid (CSF) metabolic profile of tuberculous meningitis (TBM) cases using a South African paediatric cohort.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['van Zyl|Christiaan De Wet|CW|', 'Loots|Du Toit|DT|', 'Solomons|Regan|R|', 'van Reenen|Mari|M|', 'Mason|Shayne|S|']
D002648:Child D015331:Cohort Studies D006801:Humans D055432:Metabolomics D066244:Proton Magnetic Resonance Spectroscopy D014390:Tuberculosis, Meningeal
Metabolic characterization Paediatrics Metabolomics Cerebrospinal fluid (CSF) Tuberculous meningitis (TBM) Proton magnetic resonance ((1)H NMR) spectroscopy