Metabolic characterization of tuberculous meningitis in a South African paediatric population using 1H NMR metabolomics. Issue 5 (November 2020)

• Record Type: Journal Article
• Authors: van Zyl, Christiaan De Wet; Loots, Du Toit; Solomons, Regan; van Reenen, Mari; Mason, Shayne
• Is Part Of: Journal of infection. Volume 81:Issue 5(2020)
• Page Start: 743
• Page End: 752
• Publication Date: 2020-11
• Subjects: Cerebrospinal fluid (CSF) -- Proton magnetic resonance (1H NMR) spectroscopy -- Tuberculous meningitis (TBM) -- Paediatrics -- Metabolomics -- Metabolic characterization; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2020.06.078
• Languages: English
• ISSNs: 0163-4453

Abstract

Highlights: Eight novel metabolites characterizing definite TBM. 2-Hydroxybutyrate, identified for the first time in CSF of TBM cases, linked to uncontrolled glucose metabolism. TBM exhibit upregulated creatine metabolism, disrupted glutamate-glutamine cycle, elevated neuroprotective free carnitine. Elevated proline linked to classic TBM-hallmark of elevated protein. Collectively, our findings imply destabilization and increased permeability of the bloodbrain barrier in TBM. Summary: Objective: To better characterize the cerebrospinal fluid (CSF) metabolic profile of tuberculous meningitis (TBM) cases using a South African paediatric cohort. Methods: 1 H 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.