Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid.
The defining feature of the cerebrospinal fluid (CSF) collected from infants and children with tuberculous meningitis (TBM), derived from an earlier untargeted nuclear magnetic resonance (NMR) metabolomics study, was highly elevated lactic acid. Undetermined was the contribution from host response (L-lactic acid) or of microbial origin (D-lactic acid), which was set out to be determined in this study.



In this follow-up study, we used targeted ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) to determine the ratio of the L and D enantiomers of lactic acid in these CSF samples.



Here we report for the first time that the lactic acid observed in the CSF of confirmed TBM cases was in the L-form and solely a response from the host to the infection, with no contribution from any bacteria. The significance of elevated lactic acid in TBM appears to be that it is a crucial energy substrate, used preferentially over glucose by microglia, and exhibits neuroprotective capabilities.



These results provide experimental evidence to support our conceptual astrocyte-microglia lactate shuttle model formulated from our previous NMR-based metabolomics study - highlighting the fact that lactic acid plays an important role in neuroinflammatory diseases such as TBM. Furthermore, this study reinforces our belief that the determination of enantiomers of metabolites corresponding to infectious diseases is of critical importance in substantiating the clinical significance of disease markers.
Centre for Human Metabolomics, Faculty of Natural Sciences, North-West University (Potchefstroom Campus), Private Bag X6001, Potchefstroom, 2531, South Africa. nmr.nwu@gmail.com.
Shayne
S
Mason
Centre for Human Metabolomics, Faculty of Natural Sciences, North-West University (Potchefstroom Campus), Private Bag X6001, Potchefstroom, 2531, South Africa.
Carolus J
CJ
Reinecke
Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Willem
W
Kulik
Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Arno
A
van Cruchten
Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, 7505, South Africa.
Regan
R
Solomons
Department of Paediatric Infectious Diseases-Immunology and Rheumatology, Vrije Universiteit Medical Centre, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
A Marceline Tutu
AM
van Furth
D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007536:Isomerism; D019344:Lactic Acid / Q000134:cerebrospinal fluid*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D053719:Tandem Mass Spectrometry; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D019344:Lactic Acid
Cerebrospinal fluid (CSF); Enantiomers; L- and D-lactic acid; Tuberculous meningitis (TBM); Ultra-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC–ESI–MS/MS)