{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:19:37Z","timestamp":1787026777673,"version":"build-2736575974"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged \u226412\u00a0years). 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\u2013metabolic 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.<\/jats:p>","DOI":"10.3389\/fmolb.2024.1253983","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:41:13Z","timestamp":1710463273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population"],"prefix":"10.3389","volume":"11","author":[{"given":"Simon","family":"Isaiah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du Toit","family":"Loots","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"van Reenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan","family":"Solomons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"van Elsland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Marceline","family":"Tutu van Furth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"van der Kuip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayne","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2922","DOI":"10.1038\/s41598-021-82445-4","article-title":"Urine lipoarabinomannan in HIV uninfected, smear negative, symptomatic TB patients: effective sample pretreatment for a sensitive immunoassay and mass spectrometry","volume":"11","author":"Amin","year":"2021","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"857","DOI":"10.3390\/microorganisms9040857","article-title":"Defeating paediatric tuberculous meningitis: applying the WHO \u201cdefeating meningitis by 2030: global roadmap\u201d","volume":"9","author":"Basu Roy","year":"2021","journal-title":"Microorganisms"},{"key":"B3","doi-asserted-by":"publisher","first-page":"185","DOI":"10.5505\/ejm.2023.49404","article-title":"Investigation of the predictive value of amino acids for tuberculous meningitis, aseptic meningitis and bacterial meningitis","volume":"28","author":"Binici","year":"2023","journal-title":"East. J. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"20130427","DOI":"10.1098\/rstb.2013.0427","article-title":"The application of transcriptional blood signatures to enhance our understanding of the host response to infection: the example of tuberculosis","volume":"369","author":"Blankley","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond., B, Biol. Sci."},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-40337-8","volume-title":"Physician's guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases","author":"Blau","year":"2014"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e73076","DOI":"10.1371\/journal.pone.0073076","article-title":"The human urine metabolome","volume":"8","author":"Bouatra","year":"2013","journal-title":"PloS one"},{"key":"B7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fnins.2014.00012","article-title":"Kynurenines in CNS disease: regulation by inflammatory cytokines","volume":"8","author":"Campbell","year":"2014","journal-title":"Front. Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1017\/s0033291700013817","article-title":"N-methylnicotinamide excretion and affective disorders","volume":"6","author":"Cazzullo","year":"1976","journal-title":"Psychol. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1093\/clinchem\/25.10.1791","article-title":"Measurement of 4-hydroxyphenylacetic aciduria as a screening test for small-bowel disease","volume":"25","author":"Chalmers","year":"1979","journal-title":"J. Clin. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1007\/BF00970739","article-title":"L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor","volume":"20","author":"Chang","year":"1995","journal-title":"Neurochem. Res."},{"key":"B11","first-page":"236","volume-title":"Organic acid profiling","author":"Chapman","year":"2020"},{"key":"B12","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1007\/s11306-016-1073-y","article-title":"Comprehensive 1 H NMR metabolic profiling of body fluids for differentiation of meningitis in adults","volume":"12","author":"Chatterji","year":"2016","journal-title":"Metabolomics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1136\/jnnp.44.9.791","article-title":"Cerebrospinal fluid amino acid concentrations in patients with viral and tuberculous meningitis","volume":"44","author":"Corston","year":"1981","journal-title":"J. Neurology, Neurosurg. Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.3390\/nu10111564","article-title":"Glutamine: metabolism and immune function, supplementation and clinical translation","volume":"10","author":"Cruzat","year":"2018","journal-title":"Nutrients"},{"key":"B15","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.arcped.2018.02.005","article-title":"Parenteral nutrition for preterm infants: issues and strategy","volume":"25","author":"Darmaun","year":"2018","journal-title":"Arch. Pediatr."},{"key":"B16","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/JLB.MR0318-102R","article-title":"The pathogenesis of tuberculous meningitis","volume":"105","author":"Davis","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"B17","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-802896-4.00003-1","article-title":"Chapter 2 - amino acids disorders","volume-title":"Biomarkers in inborn errors of metabolism","author":"Dearmond","year":"2017"},{"key":"B18","doi-asserted-by":"publisher","first-page":"S77","DOI":"10.1046\/j.1523-1755.2001.59780077.x","article-title":"Endogenous guanidino compounds as uremic neurotoxins","volume":"59","author":"De Deyn","year":"2001","journal-title":"Kidney Int."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0144088","DOI":"10.1371\/journal.pone.0144088","article-title":"Estimation of D-arabinose by gas chromatography\/mass spectrometry as surrogate for mycobacterial lipoarabinomannan in human urine","volume":"10","author":"De","year":"2015","journal-title":"PLoS One"},{"key":"B107","article-title":"Biochemistry, ketogenesis","volume-title":"Statpearls","author":"Dhillon","year":"2021"},{"key":"B20","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1093\/tropej\/42.5.256","article-title":"Pediatric meningitis in the Western cape province of South Africa","volume":"42","author":"Donald","year":"1996","journal-title":"J. Trop. Pediatr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1097\/QCO.0000000000000648","article-title":"Tuberculous meningitis: where to from here?","volume":"33","author":"Donovan","year":"2020","journal-title":"Curr. Opin. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1007\/s11306-019-1620-4","article-title":"A laboratory approach for characterizing chronic fatigue: what does metabolomics tell us?","volume":"15","author":"Erasmus","year":"2019","journal-title":"Metabolomics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/s0009-9120(77)92494-8","article-title":"Pitfalls in metabolic studies: the origin of urinary p-tyramine","volume":"10","author":"Fellaman","year":"1977","journal-title":"Clin. Biochem."},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1016\/B0-12-227055-X\/00040-7","article-title":"AMINO ACIDS, metabolism","volume-title":"Encyclopedia of food sciences and nutrition","author":"Ferreira","year":"2003"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e69896","DOI":"10.1371\/journal.pone.0069896","article-title":"Soluble markers of the Toll-like receptor 4 pathway differentiate between active and latent tuberculosis and are associated with treatment responses","volume":"8","author":"Feruglio","year":"2013","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1078\/0940-2993-00214","article-title":"Possible role of 1-methylnicotinamide in the pathogenesis of Parkinson's disease","volume":"53","author":"Fukushima","year":"2002","journal-title":"Exp. Toxicol. Pathol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e0257214","DOI":"10.1371\/journal.pone.0257214","article-title":"Increased levels of circulating LPS during Tuberculosis prevails in patients with advanced pulmonary involvement","volume":"16","author":"Gallucci","year":"2021","journal-title":"PLoS One"},{"key":"B28","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1093\/ajcp\/55.3.318","article-title":"Para-hydroxyphenylacetic and homovanillic acid excretion: variation during growth and in cystic fibrosis and other pulmonary diseases","volume":"55","author":"Garrettson","year":"1971","journal-title":"Am. J. Clin. Pathol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11306-010-0201-3","article-title":"An overflow of\u2026 what else but metabolism!","volume":"6","author":"Goodacre","year":"2010","journal-title":"Metabolomics"},{"key":"B30","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3390\/metabo12030272","article-title":"Fast and sensitive quantification of AccQ-Tag derivatized amino acids and biogenic amines by UHPLC-UV analysis from complex biological samples","volume":"12","author":"Guba","year":"2022","journal-title":"Metabolites"},{"key":"B31","doi-asserted-by":"publisher","first-page":"3007","DOI":"10.1182\/blood.V92.9.3007","article-title":"Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing","volume":"92","author":"Hampton","year":"1998","journal-title":"Blood, Am. J. Hematol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fmolb.2019.00022","article-title":"Editorial: aromatic amino acid metabolism","volume":"6","author":"Han","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"B33","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-92678-0","volume-title":"Meningitis and encephalitis","author":"Hasbun","year":"2018"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1016\/s0021-9258(18)48650-4","article-title":"The biosynthesis of free and phosphatide myo-inositol from glucose by mammalian tissue slices","volume":"238","author":"Hauser","year":"1963","journal-title":"J. Biol. Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1042\/bj3200595","article-title":"Human microglia convert l-tryptophan into the neurotoxin quinolinic acid","volume":"320","author":"Heyes","year":"1996","journal-title":"Biochem. J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1093\/brain\/124.5.1033","article-title":"Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection","volume":"124","author":"Heyes","year":"2001","journal-title":"Brain"},{"key":"B37","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1042\/bj2830633","article-title":"Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid","volume":"283","author":"Heyes","year":"1992","journal-title":"Biochem. J."},{"key":"B38","doi-asserted-by":"publisher","first-page":"296","DOI":"10.3389\/fnins.2020.00296","article-title":"Overview of brain-to-gut Axis exposed to chronic CNS bacterial infection(s) and a predictive urinary metabolic profile of a brain infected by Mycobacterium tuberculosis","volume":"14","author":"Isaiah","year":"2020","journal-title":"Front. Neurosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"593","DOI":"10.33549\/physiolres.930372","article-title":"Dynamics of cytokine production in human peripheral blood mononuclear cells stimulated by LPS, or infected by Borrelia","volume":"52","author":"Jansky","year":"2003","journal-title":"Physiological Res."},{"key":"B40","volume-title":"Information about tuberculosis","author":"Kanabus","year":"2020"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1124\/dmd.107.019075","article-title":"Aldehyde oxidase-catalyzed metabolism of N1-methylnicotinamide in vivo and in vitro in chimeric mice with humanized liver","volume":"36","author":"Kitamura","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"B42","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1189\/jlb.1204697","article-title":"Myeloperoxidase: friend and foe","volume":"77","author":"Klebanoff","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1203\/00006450-199110000-00006","article-title":"3-Hydroxyisobutyric aciduria: an inborn error of valine metabolism","volume":"30","author":"Ko","year":"1991","journal-title":"Pediatr. Res."},{"key":"B44","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-801918-4.00004-9","article-title":"Chapter 4 - metabolic pathways in the human body","volume-title":"Biochemistry for medical professionals","author":"Komoda","year":"2015"},{"key":"B45","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1093\/jat\/24.3.180","article-title":"The use of nuclear magnetic resonance spectroscopy in the detection of drug intoxication","volume":"24","author":"Komoroski","year":"2000","journal-title":"J. Anal. Toxicol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2010.00018","article-title":"Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats","volume":"18","author":"Kondoh","year":"2010","journal-title":"Front. Integr. Neurosci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1021\/pr300900b","article-title":"Hippurate: the natural history of a mammalian\u2013microbial cometabolite","volume":"12","author":"Lees","year":"2013","journal-title":"J. Proteome Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/0277-5379(83)90002-0","article-title":"Serum amino acids in weight-losing patients with cancer and tuberculosis","volume":"19","author":"Levin","year":"1983","journal-title":"Eur. J. Cancer Clin. Oncol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"883","DOI":"10.2174\/092986706776361058","article-title":"Cell Life versus cell longevity: the mysteries surrounding the NAD+ precursor nicotinamide","volume":"13","author":"Li","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"B50","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-383864-3.00013-2","article-title":"Chapter 13 - metabolism of amino acids","volume-title":"Human biochemistry","author":"Litwack","year":"2018"},{"key":"B51","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1007\/s11306-017-1261-4","article-title":"Urinary metabolite markers characterizing tuberculosis treatment failure","volume":"13","author":"Luies","year":"2017","journal-title":"Metabolomics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/s0732-8893(99)00007-3","article-title":"Malnutrition in tuberculosis","volume":"34","author":"Macallan","year":"1999","journal-title":"Diagnostic Microbiol. Infect. Dis."},{"key":"B53","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1042\/cs0940321","article-title":"Whole body protein metabolism in human pulmonary tuberculosis and undernutrition: evidence for anabolic block in tuberculosis","volume":"94","author":"Macallan","year":"1998","journal-title":"Clin. Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"7582948","DOI":"10.1155\/2019\/7582948","article-title":"Application of cerebrospinal fluid host protein biosignatures in the diagnosis of tuberculous meningitis in children from a high burden setting","volume":"2019","author":"Manyelo","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"B56","doi-asserted-by":"publisher","first-page":"017711","DOI":"10.1128\/JCM.01771-20","article-title":"Tuberculous meningitis: pathogenesis, immune responses, diagnostic challenges, and the potential of biomarker-based approaches","volume":"59","author":"Manyelo","year":"2021","journal-title":"J. Clin. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/S1473-3099(10)70138-9","article-title":"Tuberculous meningitis: a uniform case definition for use in clinical research","volume":"10","author":"Marais","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3389\/fnins.2017.00043","article-title":"Lactate shuttles in neuroenergetics\u2014homeostasis, allostasis and beyond","volume":"11","author":"Mason","year":"2017","journal-title":"Front. Neurosci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"534","DOI":"10.3389\/fnins.2017.00534","article-title":"Cerebrospinal fluid amino acid profiling of pediatric cases with tuberculous meningitis","volume":"11","author":"Mason","year":"2017","journal-title":"Front. Neurosci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"8","DOI":"10.17159\/sajs.2016\/20150086","article-title":"Tuberculous meningitis in infants and children: insights from nuclear magnetic resonance metabolomics","volume":"112","author":"Mason","year":"","journal-title":"S. Afr. J. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1007\/s11306-014-0741-z","article-title":"A hypothetical astrocyte\u2013microglia lactate shuttle derived from a 1H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis","volume":"11","author":"Mason","year":"2015","journal-title":"Metabolomics"},{"key":"B62","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1007\/s11306-016-1053-2","article-title":"A putative urinary biosignature for diagnosis and follow-up of tuberculous meningitis in children: outcome of a metabolomics study disclosing host\u2013pathogen responses","volume":"12","author":"Mason","year":"","journal-title":"Metabolomics"},{"key":"B63","doi-asserted-by":"publisher","first-page":"19780","DOI":"10.1038\/srep19780","article-title":"Urinary N-methylnicotinamide and \u03b2-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children","volume":"6","author":"Mayneris-Perxachs","year":"2016","journal-title":"Sci. Rep."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.5588\/ijtld.13.0017","article-title":"Changes in vitamin C and oxidative stress status during the treatment of tuberculous meningitis","volume":"17","author":"Miric","year":"2013","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"B65","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/s0009-8981(01)00608-8","article-title":"Methylamine in human urine","volume":"312","author":"Mitchell","year":"2001","journal-title":"Clin. Chim. acta"},{"key":"B66","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1586\/14737159.8.5.617","article-title":"Metabolomics-based methods for early disease diagnostics: a review","volume":"8","author":"Nagana Gowda","year":"2008","journal-title":"Expert Rev. Mol. diagn."},{"key":"B67","unstructured":"Roadmap towards ending TB in children and adolescents. Geneva\n            OrganizationW. H.\n          2018"},{"key":"B68","doi-asserted-by":"publisher","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B69","doi-asserted-by":"publisher","first-page":"42508","DOI":"10.1074\/jbc.M507380200","article-title":"High resolution 1H NMR-based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease","volume":"280","author":"Pears","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B70","first-page":"RA257","article-title":"Methylamine: a new endogenous modulator of neuron firing?","volume":"11","author":"Pirisino","year":"2005","journal-title":"Med. Sci. Monit."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1016\/S0891-5849(00)00229-X","article-title":"Myeloperoxidase-generated oxidants and atherosclerosis","volume":"28","author":"Podrez","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"B72","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12974-022-02387-0","article-title":"Nos2\u2212\/\u2212 mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis","volume":"19","author":"Poh","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"B73","doi-asserted-by":"publisher","first-page":"179","DOI":"10.2217\/bmm-2016-0287","article-title":"Metabolomics biomarkers for tuberculosis diagnostics: current status and future objectives","volume":"11","author":"Preez","year":"2017","journal-title":"Biomark. Med."},{"key":"B74","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3329\/bjp.v4i1.1443","article-title":"Oxidative metabolic changes in pleural fluid of tuberculosis patients","volume":"4","author":"Reddy","year":"2009","journal-title":"Bangladesh J. Pharmacol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"3767","DOI":"10.1038\/s41467-019-11783-9","article-title":"Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity","volume":"10","author":"Rohlwink","year":"2019","journal-title":"Nat. Commun."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1093\/cid\/cix540","article-title":"Biomarkers of cerebral injury and inflammation in pediatric tuberculous meningitis","volume":"65","author":"Rohlwink","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"B77","doi-asserted-by":"publisher","first-page":"3886","DOI":"10.1128\/JB.01767-07","article-title":"Functional characterization of a vitamin B12-dependent methylmalonyl pathway in Mycobacterium tuberculosis: implications for propionate metabolism during growth on fatty acids","volume":"190","author":"Savvi","year":"2008","journal-title":"J. Bacteriol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"697972","DOI":"10.1155\/2013\/697972","article-title":"Monocytes, peripheral blood mononuclear cells, and THP-1 cells exhibit different cytokine expression patterns following stimulation with lipopolysaccharide","volume":"10","author":"Schildberger","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"B79","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1097\/00075197-200007000-00008","article-title":"Tuberculosis, malnutrition and wasting","volume":"3","author":"Schwenk","year":"2000","journal-title":"Curr. Opin. Clin. Nutr. Metabolic Care"},{"key":"B80","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1016\/S0026-0495(96)90117-1","article-title":"l-Arabinose selectively inhibits intestinal sucrase in an uncompetitive manner and suppresses glycemic response after sucrose ingestion in animals","volume":"45","author":"Seri","year":"1996","journal-title":"Metab"},{"key":"B81","unstructured":"Structural insights into glycine reuptake inhibition\n            ShahsavarA.\n            StohlerP.\n            BourenkovG.\n            ZimmermannI.\n            SiegristM.\n            GubaW.\n          2020"},{"key":"B82","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1006\/neur.1995.0026","article-title":"CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients","volume":"4","author":"Shaw","year":"","journal-title":"Neurodegeneration"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1093\/clinchem\/41.8.1094","article-title":"Increased urinary excretion of analogs of Krebs cycle metabolites and arabinose in two brothers with autistic features","volume":"41","author":"Shaw","year":"","journal-title":"Clin. Chem."},{"key":"B84","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1021\/pr101054m","article-title":"1H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis","volume":"10","author":"Shin","year":"2011","journal-title":"J. Proteome Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"29","DOI":"10.2174\/1567202043480224","article-title":"Cell biological consequences of mitochondrial NADH: ubiquinone oxidoreductase deficiency","volume":"1","author":"Smeitink","year":"2004","journal-title":"Curr. Neurovasc. Res."},{"key":"B86","doi-asserted-by":"publisher","first-page":"E64","DOI":"10.1152\/ajpendo.00276.2003","article-title":"Branched-chain amino acid catabolism: unique segregation of pathway enzymes in organ systems and peripheral nerves","volume":"286","author":"Sweatt","year":"2004","journal-title":"Am. J. Physiology-Endocrinology Metabolism"},{"key":"B87","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.1016\/s0024-3205(02)02137-9","article-title":"Oxidant and antioxidant activities in childhood meningitis","volume":"71","author":"Tsukahara","year":"2002","journal-title":"Life Sci."},{"key":"B88","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3389\/neuro.02.009.2009","article-title":"Glycine and glycine receptor signalling in non-neuronal cells","volume":"2","author":"Van Den Eynden","year":"2009","journal-title":"Front. Mol. Neurosci."},{"key":"B89","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.cbpa.2004.08.013","article-title":"The role of analytical sciences in medical systems biology","volume":"8","author":"Van Der Greef","year":"2004","journal-title":"Curr. Opin. Chem. Biol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/0009-8981(71)90370-6","article-title":"Urinary and faecal excretion of metabolites of tyrosine and phenylalanine in a patient with cystic fibrosis and severely impaired amino acid absorption","volume":"31","author":"Van Der Heiden","year":"1971","journal-title":"Clin. Chim. Acta"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1111\/tmi.13134","article-title":"A treatment-support intervention evaluated in South African paediatric populations with HIV infection or tuberculous meningitis","volume":"23","author":"Van Elsland","year":"2018","journal-title":"Trop. Med. Int. Health"},{"key":"B92","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/S1473-3099(18)30053-7","article-title":"Cerebral tryptophan metabolism and outcome of tuberculous meningitis: an observational cohort study","volume":"18","author":"Van Laarhoven","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"B93","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/INF.0000000000000065","article-title":"Short intensified treatment in children with drug-susceptible tuberculous meningitis","volume":"33","author":"Van Toorn","year":"2014","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B94","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.spen.2014.01.006","article-title":"Update on the diagnosis and management of tuberculous meningitis in children","volume":"21","author":"Van Toorn","year":"2014","journal-title":"Semin. Pediatr. Neurol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"628","DOI":"10.5588\/ijtld.11.0648","article-title":"Value of different staging systems for predicting neurological outcome in childhood tuberculous meningitis","volume":"16","author":"Van Toorn","year":"2012","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"B96","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.jinf.2020.06.078","article-title":"Metabolic characterization of tuberculous meningitis in a South African paediatric population using 1H NMR metabolomics","volume":"81","author":"Van Zyl","year":"2020","journal-title":"J. Infect."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.3389\/fnagi.2022.1046066","article-title":"Systematic evaluation of urinary formic acid as a new potential biomarker for Alzheimer\u2019s disease","volume":"14","author":"Wang","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"B98","doi-asserted-by":"publisher","first-page":"e40221","DOI":"10.1371\/journal.pone.0040221","article-title":"Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients","volume":"7","author":"Weiner","year":"2012","journal-title":"PloS one"},{"key":"B106","volume-title":"Basic method validation","author":"Westgard","year":"2008"},{"key":"B99","volume-title":"W.H.O global tuberculosis report 2020","year":"2020"},{"key":"B100","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/1471-230X-10-108","article-title":"Differences in gut microbial metabolism are responsible for reduced hippurate synthesis in Crohn's disease","volume":"10","author":"Williams","year":"2010","journal-title":"BMC Gastroenterol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.parkreldis.2005.05.011","article-title":"Nicotinamide: a double edged sword","volume":"11","author":"Williams","year":"2005","journal-title":"Park. Relat. Disord."},{"key":"B102","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1093\/tropej\/fms031","article-title":"The changing profile of pediatric meningitis at a referral centre in Cape Town, South Africa","volume":"58","author":"Wolzak","year":"2012","journal-title":"J. Trop. Pediatr."},{"key":"B103","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1074\/mcp.M112.021816","article-title":"Identification and validation of urinary metabolite biomarkers for major depressive disorder","volume":"12","author":"Zheng","year":"2013","journal-title":"Mol. Cell Proteomics"},{"key":"B104","doi-asserted-by":"publisher","first-page":"5674","DOI":"10.3748\/wjg.15.5674","article-title":"Nicotinamide overload may play a role in the development of type 2 diabetes","volume":"15","author":"Zhou","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"2686","DOI":"10.3390\/ijerph15122686","article-title":"Metabolomics reveals metabolic changes caused by low-dose 4-Tert-Octylphenol in mice liver","volume":"15","author":"Zhou","year":"2018","journal-title":"Int. J. Environ. Res. Public Health"}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2024.1253983\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:41:23Z","timestamp":1710463283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2024.1253983\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,15]]},"references-count":106,"alternative-id":["10.3389\/fmolb.2024.1253983"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2024.1253983","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,15]]},"article-number":"1253983"}}