Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population
Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12 years). Little is known of the associated metabolic changes. This study aimed to identify characteristic metabolic markers that differentiate se...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1253983/full |
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| author | Simon Isaiah Du Toit Loots Mari van Reenen Regan Solomons Sabine van Elsland Sabine van Elsland A. Marceline Tutu van Furth Martijn van der Kuip Shayne Mason |
| author_facet | Simon Isaiah Du Toit Loots Mari van Reenen Regan Solomons Sabine van Elsland Sabine van Elsland A. Marceline Tutu van Furth Martijn van der Kuip Shayne Mason |
| author_sort | Simon Isaiah |
| collection | DOAJ |
| description | Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12 years). 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–metabolic 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. |
| first_indexed | 2024-04-24T23:48:38Z |
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| id | doaj.art-50d03792470f4df6a44a2f35c273eabd |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-24T23:48:38Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-50d03792470f4df6a44a2f35c273eabd2024-03-15T04:40:59ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2024-03-011110.3389/fmolb.2024.12539831253983Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric populationSimon Isaiah0Du Toit Loots1Mari van Reenen2Regan Solomons3Sabine van Elsland4Sabine van Elsland5A. Marceline Tutu van Furth6Martijn van der Kuip7Shayne Mason8Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South AfricaHuman Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South AfricaHuman Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South AfricaDepartment of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDepartment of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaMRC Centre for Global Infectious Disease Analysis, Imperial College London, London, United KingdomVrije Universiteit, Pediatric Infectious Diseases and Immunology, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, NetherlandsVrije Universiteit, Pediatric Infectious Diseases and Immunology, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, NetherlandsHuman Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South AfricaTuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12 years). 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–metabolic 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.https://www.frontiersin.org/articles/10.3389/fmolb.2024.1253983/fullurinemetabolicpaediatrictuberculous meningitis (TBM)untargeted metabolomicsProton nuclear magnetic resonance (1H NMR) spectroscopy |
| spellingShingle | Simon Isaiah Du Toit Loots Mari van Reenen Regan Solomons Sabine van Elsland Sabine van Elsland A. Marceline Tutu van Furth Martijn van der Kuip Shayne Mason Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population Frontiers in Molecular Biosciences urine metabolic paediatric tuberculous meningitis (TBM) untargeted metabolomics Proton nuclear magnetic resonance (1H NMR) spectroscopy |
| title | Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population |
| title_full | Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population |
| title_fullStr | Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population |
| title_full_unstemmed | Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population |
| title_short | Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population |
| title_sort | urinary metabolic characterization of advanced tuberculous meningitis cases in a south african paediatric population |
| topic | urine metabolic paediatric tuberculous meningitis (TBM) untargeted metabolomics Proton nuclear magnetic resonance (1H NMR) spectroscopy |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1253983/full |
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