Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population

Area of Science:

• * Biochemistry and Molecular Biology
• * Pediatric Infectious Diseases
• * Metabolomics

Background:

• * Tuberculous meningitis (TBM) is a severe form of tuberculosis with significant neurological complications and mortality, particularly in children.
• * Limited understanding exists regarding the metabolic alterations associated with pediatric TBM.
• * Non-invasive diagnostic markers are crucial for early TBM detection in children.

Purpose of the Study:

• * To identify characteristic urinary metabolic markers differentiating severe pediatric TBM cases from controls.
• * To investigate the metabolic pathways affected in pediatric TBM.
• * To establish a potential biosignature for pediatric TBM diagnosis.

Main Methods:

• * Untargeted 1H NMR-based metabolomics analysis of urine samples from pediatric TBM cases (n=13) and controls (n=44).
• * Statistical analysis using MetaboAnalyst (v5.0) to identify significant metabolites.
• * Categorization of identified metabolites into affected metabolic pathways.

Main Results:

• * Identification of 29 characteristic urinary metabolites in pediatric TBM patients.
• * Six dysregulated metabolic pathways were identified: tryptophan catabolism, amino acid metabolism, energy production, gut microbiota metabolism, ketoacidosis, and nitrogen excretion.
• * These metabolites provide insights into the metabolic signature of advanced TBM in children.

Conclusions:

• * A distinct urinary metabolic profile characterizes pediatric TBM.
• * The identified metabolites and pathways can serve as potential non-invasive biomarkers for pediatric TBM.
• * This research offers novel biological insights into TBM's metabolic impact on children.