Metabolomics of cerebrospinal fluid in pediatric neuroborreliosis: unraveling candidate immunometabolic signatures and diagnostic potential.

BACKGROUND: Neuroborreliosis (LNB) poses a significant diagnostic challenge in paediatrics due to its non-specific clinical presentation and the limited sensitivity of standard tests. Metabolomics offers the possibility of direct insight into the biochemical changes occurring in the central nervous system during infection. OBJECTIVE: The aim of the study was to characterise the metabolic profile of paired serum and cerebrospinal fluid (CSF) in children with LNB to identify candidate immunometabolic signatures associated with the infection. METHODS: Samples were analysed using NMR spectroscopy and LC-MS/MS. Data gaps were filled using a Random Forest algorithm, followed by univariate and multivariate statistical tests (PLS-DA) and pathway enrichment analysis based on the KEGG database. RESULTS: Profound dysregulation of purine metabolism was demonstrated, manifested by elevated concentrations of hypoxanthine, xanthine and uric acid, which may reflect a combination of non-specific infection-related responses, oxidative stress, and potentially the pathogen's metabolic demand for host purines. Significant changes were observed in the biosynthesis of aromatic amino acids (particularly L-tyrosine) and in glycerophospholipid metabolism, suggesting damage to the blood-brain barrier. In CSF, alterations in choline and glutamate levels were identified as candidate metabolic signatures potentially associated with neuroinflammation and excitotoxicity. CONCLUSIONS: Metabolomic analysis enables precise mapping of the biochemical response in paediatric LNB. The identified abnormalities in purine metabolism, neuroinflammation and cell membrane integrity represent a promising starting point for future biomarker discovery research.