Dynamic metabolomic landscape of the murine brain across acute to chronic stages of Borrelia garinii infection
Abstract
Abstract Background Lyme neuroborreliosis (LNB), caused by Borrelia garinii , is a severe complication of Lyme disease that often leads to persistent neurological deficits. Current diagnostic approaches lack sensitivity in early stages and fail to capture the dynamic metabolic changes occurring within the infected central nervous system. While metabolomics has emerged as a powerful tool for biomarker discovery in Lyme disease, the temporal metabolic landscape of the brain during B. garinii infection remains largely unexplored. Results A murine model of B. garinii infection was established using female BALB/c mice. Brain tissues were collected at acute (7 days post-infection, DPI), mid- (15 and 21 DPI), and chronic (30 DPI) stages. Untargeted metabolomics was performed using gas chromatography–time-of-flight mass spectrometry (GC-TOF-MS). A total of 31 differential metabolites were identified in the brain across infection stages. Temporal analysis revealed a predominance of downregulated metabolites at acute infection (7 DPI) and a shift toward upregulated metabolites at chronic stages (21–30 DPI). Twelve common differential metabolites were consistently altered across all time points, including creatine, lysine, and galactose derivatives. KEGG enrichment analysis identified significant disruptions in amino acid metabolism, particularly valine, leucine, and isoleucine biosynthesis (ko00290), arginine and proline metabolism (ko00330), and aminoacyl-tRNA biosynthesis (ko00970).…
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