Dynamic Metabolomic Landscape of the Murine Brain Across Acute to Chronic Stages of Borrelia garinii Infection

Abstract

Lyme neuroborreliosis (LNB), caused by Borrelia garinii, often leads to persistent neurological deficits, yet early diagnosis remains insensitive and the temporal metabolic changes in the infected brain are largely unexplored. In this study, a murine model of B. garinii infection was established using 80 female BALB/c mice, and brain tissues were collected at acute 7 (days post-infection, DPI), mid- (15 and 21 DPI), and chronic (30 DPI) stages for untargeted gas chromatography–time-of-flight mass spectrometry (GC-TOF-MS) metabolomics. Thirty-one differential metabolites were identified, with downregulated metabolites predominating acutely and upregulated metabolites prevailing chronically. Twelve common metabolites, including creatine, lysine, and galactose derivatives, were consistently altered. KEGG analysis revealed disrupted amino acid metabolism, particularly valine, leucine, and isoleucine biosynthesis (ko00290), arginine and proline metabolism (ko00330), and aminoacyl-tRNA biosynthesis (ko00970). ROC analysis identified five candidate biomarkers, hydroxylamine, 2,3-dihydroxypyridine, galactose 1, galactose 2, and monostearin, with high diagnostic accuracy. This study provides a comprehensive temporal metabolomic landscape of the brain during B. garinii infection, revealing time-dependent metabolic reprogramming with sustained disruptions in amino acid and energy metabolism, and offering candidate biomarkers for improved diagnosis of central nervous system involvement in Lyme disease.