Distinct cerebrospinal fluid microbiome dysbiosis associated with disease severity in tick-borne encephalitis

Background Tick-borne encephalitis is the most prevalent viral encephalitis in Europe, causing inflammation of the central nervous system (CNS) and often leading to persistent neurological complications. While alterations in microbial composition have been linked with neuroinflammation and disease progression, data on microbiota profiles in patients with tick-borne encephalitis virus (TBEV) infection are lacking. Methods Cerebrospinal fluid (CSF) samples were obtained, following informed consent, from patients with TBEV–associated meningitis (n = 25) or encephalitis (n = 25) and from uninfected controls (n = 13). Full-length 16S rRNA gene sequencing was performed to characterise bacterial community composition. Genus-level relative abundance profiles were analysed, and differential abundance testing was conducted using non-parametric statistics with false discovery rate correction. Enrichment analysis, LEfSe-like statistical approaches, and supervised multivariate modelling were applied to identify taxa associated with severity of the infection. Results Distinct alterations in microbial diversity and community composition were observed across TBE with neurological involvement and controls. Alpha-diversity analyses demonstrated increased diversity and richness in meningitis samples across Shannon, Simpson, Chao1, and observed species metrics, whereas encephalitis samples exhibited reduced richness compared with controls. Beta-diversity analysis revealed clear separation between controls and infected groups, with partial overlap between meningitis and encephalitis, indicating syndrome-associated shifts in community structure. Taxonomic composition analysis further identified differentially enriched taxa across groups, with a subset of Enterobacteriaceae-associated genera significantly enriched in encephalitis, consistent with a distinct microbial signature associated with increased disease severity. Conclusions These findings indicate that TBEV-associated meningitis and encephalitis are characterised by distinct CSF microbiome profiles rather than a uniform infection-related shift. The increased diversity and richness observed in meningitis, together with reduced richness and enrichment of specific genera in encephalitis, suggest a microbiome signature associated with more severe CNS involvement. Together, these results support the presence of disease severity–specific microbial dysbiosis in TBEV infection and highlight the possible relevance of CSF microbiota in the pathogenesis of neuroinflammatory disease.