Cerebrospinal fluid metagenomic next-generation sequencing for culture-negative anaerobic central nervous system infection involving Prevotella oris: attribution challenges in low-biomass specimens

Abstract

Anaerobic central nervous system (CNS) infections are uncommon but diagnostically difficult because fastidious organisms may be suppressed by empirical antimicrobial therapy and conventional cultures may remain negative. Cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) can recover microbial nucleic acids in this setting, but low microbial biomass creates a central attribution problem: a detected organism may represent active infection, introduced commensal DNA, laboratory background, or bioinformatic misclassification. This narrative Mini Review uses Prevotella oris as a representative oral anaerobe to examine that problem. We synthesize evidence on low-biomass CSF specimen processing and sequencing strategies, including nanopore sequencing, whole-genome amplification, and targeted approaches, alongside contamination control, sequence-level and taxonomic credibility, host-response immunology, neuroimaging and source concordance, antimicrobial timing, and discordant clinical scenarios. We then organize these established principles into an expert-informed two-step pathway that separates technical signal credibility from clinical attribution and explicitly preserves an indeterminate state when evidence conflicts. P. oris is positioned as a useful model of the plausible contaminant paradox rather than as a pathogen with a unique CNS phenotype. We also outline syndrome-based management, source control, and treatment-duration principles. The framework is conceptual and non-validated; its purpose is transparent reasoning and reporting, not diagnostic scoring or probability estimation.