- Oral and gut bacterial extracellular vesicles cross the blood-brain barrier, delivering bioactive cargo that can modulate host cells and drive CNS disease pathogenesis.
- Functional dichotomy: pathogen-derived BEVs promote neuropathology while probiotic and engineered BEVs confer protection and therapeutic potential.
- Clinical translation hindered by mechanistic gaps, biomarker validation, safety, standardisation and delivery challenges; research priorities include mechanistic studies and scalable engineering.
Microbiol Res. 2026 Aug 4;312:128661. doi: 10.1016/j.micres.2026.128661. Online ahead of print.
ABSTRACT
A growing body of evidence indicates that the oral and gut microbiota are closely linked to central nervous system (CNS) diseases, and their bacterial extracellular vesicles (BEVs) play a significant role in disease pathogenesis. BEVs can cross the blood-brain barrier, deliver bioactive cargo to host cells, and participate in disease processes. Notably, BEVs exhibit a functional dichotomy in which pathogen-derived BEVs promote neuropathology while probiotic-derived and engineered BEVs exert protective effects. In this review, we systematically examine this dual role of oral- and gut-derived BEVs in CNS diseases, covering their pathogenic mechanisms, protective and therapeutic effects, and emerging applications as diagnostic biomarkers. We also highlight key challenges limiting clinical translation and outline future directions for the field.
PMID:42561498 | DOI:10.1016/j.micres.2026.128661
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