Extracellular vesicles of Fusobacterium nucleatum induce anxiety and depression by triggering neuroinflammation via IL-1β

Fusobacterium nucleatum (Fn) is an opportunistic Gram-negative oral bacterium that is associated with periodontitis. Fn can induce inflammation outside of the oral cavity via bacterial translocation to other organs, and extracellular vesicles (EVs) released by the bacterium have been implicated in mediating this inflammation. However, the effects of Fn EVs on the brain have not been explored in detail. Here, we investigated the neuropathological effects of Fn EVs. Fn EVs induced neuroinflammation, characterized by microglial activation and alteration of inhibitory synaptic transmission, which was associated with anxiety- and depressive-like behaviors. Administration of Fn EVs increased IL-1β release, and pharmacological inhibition of IL-1β ameliorated the Fn EVs-induced behavioral abnormalities. Our data indicate that Fn EVs have the capacity to trigger neuroinflammation via the IL-1β pathway, contributing to depression and anxiety, highlighting the potential of Fn EVs to mediate pathogenic neuroinflammation via the microbiome-gut/oral-brain axis in neurological/psychiatric disorders.