Cannabis-enriched oral Actinomyces induces anxiety-like behavior via impairing mitochondria and GABA signaling
Year: 2025
Type: preprint
Abstract: ABSTRACT The human oral microbiome is increasingly recognized as a contributor to brain health, yet its mechanisms remain unclear. Our previous work revealed that oral Actinomyces species was enriched in chronic cannabis smokers. Here, we show oral inoculation of cannabis use-associated Actinomyces species, especially A. meyeri , to wild-type C57BL/6 mice leads to anxiety-like behaviors, non-region-specific microglia activation, mitochondrial dysfunction, and reduced GABAergic neurotransmission, without evidence of bacterial translocation to the brain, neuroinflammation, and memory decline. Notably, Actinomyces species-producing metabolites, i.e., arginine and argininosuccinate, were increased in both oral swabs and brain following inoculation in vivo . These Actinomyces species-producing metabolites induced mitochondrial dysfunction and oxidative stress in neurons in vitro , indicating a neuropathogenic role and aligning with reduced GABAergic neurotransmission in vivo. Together, these results suggest that oral cannabis-associated dysbiosis impacts behavior through mitochondrial stress and impaired inhibitory signaling, indicating the oral–brain metabolic axis is potentially consequential in neuropsychiatric disorders. Teaser Chronic heavy cannabis use-enriched oral bacteria can drive anxiety and neuropathogenesis in mice. Highlights ◦ Cannabis-associated oral Actinomyces enrichment induces anxiety-like behavior in mice ◦ Microglial activation occurs without neuroinflammation (IL-1β, TNF-α, and IL-6) ◦ Mitochondrial hyperactivation and reduced inhibitory GABAergic signaling Graphical Abstract
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4416550311