Cocaine-Enriched Oral Streptococcus parasanguinis Promotes Neuroimmune Dysfunction and Memory Impairment
Year: 2026
Type: preprint
Abstract: Chronic cocaine use is associated with neuroinflammation and cognitive dysfunction, but the underlying mechanisms remain unclear. We previously identified oral enrichment of Streptococcus parasanguinis (SP) and other species in individuals with cocaine use disorder (CUD), and here demonstrate that cocaine selectively enhanced SP growth in vitro . To investigate causality, antibiotic-pretreated wild-type C57BL/6 mice received chronic oral inoculation of SP, S. salivarius , Neisseria flavescens , or vehicle. SP-treated mice exhibited spatial memory impairment, increased brain IL-1β, and non-region-specific microglial activation, without detectable bacterial translocation into the brain. While amyloid-associated signaling changes were observed across all bacterial treatment groups, only SP induced cognitive deficits and neuroinflammation. Untargeted metabolomics identified distinct SP-associated oral-to-brain metabolite signatures, including cysteine S-sulfate (CSS) and altered histamine-associated metabolites. CSS and histamine induced neuroinflammatory and amyloid-associated responses in vitro . Together, these findings identify a cocaine-associated oral pathobiont that promotes neuroinflammation and neurodegeneration, suggesting a novel oral microbiome-brain axis in CUD.
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: green
Awards: G6207528334, Impacts of drug abuse-mediated inflammatory perturbations on affinity maturation of anti-CD4 autoantibodies and poor immune reconstitution from ART in HIV, Investigating the effect of oral microbiome on cognition in HIV-infected chronic cannabis users, MUSC Digestive Disease Research Core Center, Investigate Host Gene Isoforms Contributing to HIV Persistence in Cocaine Users
OpenAlex ID: W7165039403