Characterize Oral-to-Blood Microbial DNA Translocation in Individuals with Cocaine Use Disorder.

Area of Science:

• Microbiology
• Immunology
• Oral Health

Background:

• Cocaine's impact on gut barriers and inflammation is debated.
• Previous research suggests potential microbial translocation and systemic inflammation in cocaine users.
• The oral cavity's role in cocaine-associated inflammation is not well understood.

Purpose of the Study:

• To investigate if the oral cavity is a source of microbial DNA translocation in individuals with cocaine use disorder (CUD).
• To explore the relationship between oral microbiome changes, microbial translocation, and immune responses in CUD.

Main Methods:

• Cross-sectional case-control study comparing CUD individuals and controls.
• Paired saliva and blood samples analyzed for microbial 16S rRNA V4 region.
• Single-cell RNA sequencing (scRNAseq) used on peripheral blood mononuclear cells.
• In vitro experiments assessed cocaine's effect on oral bacteria growth and immune cell activation.

Main Results:

• CUD individuals showed oral microbial dysbiosis with enriched *Streptococcus* and depleted other taxa.
• Plasma *Streptococcus* species were enriched in CUD and showed evidence of translocation.
• Cocaine enhanced *S. parasanguinis* growth in vitro; this species induced pro-inflammatory cytokines.
• scRNAseq revealed innate immune activation and impaired T cell function in CUD.

Conclusions:

• This study is the first to demonstrate oral microbial dysbiosis and oral-to-blood translocation in CUD.
• A compromised oral-to-blood barrier, not cocaine directly, appears to drive immune perturbations in CUD.
• Findings highlight the oral cavity as a critical factor in cocaine-associated inflammation and health complications.