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

Background: Cocaine disrupts gut barriers in animal models, potentially enabling microbial translocation and inflammation in the periphery and central nervous system (CNS), but its direct role in inducing inflammation remains controversial. This study aimed to determine if the oral cavity is a source of circulating microbial DNA translocation in individuals with current cocaine use disorder (CUD). Results: A cross-sectional case-control study was conducted, comparing CUD and demographically matched non-drug controls. Ten CUD (via smoking or vaping) and 24 controls provided paired saliva and blood samples. Microbial 16S rRNA V4 region was sequenced in isolated microbial DNA from saliva and plasma. Single-cell RNA sequencing (scRNAseq) was analyzed in human peripheral blood mononuclear cells. Saliva from CUD, but not plasma, exhibited reduced alpha diversity and altered beta diversity, characterized by enriched Conclusions: This is the first study demonstrating that CUD via smoking or snorting exhibited oral microbial dysbiosis and selective oral-to-blood microbial translocation in vivo. These findings suggest that a compromised oral-to-blood barrier, rather than cocaine itself, promotes immune perturbations in CUD.