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

Douglas Johnson, Kamala Sundararaj, S. Subramanian, Ya-Xin Qiu, Iniyan Samuel, Da Cheng, Tabinda Salman, Zhen-Wu Luo et al.

bioRxiv, 2025

1 citation

Abstract

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 Streptococcus and depleted Fusobacterium, Neisseria, and other taxa relative to controls. Controls exhibited low to undetectable microbial translocation in plasma. By contrast, plasma displayed CUD-specific oral enrichment of several Streptococcal species and evidence of translocation into the bloodstream. S. parasanguinis, but not cocaine alone, induced IL-1β and TNF-α production in human primary monocytes in vitro. scRNAseq further revealed innate immune activation, impaired T cell function, and heightened susceptibility to infection in CUD. Conclusions This pilot study…

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Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.

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