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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).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    and depleted\n                    <jats:italic>Fusobacterium, Neisseria,<\/jats:italic>\n                    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.\n                    <jats:italic>S. parasanguinis<\/jats:italic>\n                    , but not cocaine alone, induced IL-1\u03b2 and TNF-\u03b1 production in human primary monocytes\n                    <jats:italic>in vitro<\/jats:italic>\n                    . scRNAseq further revealed innate immune activation, impaired T cell function, and heightened susceptibility to infection in CUD.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This pilot 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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.03.686400","type":"posted-content","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T07:30:18Z","timestamp":1762327818000},"source":"Crossref","is-referenced-by-count":1,"title":["Pilot study characterizing oral-to-blood microbial DNA translocation in individuals with current cocaine use disorder"],"prefix":"10.64898","author":[{"given":"Douglas","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, 29425, USA"},{"name":"Ralph H. 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