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We previously identified oral enrichment of\n                  <jats:italic>Streptococcus parasanguinis<\/jats:italic>\n                  (SP) and other species in individuals with cocaine use disorder (CUD), and here demonstrate that cocaine selectively enhanced SP growth\n                  <jats:italic>in vitro<\/jats:italic>\n                  . To investigate causality, antibiotic-pretreated wild-type C57BL\/6 mice received chronic oral inoculation of SP,\n                  <jats:italic>S. salivarius<\/jats:italic>\n                  ,\n                  <jats:italic>Neisseria flavescens<\/jats:italic>\n                  , or vehicle. SP-treated mice exhibited spatial memory impairment, increased brain IL-1\u03b2, 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\n                  <jats:italic>in vitro<\/jats:italic>\n                  . Together, these findings identify a cocaine-associated oral pathobiont that promotes neuroinflammation and neurodegeneration, suggesting a novel oral microbiome-brain axis in CUD.\n                <\/jats:p>","DOI":"10.64898\/2026.06.12.731966","type":"posted-content","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T14:45:21Z","timestamp":1781707521000},"source":"Crossref","is-referenced-by-count":0,"title":["Cocaine-Enriched Oral\n                  <i>Streptococcus parasanguinis<\/i>\n                  Promotes Neuroimmune Dysfunction and Memory Impairment"],"prefix":"10.64898","author":[{"given":"Douglas","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"},{"name":"University of South Carolina, School of Medicine, Columbia, SC 29208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabinda","family":"Salman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad","family":"Noorani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Benowitz","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamala","family":"Sundararaj","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Shelley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwu","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Fitting","sequence":"additional","affiliation":[{"name":"Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel D.","family":"Penrod","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Medical University of South Carolina, Charleston, USA, 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-053X","authenticated-orcid":false,"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, USA, 29425"},{"name":"Ralph H. 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