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We previously found an enrichment of oral\n                      <jats:italic>Actinomyces<\/jats:italic>\n                      species in chronic cannabis smokers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Wild\u2010type C57BL\/6 mice were orally inoculated with\n                      <jats:italic>Actinomyces<\/jats:italic>\n                      species following antibiotic preconditioning and assessed using behavioral assays, multi\u2010tissue cytokine profiling, single\u2010cell RNA sequencing, metabolomics, and biochemical analyses. Selected metabolites were tested in neuronal cells in vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Oral inoculation with cannabis use\u2010associated\n                      <jats:italic>Actinomyces<\/jats:italic>\n                      species, especially\n                      <jats:italic>A. meyeri<\/jats:italic>\n                      , in mice was accompanied by anxiety\u2010like behaviors, alterations in mitochondrial pathways, and reduced GABAergic markers, without evidence of bacterial brain translocation, changes in the canonical proinflammatory cytokines measured in this study, or memory decline. Notably, integrated oral and brain metabolomic analyses prioritized arginine and argininosuccinate as candidate mediators associated with Actinomyces exposure for further investigation. Selected metabolites associated with\n                      <jats:italic>Actinomyces<\/jats:italic>\n                      exposure altered mitochondrial function and oxidative stress in neuronal cells in vitro, supporting their potential role in mediating the observed molecular changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these results suggest that oral microbiome\u2010associated metabolites may contribute to behavioral alterations through mechanisms involving mitochondrial remodeling and altered GABAergic pathways, supporting further investigation of the oral\u2010brain metabolic axis in neuropsychiatric disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/advs.78144","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:02:30Z","timestamp":1792033350000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral\n                    <i>Actinomyces<\/i>\n                    Species Exposure is Associated with Anxiety\u2010Like Behavior, Mitochondrial Remodeling, and Altered GABAergic Pathways"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-703X","authenticated-orcid":false,"given":"Tabinda","family":"Salman","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Immunology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwu","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0697-8283","authenticated-orcid":false,"given":"Douglas","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9946-3746","authenticated-orcid":false,"given":"Arshad A.","family":"Noorani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Ralph H. Johnson VA Medical Center  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-7333","authenticated-orcid":false,"given":"Bogdan","family":"Bordieanu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-8850","authenticated-orcid":false,"given":"Zhi\u2010wei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9752-2128","authenticated-orcid":false,"given":"Rachel D.","family":"Penrod","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8610-2029","authenticated-orcid":false,"given":"Hongxu","family":"Xian","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-3133","authenticated-orcid":false,"given":"Sylvia","family":"Fitting","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9487-0119","authenticated-orcid":false,"given":"Peter W.","family":"Kalivas","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Medical University of South Carolina  Charleston South Carolina USA"}],"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 South Carolina USA"},{"name":"Ralph H. 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