{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:05:24Z","timestamp":1790996724626,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose:<\/jats:title>\n            <jats:p>\n              Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with\n              <jats:italic>Streptococcus mutans<\/jats:italic>\n              expressing Cnm, a collagen-binding protein in the oral cavity.\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              is a major pathogen responsible for dental caries. Repeated challenge with\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              harboring the\n              <jats:italic>cnm<\/jats:italic>\n              gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of\n              <jats:italic>cnm<\/jats:italic>\n              -positive\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              to the development of CMB.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              We retrospectively investigated patients with stroke receiving oral microbiological examination and head 3T magnetic resonance imaging evaluations twice in the period 2014 to 2019, allowing &gt;180-day interval. Patients with\n              <jats:italic>cnm<\/jats:italic>\n              -positive\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              were compared with those without. Quasi-Poisson regression models were used to explore associations between\n              <jats:italic>cnm<\/jats:italic>\n              -positive\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              and the increase in number of CMB between the 2 magnetic resonance imaging scans.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              A total of 111 patients were identified; 21 (19%) with\n              <jats:italic>cnm<\/jats:italic>\n              -positive\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              and 90 (81%) without. Clinical history, including blood pressure and the use of antithrombotic agents, were comparable between the 2 groups. New CMB were more commonly observed in patients with\n              <jats:italic>cnm<\/jats:italic>\n              -positive\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              (52% versus 23%;\n              <jats:italic>P<\/jats:italic>\n              =0.008). The incidence of CMB was significantly higher in the group with\n              <jats:italic>cnm<\/jats:italic>\n              -positive\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              , especially in deep areas, (incidence rate ratios [95% CI], 5.1 [1.9\u201313.6] for CMB in any brain region; 15.0 [5.4\u201342.0] for deep CMB), which persisted after adjusting for age, sex, hypertension, and renal impairment (4.7 [1.8\u201311.9] for CMB in any brain region; 13.9 [4.3\u201344.5] for deep CMB).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              This study demonstrates that\n              <jats:italic>cnm<\/jats:italic>\n              -positive\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              is associated with an increased incidence of CMB. Treatment for\n              <jats:italic>cnm<\/jats:italic>\n              -positive\n              <jats:italic>S.<\/jats:italic>\n              <jats:italic>mutans<\/jats:italic>\n              infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.120.029607","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T10:00:48Z","timestamp":1604570448000},"page":"3632-3639","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Oral Carriage of\n            <i>Streptococcus mutans<\/i>\n            Harboring the\n            <i>cnm<\/i>\n            Gene Relates to an Increased Incidence of Cerebral Microbleeds"],"prefix":"10.1161","volume":"51","author":[{"given":"Satoshi","family":"Hosoki","sequence":"first","affiliation":[{"name":"Department of Neurology (S.H., S.S., S.T., H. Ishiyama, T.Y., S.I., H. Ikenouchi, Y.H., M.I.), National Cerebral and Cardiovascular Center, Suita, Japan."},{"name":"Department of Neurology, Keio University School of Medicine, Tokyo, Japan (S.H., J.N., N.S., K.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8608-058X","authenticated-orcid":true,"given":"Satoshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Neurology (S.H., S.S., S.T., H. Ishiyama, T.Y., S.I., H. Ikenouchi, Y.H., M.I.), National Cerebral and Cardiovascular Center, Suita, Japan."},{"name":"Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan (S.S., R.N., K.N.)."},{"name":"Faculty of Medicine, University of Southampton, United Kingdom (S.S., R.O.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7092-2121","authenticated-orcid":true,"given":"Shuichi","family":"Tonomura","sequence":"additional","affiliation":[{"name":"Department of Neurology (S.H., S.S., S.T., H. Ishiyama, T.Y., S.I., H. Ikenouchi, Y.H., M.I.), National Cerebral and Cardiovascular Center, Suita, Japan."},{"name":"Department of Neurology, Graduate School of Medicine, Kyoto University, Japan (S.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0071-7338","authenticated-orcid":true,"given":"Hiroyuki","family":"Ishiyama","sequence":"additional","affiliation":[{"name":"Department of Neurology (S.H., S.S., S.T., H. Ishiyama, T.Y., S.I., H. Ikenouchi, Y.H., M.I.), National Cerebral and Cardiovascular Center, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3178-8171","authenticated-orcid":true,"given":"Takeshi","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Department of Neurology (S.H., S.S., S.T., H. Ishiyama, T.Y., S.I., H. Ikenouchi, Y.H., M.I.), National Cerebral and Cardiovascular Center, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Neurology (S.H., S.S., S.T., H. Ishiyama, T.Y., S.I., H. Ikenouchi, Y.H., M.I.), National Cerebral and Cardiovascular Center, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Ikenouchi","sequence":"additional","affiliation":[{"name":"Department of Neurology (S.H., S.S., S.T., H. Ishiyama, T.Y., S.I., H. 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