{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:15:07Z","timestamp":1790792107961,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP20K10123"],"award-info":[{"award-number":["JP20K10123"]}]},{"name":"JSPS KAKENHI","award":["1864"],"award-info":[{"award-number":["1864"]}]},{"name":"JSPS KAKENHI","award":["2153"],"award-info":[{"award-number":["2153"]}]},{"name":"Dokkyo Medical University","award":["JP20K10123"],"award-info":[{"award-number":["JP20K10123"]}]},{"name":"Dokkyo Medical University","award":["1864"],"award-info":[{"award-number":["1864"]}]},{"name":"Dokkyo Medical University","award":["2153"],"award-info":[{"award-number":["2153"]}]},{"name":"Dokkyo Medical University","award":["JP20K10123"],"award-info":[{"award-number":["JP20K10123"]}]},{"name":"Dokkyo Medical University","award":["1864"],"award-info":[{"award-number":["1864"]}]},{"name":"Dokkyo Medical University","award":["2153"],"award-info":[{"award-number":["2153"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The involvement of oral bacteria in the pathogenesis of distant organs, such as the heart, lungs, brain, liver, and intestine, has been shown. We analyzed the distribution of bacterial species in the resected aortic valve by 16S rRNA metagenomic analysis and directly compared their gene sequences with those in the oral cavity. Thirty-two patients with aortic stenosis or aortic regurgitation who underwent aortic valve replacement were enrolled in this study. Antibody titer against periodontal pathogenic bacteria in the patient\u2019s serum was analyzed. The genetic background and distribution of bacterial species on subgingival plaque, the dorsal surface of the tongue, and the resected aortic valve were analyzed. Patients with aortic valve disease were shown to have more severe periodontal disease by the detection of antibodies against Socransky\u2019s red-complex bacteria of periodontitis. Bacterial DNA was detected in the aortic valves of 12 out of 32 patients. The genomic sequences of the V3-V4 region of the 16S rRNA in some bacteria isolated from the aortic valves of six patients who underwent metagenomic analysis were identical to those found in the oral cavity. The findings indicate that bacteria detected in the aortic valve may be introduced through oral dysbiosis, a condition characterized by an imbalance in the oral microbiota that increases the risk of periodontal disease and dental caries. Oral dysbiosis and the resulting potential bacteremia are associated with the pathogenesis of aortic valve diseases.<\/jats:p>","DOI":"10.3390\/microorganisms13071677","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T15:48:22Z","timestamp":1752680902000},"page":"1677","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oral Dysbiosis Is Associated with the Pathogenesis of Aortic Valve Diseases"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8975-5444","authenticated-orcid":false,"given":"Erika","family":"Yaguchi","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-6895","authenticated-orcid":false,"given":"Yuske","family":"Komiyama","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Inami","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, 880 Kitakoba Yashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4017-8503","authenticated-orcid":false,"given":"Ikuko","family":"Shibasaki","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Vascular Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0789-3273","authenticated-orcid":false,"given":"Tomoaki","family":"Shintani","sequence":"additional","affiliation":[{"name":"Center for Oral Clinical Examination, Hiroshima University Hospital; 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Hyodo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3177-0764","authenticated-orcid":false,"given":"Hideki","family":"Shiba","sequence":"additional","affiliation":[{"name":"Department of Biological Endodontics, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5872-4421","authenticated-orcid":false,"given":"Shinsuke","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotsugu","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Vascular Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-833X","authenticated-orcid":false,"given":"Shigeru","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, 880 Kitakoba Yashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5160-6892","authenticated-orcid":false,"given":"Chonji","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9838-6734","authenticated-orcid":false,"given":"Takahiro","family":"Wakui","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Kawamata","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Shimotsuga, Mibu 321-0293, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1113\/JP272427","article-title":"From focal sepsis to periodontal medicine: A century of exploring the role of the oral microbiome in systemic disease","volume":"595","author":"Kumar","year":"2017","journal-title":"J. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.tim.2020.11.004","article-title":"The oral host\u2013microbial interactome: An ecological chronometer of health?","volume":"29","author":"Freire","year":"2021","journal-title":"Trends Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/bs.aambs.2016.08.002","article-title":"The oral microbiome in health and its implication in oral and systemic diseases","volume":"97","author":"Caldas","year":"2016","journal-title":"Adv. Appl. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1007\/s00784-023-05053-8","article-title":"Metagenomic analysis of oral plaques and aortic valve tissues reveals oral bacteria associated with aortic stenosis","volume":"27","author":"Yoshida","year":"2023","journal-title":"Clin. Oral Investig."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pardo, A., Signoriello, A., Signoretto, C., Messina, E., Carelli, M., Tessari, M., De Manna, N.D., Rossetti, C., Albanese, M., and Lombardo, G. (2021). Detection of periodontal pathogens in oral samples and cardiac specimens in patients undergoing aortic valve replacement: A pilot study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10173874"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.amjmed.2016.10.005","article-title":"Aortic stenosis: Pathophysiology, diagnosis, and therapy","volume":"130","author":"Joseph","year":"2017","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1161\/CIRCRESAHA.121.318040","article-title":"Current therapeutic options in aortic stenosis","volume":"128","author":"Boskovski","year":"2021","journal-title":"Circ. Res."},{"key":"ref_8","first-page":"103","article-title":"Implication of the oral bacteria on the onset of infective endocarditis","volume":"41","author":"Hakata","year":"2014","journal-title":"Dokkyo J. Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1111\/jcpe.12935","article-title":"A new classification scheme for periodontal and peri-implant diseases and conditions\u2013introduction and key changes from the 1999 classification","volume":"45","author":"Caton","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/cei.13430","article-title":"Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke","volume":"200","author":"Nishi","year":"2020","journal-title":"Clin. Exp. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.peptides.2015.04.012","article-title":"A short history, principles, and types of ELISA, and our laboratory experience with peptide\/protein analyses using ELISA","volume":"72","author":"Aydin","year":"2015","journal-title":"Peptides"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Robeson, M.S., O\u2019Rourke, D.R., Kaehler, B.D., Ziemski, M., Dillon, M.R., Foster, J.T., and Bokulich, N.A. (2021). RESCRIPt: Reproducible sequence taxonomy reference database management. PLoS Comput. Biol., 17.","DOI":"10.1371\/journal.pcbi.1009581"},{"key":"ref_16","unstructured":"R Core Team (2023). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1080\/10543406.2011.578313","article-title":"A note on power and sample size calculations for the Kruskal-Wallis test for ordered categorical data","volume":"22","author":"Fan","year":"2012","journal-title":"J Biopharm. Stat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1574-6976.2008.00111.x","article-title":"Species divergence and the measurement of microbial diversity","volume":"32","author":"Lozupone","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, Y., Sun, F., Lin, W., and Zhang, S. (2022). AC-PCoA: Adjustment for confounding factors using principal coordinate analysis. PLoS Comput. Biol., 18.","DOI":"10.1371\/journal.pcbi.1010184"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yue, Y., and Hu, Y.J. (2022). Extension of PERMANOVA to Testing the Mediation Effect of the Microbiome. Genes, 13.","DOI":"10.1101\/2022.04.26.489586"},{"key":"ref_21","unstructured":"Oksanen, J., Simpson, G., Blanchet, F., Kindt, R., Legendre, P., Minchin, P., O\u2019Hara, R., Solymos, P., Stevens, M., and Szoecs, E. (2025, June 26). Vegan: Community Ecology Package, R package version 2.6-4; 2022. Available online: https:\/\/cran.r-project.org\/src\/contrib\/Archive\/vegan\/."},{"key":"ref_22","unstructured":"Japanese Ministry of Health, Labour and Welfare (2016). Heisei 28 Nen Shikasikkanjittaityousa [Dental Disease Survey]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1034\/j.1600-0757.2002.280102.x","article-title":"Dental biofilms: Difficult therapeutic targets","volume":"28","author":"Socransky","year":"2002","journal-title":"Periodontol. 2000"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ijcard.2017.09.001","article-title":"Periodontal bacteria DNA findings in human cardiac tissue\u2014Is there a link of periodontitis to heart valve disease?","volume":"251","author":"Ziebolz","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"636893","DOI":"10.1155\/2014\/636893","article-title":"Periodontitis as a risk factor of atherosclerosis","volume":"2014","author":"Bartova","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Olsen, I., Taubman, M.A., and Singhrao, S.K. (2016). Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer\u2019s disease. J. Oral Microbiol., 8.","DOI":"10.3402\/jom.v8.33029"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/prd.12304","article-title":"Mechanisms underlying the association between periodontitis and atherosclerotic disease","volume":"83","author":"Schenkein","year":"2020","journal-title":"Periodontol. 2000"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.ijcard.2014.04.201","article-title":"Molecular analysis of oral bacteria in dental biofilm and atherosclerotic plaques of patients with vascular disease","volume":"174","author":"Fernandes","year":"2014","journal-title":"Int. J Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.4103\/0377-4929.134704","article-title":"Periodontal pathogens in atheromatous plaque","volume":"57","author":"Rath","year":"2014","journal-title":"Indian J. Pathol. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.hlc.2018.05.102","article-title":"Periodontal disease, systemic inflammation and the risk of cardiovascular disease","volume":"27","year":"2018","journal-title":"Heart Lung Circ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1136\/jnnp-2012-304635","article-title":"The connection between ruptured cerebral aneurysms and odontogenic bacteria","volume":"84","author":"Pyysalo","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/cei\/uxac094","article-title":"Periapical lesion following Cnm-positive Streptococcus mutans pulp infection worsens cerebral hemorrhage onset in an SHRSP rat model","volume":"210","author":"Taniguchi","year":"2022","journal-title":"Clin. Exp. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1161\/STROKEAHA.120.029607","article-title":"Oral carriage of Streptococcus mutans harboring the cnm gene relates to an increased incidence of cerebral microbleeds","volume":"51","author":"Hosoki","year":"2020","journal-title":"Stroke"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2067","DOI":"10.1097\/MD.0000000000002067","article-title":"Molecular Analysis of Oral Bacteria in Heart Valve of Patients With Cardiovascular Disease by Real-Time Polymerase Chain Reaction","volume":"94","author":"Oliveira","year":"2015","journal-title":"Medicine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1399-302X.2008.00479.x","article-title":"Detection of oral bacteria in cardiovascular specimens","volume":"24","author":"Nakano","year":"2009","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0003-4975(03)01454-1","article-title":"Role of oral bacterial flora in calcific aortic stenosis: An animal model","volume":"77","author":"Cohen","year":"2004","journal-title":"Ann. Thorac. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1177\/039463201002300218","article-title":"Examination of periodontal pathogens in stenotic valve specimens and in whole blood samples in patients affected by aortic valve stenosis and chronic periodontitis","volume":"23","author":"Raffaelli","year":"2010","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1254\/jphs.09R26FM","article-title":"Roles of oral bacteria in cardiovascular diseases\u2014From molecular mechanisms to clinical cases: Porphyromonas gingivalis is the important role of intimal hyperplasia in the aorta","volume":"113","author":"Hokamura","year":"2010","journal-title":"J. Pharmacol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.ijom.2020.10.004","article-title":"Oral management with polaprezinc solution reduces adverse events in hematopoietic stem cell transplantation patients","volume":"50","author":"Komiyama","year":"2021","journal-title":"Int. J. Oral Maxillofac. Surg."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/7\/1677\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:10:54Z","timestamp":1760033454000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/7\/1677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["microorganisms13071677"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13071677","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,16]]}}}