{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:36:16Z","timestamp":1793158576194,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Microbiology","reference-count":84,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"Sunstar Inc., Osaka, Japan"},{"name":"University at Buffalo, State University of New York","award":["start-up funds"],"award-info":[{"award-number":["start-up funds"]}],"id":[{"id":"https:\/\/ror.org\/01y64my43","id-type":"ROR","asserted-by":"crossref"}]},{"name":"UAE-NIH Collaborative Research Grant","award":["AJF-NIH-25-KU"],"award-info":[{"award-number":["AJF-NIH-25-KU"]}]},{"name":"National Institute of Dental and Craniofacial Research","award":["R01DE012085"],"award-info":[{"award-number":["R01DE012085"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Dental and Craniofacial Research","award":["K99DE034829"],"award-info":[{"award-number":["K99DE034829"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Khalifa University","id":[{"id":"https:\/\/ror.org\/05hffr360","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.<\/jats:p>","DOI":"10.64898\/2026.09.24.754177","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:46:02Z","timestamp":1790606762000},"source":"Crossref","is-referenced-by-count":0,"title":["A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1145-6308","authenticated-orcid":false,"given":"Lu","family":"Li","sequence":"first","affiliation":[{"name":"UB Microbiome Center, University at Buffalo, SUNY, Buffalo, NY, USA"},{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moemen","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates"},{"name":"Department of Engineering Mathematics and Physics, Faculty of Engineering, Alexandria University, Alexandria, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Falkner","sequence":"additional","affiliation":[{"name":"UB Microbiome Center, University at Buffalo, SUNY, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Genco","sequence":"additional","affiliation":[{"name":"UB Microbiome Center, University at Buffalo, SUNY, Buffalo, NY, USA"},{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0610-6132","authenticated-orcid":false,"given":"Yijun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA"},{"name":"Department of Computer Science and Engineering, University at Buffalo, SUNY, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Wactawski-Wende","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Environmental Health, University at Buffalo, SUNY, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Buck","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haralampos","family":"Hatzikirou","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Khalifa University, Abu Dhabi, United Arab Emirates"},{"name":"Center for Information Services and High Performance Computing, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia I.","family":"Diaz","sequence":"additional","affiliation":[{"name":"UB Microbiome Center, University at Buffalo, SUNY, Buffalo, NY, USA"},{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"6","key":"2026102720100561000_2026.09.24.754177v2.1","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/j.1600-0765.1978.tb00209.x","article-title":"The natural history of periodontal disease in man. 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