{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:47:20Z","timestamp":1781286440073,"version":"3.54.1"},"reference-count":27,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Procter & Gamble Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This research examined the effects of daily application of an oral hygiene regimen on the subgingival microbiome over 24 months. Generally healthy adults (107 enrolled, 87 completed) with early periodontitis used a home-care regimen (stannous fluoride paste, cetylpyridinium chloride rinse, power toothbrush, and floss) or usual care (control). Subgingival plaque samples were analyzed enzymatically for bacterial toxins. TLR ligands were measured using TLR-SEAP and TLR-ATP assays. Proinflammatory cytokines and metalloproteinases were quantified via immunoassays. Subgingival DNA was sequenced using a shotgun approach to assess microbial diversity. Increasing levels of bacteria, toxins, TLR activation, inflammatory cytokines, and MMPs were observed for periodontitis versus gingivitis and gingivitis versus healthy sites. The regimen significantly reduced levels of the critical proinflammatory cytokine IL-1\u03b2, as well as MMP-1 and MMP-9, at 24 months. By month 6, TLR ligands within subgingival plaques decreased. The abundance of pathogenic bacteria correlated with levels of virulence factors, proinflammatory cytokines, MMPs, and severity of clinical measures. Two distinct constellations of pathogenic bacteria were identified. Gingival sites were categorized into responders and non-responders per clinical symptoms and biomarkers. The regimen yielded more responder sites (70%) versus the control (47%), p = 0.0002914. The regimen reduced pathogenic bacteria, IL-1\u03b2, MMP1, and MMP-9, paralleling clinical reductions in periodontal disease.<\/jats:p>","DOI":"10.3390\/ijms262210823","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T14:55:15Z","timestamp":1762527315000},"page":"10823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Bacterial Networks and Relationship to Host Responses in Early Periodontitis Population over 24 Months"],"prefix":"10.3390","volume":"26","author":[{"given":"Aaron R.","family":"Biesbrock","sequence":"first","affiliation":[{"name":"Global Oral Care R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sancai","family":"Xie","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1100-9361","authenticated-orcid":false,"given":"Ping","family":"Hu","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl S.","family":"Tansky","sequence":"additional","affiliation":[{"name":"Global Baby, Feminine, Family Care Life Sciences, The Procter & Gamble Company, Cincinnati, OH 45224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-0948","authenticated-orcid":false,"given":"Xingtao","family":"Wei","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Ye","sequence":"additional","affiliation":[{"name":"Global Oral Care R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Circello","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7193-3866","authenticated-orcid":false,"given":"Avi","family":"Zini","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, Hebrew University and Hadassah, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7309-1121","authenticated-orcid":false,"given":"Guy","family":"Tobias","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, Hebrew University and Hadassah, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makio","family":"Tamura","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjana","family":"Parlov","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"B2","DOI":"10.1093\/eurheartj\/suq002","article-title":"European Workshop in Periodontal Health and Cardiovascular Disease","volume":"12","author":"Sanz","year":"2010","journal-title":"Eur. 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