{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:46:06Z","timestamp":1793155566994,"version":"4.5.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Periodontitis and peri-implantitis are chronic inflammatory diseases which are primarily driven by excessive and dysregulated immune responses. This would result in irreversible tissue destruction around teeth and implants. Although the microbiome serves as an initiator of inflammation and leads to microbial dysbiosis, persistent and unresolved inflammation is the primary driver of tissue and bone loss. These conditions result from a dynamic interplay between the host immune response and pathogenic biofilms. Microbial dysbiosis results from a shift from a eubiotic (symbiotic) oral microbiome to a dysbiotic microbial community. This is initiated by excessive inflammation and manipulates host immunity to promote chronic inflammation. Concurrently, immune dysregulation, including imbalances in innate and adaptive immune responses that result from a failure of resolution of inflammation pathways, exacerbates tissue destruction through the overproduction of pro-inflammatory cytokines and the activation of destructive pathways, such as neutrophil-mediated degradation and osteoclast activation. This review explores the mechanisms underlying microbial dysbiosis and immune dysregulation in periodontitis and peri-implantitis, emphasizing their contribution to inflammation, bone resorption, and disease progression.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1678163","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:54:25Z","timestamp":1767768865000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Microbial dysbiosis and immune dysregulation in periodontitis and peri-implantitis"],"prefix":"10.3389","volume":"15","author":[{"given":"Nika","family":"Mehrnia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E","family":"Van Dyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1056914","article-title":"Osteoimmune regulation underlies oral implant osseointegration and its perturbation","volume":"13","author":"Albrektsson","year":"2022","journal-title":"Front. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"19018","DOI":"10.1038\/s41598-020-76038-w","article-title":"Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis","volume":"10","author":"Alvarez","year":"2020","journal-title":"Sci. Rep."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/259074","article-title":"Relationship between periodontitis and rheumatoid arthritis: review of the literature","volume":"2015","author":"Ara\u00fajo","year":"2015","journal-title":"Mediators Inflamm."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/jre.70040","article-title":"Inflammatory and immunological basis of periodontal diseases","author":"Baima","year":"2025","journal-title":"J. Periodontal Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/jcpe.13046","article-title":"An appraisal of the role of specific bacteria in the initial pathogenesis of periodontitis","volume":"46","author":"Bartold","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nri.2015.4","article-title":"Specialized pro-resolving mediators: endogenous regulators of infection and inflammation","volume":"16","author":"Basil","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015370","article-title":"Neutrophils\u2019 Contribution to periodontitis and periodontitis-associated cardiovascular diseases","volume":"24","author":"Bassani","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1177\/154405910708600409","article-title":"MMPs, IL-1, and TNF are regulated by IL-17 in periodontitis","volume":"86","author":"Beklen","year":"2007","journal-title":"J. Dent. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1186\/s12903-021-01665-2","article-title":"Evaluation of biofilm colonization on multi-part dental implants in a rat model","volume":"21","author":"Blank","year":"2021","journal-title":"BMC Oral. Health"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1111\/clr.14153","article-title":"Microbiota associated with peri-implantitis-A systematic review with meta-analyses","volume":"34","author":"Carvalho","year":"2023","journal-title":"Clin. Oral. Implants Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/prd.12002","article-title":"Inflammatory and immune pathways in the pathogenesis of periodontal disease","volume":"64","author":"Cekici","year":"2014","journal-title":"Periodontol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2021.1979882","article-title":"Pathobionts: mechanisms of survival, expansion, and interaction with host with a focus on Clostridioides difficile","volume":"13","author":"Chandra","year":"2021","journal-title":"Gut Microbes"},{"key":"B13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41368-023-00256-x","article-title":"Titanium particles in peri-implantitis: distribution, pathogenesis and prospects","volume":"15","author":"Chen","year":"2023","journal-title":"Int. J. Oral. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/mp.2014.146","article-title":"Developmental endothelial locus-1 is a homeostatic factor in the central nervous system limiting neuroinflammation and demyelination","volume":"20","author":"Choi","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.coi.2019.02.002","article-title":"Studying interactions between dendritic cells and T cells in vivo","volume":"58","author":"Chudnovskiy","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1111\/omi.12165","article-title":"Global TLR2 and 4 deficiency in mice impacts bone resorption, inflammatory markers and atherosclerosis to polymicrobial infection","volume":"32","author":"Chukkapalli","year":"2017","journal-title":"Mol. Oral. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/prd.12296","article-title":"The role of the microbiota in periodontal disease","volume":"83","author":"Curtis","year":"2020","journal-title":"Periodontol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1186\/s12903-022-02493-8","article-title":"What is the prevalence of peri-implantitis? A systematic review and meta-analysis","volume":"22","author":"Diaz","year":"2022","journal-title":"BMC Oral. Health"},{"key":"B19","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.adaj.2018.04.023","article-title":"Periodontitis in US adults: national health and nutrition examination survey 2009-2014","volume":"149","author":"Eke","year":"2018","journal-title":"J. Am. Dent. Assoc."},{"key":"B20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/j.1600-0765.2012.01500.x","article-title":"Comparison of CCL28, interleukin-8, interleukin-1\u03b2 and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis","volume":"48","author":"Ertugrul","year":"2013","journal-title":"J. Periodontal Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e126155","DOI":"10.1172\/JCI126155","article-title":"Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation","volume":"132","author":"Failer","year":"2022","journal-title":"J. Clin. Invest."},{"key":"B22","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41522-020-00155-7","article-title":"Strong oral plaque microbiome signatures for dental implant diseases identified by strain-resolution metagenomics","volume":"6","author":"Ghensi","year":"2020","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1007\/s00784-020-03435-w","article-title":"Treg and TH17 link to immune response in individuals with peri-implantitis: a preliminary report","volume":"25","author":"Giro","year":"2021","journal-title":"Clin. Oral. Investig."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.it.2013.09.001","article-title":"Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response","volume":"35","author":"Hajishengallis","year":"2014","journal-title":"Trends Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/nri3785","article-title":"Periodontitis: from microbial immune subversion to systemic inflammation","volume":"15","author":"Hajishengallis","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.molmed.2019.02.010","article-title":"DEL-1-regulated immune plasticity and inflammatory disorders","volume":"25","author":"Hajishengallis","year":"2019","journal-title":"Trends Mol. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/nrmicro2873","article-title":"The keystone-pathogen hypothesis","volume":"10","author":"Hajishengallis","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1111\/j.2041-1014.2012.00663.x","article-title":"Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology","volume":"27","author":"Hajishengallis","year":"2012","journal-title":"Mol. Oral. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/prd.12371","article-title":"Polymicrobial communities in periodontal disease: Their quasi-organismal nature and dialogue with the host","volume":"86","author":"Hajishengallis","year":"2021","journal-title":"Periodontol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"7021","DOI":"10.4049\/jimmunol.179.10.7021","article-title":"Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo1","volume":"179","author":"Hasturk","year":"2007","journal-title":"J. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1096\/fj.05-4724fje","article-title":"RvE1 protects from local inflammation and osteoclastmediated bone destruction in periodontitis","volume":"20","author":"Hasturk","year":"2006","journal-title":"FASEB J."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.704163","article-title":"Safety and preliminary efficacy of a novel host-modulatory therapy for reducing gingival inflammation","volume":"12","author":"Hasturk","year":"2021","journal-title":"Front. Immunol."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1466417","article-title":"Role of immune dysregulation in peri-implantitis","volume":"15","author":"Huang","year":"2024","journal-title":"Front. Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1590\/1678-775720160082","article-title":"Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease","volume":"24","author":"Kampits","year":"2016","journal-title":"J. Appl. Oral. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/jopr.13270","article-title":"Microbiological profile and human immune response associated with peri-implantitis: A systematic review","volume":"30","author":"Kensara","year":"2021","journal-title":"J. Prosthodont."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00053","article-title":"Oral biofilms from symbiotic to pathogenic interactions and associated disease \u2013connection of periodontitis and rheumatic arthritis by peptidylarginine deiminase","volume":"9","author":"Kriebel","year":"2018","journal-title":"Front. Microbiol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.691216","article-title":"Subgingival microbiome and specialized pro-resolving lipid mediator pathway profiles are correlated in periodontal inflammation","volume":"12","author":"Lee","year":"2021","journal-title":"Front. Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.4049\/jimmunol.1600859","article-title":"Resolvin E1 reverses experimental periodontitis and dysbiosis","volume":"197","author":"Lee","year":"2016","journal-title":"J. Immunol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1111\/clr.14120","article-title":"Mucosal bleeding correlates with submucosal microbial dysbiosis in peri-implant mucositis of patients with periodontitis","volume":"34","author":"Li","year":"2023","journal-title":"Clin. Oral. Implants Res."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12395","article-title":"IL-17 regulates the expressions of RANKL and OPG in human periodontal ligament cells via TRAF6\/TBK1-JNK\/NF-\u03baB pathways","author":"Lin","year":"2014","journal-title":"Immunology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1902\/jop.1965.36.3.177","article-title":"Experimental gingivitis in man","volume":"36","author":"L\u00f6e","year":"1965","journal-title":"J. Periodontol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/prd.12297","article-title":"The role of inflammation and genetics in periodontal disease","volume":"83","author":"Loos","year":"2020","journal-title":"Periodontol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"8272","DOI":"10.1038\/ncomms9272","article-title":"Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3\u03b2-C\/EBP\u03b2 pathway","volume":"6","author":"Maekawa","year":"2015","journal-title":"Nat. Commun."},{"key":"B44","unstructured":"Figure\u00a01. Cycle of inflammation in periodontal and peri implant tissues\n          \n          \n            \n              Mehrnia\n              N.\n            \n          \n          \n          2025"},{"key":"B45","unstructured":"Figure\u00a02.Immune Response across periodontal lesion stages\n          \n          \n            \n              Mehrnia\n              N.\n            \n          \n          \n          2025"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e00462","DOI":"10.1128\/AEM.00462-17","article-title":"Signature of microbial dysbiosis in periodontitis","volume":"83","author":"Meuric","year":"2017","journal-title":"Appl. Environ. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.3390\/genes16111308","article-title":"Genetic testing in periodontitis: A narrative review on current applications, limitations, and future perspectives","volume":"16","author":"Modafferi","year":"2025","journal-title":"Genes"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/jre.12479","article-title":"Can degradation products released from dental implants affect peri-implant tissues","volume":"53","author":"Noronha Oliveira","year":"2018","journal-title":"J. Periodontal Res."},{"key":"B49","first-page":"235","article-title":"Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab. Investig","volume":"34","author":"Page","year":"1976","journal-title":"J. Tech. Methods Pathol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41368-019-0064-z","article-title":"The cytokine network involved in the host immune response to periodontitis","volume":"11","author":"Pan","year":"2019","journal-title":"Int. J. Oral. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41368-019-0064-z","article-title":"The cytokine network involved in the host immune response to periodontitis","volume":"11","author":"Pan","year":"2019","journal-title":"Int. J. Oral. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41415-019-0794-5","article-title":"Periodontitis and diabetes","volume":"227","author":"Preshaw","year":"2019","journal-title":"Br. Dent. J."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/jre.70002","article-title":"Genetic susceptibility to periodontitis","author":"Richter","year":"2025","journal-title":"J. Periodontal Res"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8050661","article-title":"The microbiome of peri-implantitis: A systematic review and meta-analysis","volume":"8","author":"Sahrmann","year":"2020","journal-title":"Microorganisms"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1111\/jcpe.14193","article-title":"Genetic loci associated with periodontitis: the finnGen study based on national health registers","volume":"52","author":"Salminen","year":"2025","journal-title":"J. Clin. Periodontol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1002\/JPER.21-0120","article-title":"Dysbiosis revisited: Understanding the role of the oral microbiome in the pathogenesis of gingivitis and periodontitis: A critical assessment","volume":"92","author":"Scannapieco","year":"2021","journal-title":"J. Periodontol."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.766944","article-title":"Periodontal disease: the good, the bad, and the unknown","volume":"11","author":"Sedghi","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nri2294","article-title":"Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators","volume":"8","author":"Serhan","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105540","article-title":"Osteoimmunology in periodontitis: local proteins and compounds to alleviate periodontitis","volume":"23","author":"Sirisereephap","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1111\/odi.12468","article-title":"The role of Toll-like receptors in periodontitis","volume":"23","author":"Song","year":"2017","journal-title":"Oral. Dis."},{"key":"B61","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mam.2017.04.006","article-title":"Pro-resolving mediators in the regulation of periodontal disease","volume":"58","author":"Van Dyke","year":"2017","journal-title":"Mol. Aspects Med."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13424","article-title":"Periodontitis: microbial dysbiosis, non-resolving inflammation, or both","author":"Van Dyke","year":"2025","journal-title":"J. Periodontal Res"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00511","article-title":"The nexus between periodontal inflammation and dysbiosis","volume":"11","author":"Van Dyke","year":"2020","journal-title":"Front. Immunol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1177\/154405910308200202","article-title":"Resolution of inflammation: A new paradigm for the pathogenesis of periodontal diseases","volume":"82","author":"Van Dyke","year":"2003","journal-title":"J. Dent. Res."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.670178","article-title":"Metabolic disturbance and th17\/treg imbalance are associated with progression of gingivitis","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2838","DOI":"10.1111\/odi.14782","article-title":"Microbiome-based therapies for periodontitis and peri-implantitis","volume":"30","author":"Wei","year":"2024","journal-title":"Oral. Dis."},{"key":"B67","doi-asserted-by":"publisher","first-page":"4151","DOI":"10.1128\/IAI.00600-10","article-title":"Impaired immune tolerance to Porphyromonas gingivalis lipopolysaccharide promotes neutrophil migration and decreased apoptosis","volume":"78","author":"Zaric","year":"2010","journal-title":"Infect. Immun."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1053175","article-title":"Developmental endothelial locus-1 in cardiovascular and metabolic diseases: A promising biomarker and therapeutic target","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1678163\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:54:27Z","timestamp":1767768867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1678163\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":68,"alternative-id":["10.3389\/fcimb.2025.1678163"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1678163","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"article-number":"1678163"}}