{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:42:27Z","timestamp":1791196947491,"version":"4.1.0"},"reference-count":126,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"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. Microbiol."],"abstract":"<jats:p>Periodontitis is a dysbiosis-driven chronic inflammatory disease characterized by complex interactions among the subgingival microbiome, microbial metabolism, and host immune responses. Accumulating evidence indicates that disease progression is not solely determined by the enrichment of specific periodontal pathogens but is critically associated with ecological disruption and functional reprogramming of the subgingival microbial community. During the transition from periodontal health to disease, microbial metabolism shifts from carbohydrate utilization toward proteolysis and amino acid fermentation, resulting in altered production of short-chain fatty acids, polyamines, volatile sulfur compounds, hydrogen sulfide, and nitric oxide. These metabolic alterations contribute to inflammasome activation, immune dysregulation, osteoclastogenesis, and progressive periodontal tissue destruction. Beyond local pathology, periodontal microorganisms and their metabolites can disseminate through the oral\u2013systemic axis, thereby influencing the pathogenesis of multiple systemic disorders. Recent advances in multi-omics technologies have further revealed that metabolic reprogramming represents a critical mechanistic link connecting ecological dysbiosis with host inflammatory responses. Consequently, therapeutic strategies are evolving from conventional antimicrobial approaches toward precision microbiome-based interventions, including probiotics, postbiotics, bacteriophages, predatory bacteria, metabolic modulation, and oral microbiome transplantation. In this review, we integrate current evidence on microbial ecology, metabolism, and host interactions and propose the Ecological Dysbiosis\u2013Metabolic Reprogramming\u2013Host Crosstalk framework. This framework highlights metabolic reprogramming as the central bridge linking microbial dysbiosis to host inflammatory damage and provides a conceptual basis for the development of precision periodontal medicine.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1906205","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:29:31Z","timestamp":1786080571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The subgingival microbiome in periodontitis: from ecological dysbiosis and metabolic reprogramming to precision interventions"],"prefix":"10.3389","volume":"17","author":[{"given":"Ping","family":"Peng","sequence":"first","affiliation":[{"name":"Oral Department of Kunming Tongren Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingpeng","family":"Cai","sequence":"additional","affiliation":[{"name":"Oral Department of Kunming Tongren Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Oral Department of Kunming Tongren Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youcheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Oral Department of Kunming Tongren Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Kuang","sequence":"additional","affiliation":[{"name":"Oral Department of Kunming Tongren Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.3390\/dj14040203","article-title":"Probiotics and Ozonated olive oil to maintain Oral Eubiosis in stage I and II periodontitis patients: a randomized triple-blind clinical trial","volume":"14","author":"Abbinante","year":"2026","journal-title":"Dent. J."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1038\/ismej.2012.174","article-title":"The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation","volume":"7","author":"Abusleme","year":"2013","journal-title":"ISME J."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e0033624","DOI":"10.1128\/jb.00336-24","article-title":"Lipid a remodeling modulates outer membrane vesicle biogenesis by Porphyromonas gingivalis","volume":"207","author":"Alaei","year":"2025","journal-title":"J. Bacteriol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.3390\/jcm13133781","article-title":"Impact of periodontitis on endothelial risk dysfunction and oxidative stress improvement in patients with cardiovascular disease","volume":"13","author":"Angjelova","year":"2024","journal-title":"J. Clin. Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"815","DOI":"10.3390\/antibiotics14080815","article-title":"Effects of antiseptic formulations on Oral microbiota and related systemic diseases: a scoping review","volume":"14","author":"Angjelova","year":"2025","journal-title":"Antibiotics"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"4828","DOI":"10.1038\/srep04828","article-title":"Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota","volume":"4","author":"Arimatsu","year":"2014","journal-title":"Sci. Rep."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1177\/0022034514538283","article-title":"Filifactor alocis: The Newly Discovered Kid on the Block with Special Talents","volume":"93","author":"Aruni","year":"2014","journal-title":"J Dent Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"998","DOI":"10.4014\/jmb.2302.02002","article-title":"Anti-inflammatory efficacy of human-derived Streptococcus salivarius on Periodontopathogen-induced inflammation","volume":"33","author":"Baek","year":"2023","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1111\/jre.70055","article-title":"Multi-omics signatures of periodontitis and periodontal therapy on the Oral and gut microbiome","volume":"60","author":"Baima","year":"2025","journal-title":"J. Periodontal Res."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1902\/annals.2002.7.1.29","article-title":"Porphyromonas gingivalis lipopolysaccharide displays functionally diverse interactions with the innate host defense system","volume":"7","author":"Bainbridge","year":"2002","journal-title":"Ann. Periodontol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.tim.2016.12.012","article-title":"Ecology of the Oral microbiome: beyond Bacteria","volume":"25","author":"Baker","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/s41579-023-00963-6","article-title":"The oral microbiome: diversity, biogeography and human health","volume":"22","author":"Baker","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.3390\/ijms21061984","article-title":"Candida albicans shields the periodontal killer Porphyromonas gingivalis from recognition by the host immune system and supports the bacterial infection of gingival tissue","volume":"21","author":"Bartnicka","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1617015","DOI":"10.1080\/20002297.2019.1617015","article-title":"H2S mediates increased interleukin (IL)-1\u03b2 and IL-18 production in leukocytes from patients with periodontitis","volume":"11","author":"Basic","year":"2019","journal-title":"J. Oral Microbiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1186\/s12903-025-05888-5","article-title":"Clinical effects of probiotics on the treatment of gingivitis and periodontitis: a systematic review and meta-analysis","volume":"25","author":"Benavides-Reyes","year":"2025","journal-title":"BMC Oral Health"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.identj.2024.07.005","article-title":"Impact of mouthwash-induced Oral microbiome disruption on Alzheimer's disease risk: a perspective review","volume":"75","author":"Boulares","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"103768","DOI":"10.1016\/j.jdent.2021.103768","article-title":"Effects of chlorhexidine mouthwash on the oral microbiome","volume":"113","author":"Brookes","year":"2021","journal-title":"J. Dent."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.niox.2022.05.004","article-title":"The oral microbiome, nitric oxide and exercise performance","author":"Bryan","year":"2022","journal-title":"Nitric Oxide"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.bj.2018.12.001","article-title":"Association between periodontal pathogens and systemic disease","volume":"42","author":"Bui","year":"2019","journal-title":"Biom. J."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1902\/jop.2010.100080","article-title":"Oral malodorous compound causes oxidative stress and p53-mediated programmed cell death in keratinocyte stem cells","volume":"81","author":"Calenic","year":"2010","journal-title":"J. Periodontol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/jre.12022","article-title":"Association of subgingival colonization of Candida albicans and other yeasts with severity of chronic periodontitis","volume":"48","author":"Canabarro","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3390\/medicina56060272","article-title":"Periodontitis, low-grade inflammation and systemic health: a scoping review","volume":"56","author":"Cecoro","year":"2020","journal-title":"Medicina"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.bbrc.2009.11.113","article-title":"Bacteria-derived hydrogen sulfide promotes IL-8 production from epithelial cells","volume":"391","author":"Chen","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41522-016-0009-7","article-title":"Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients","volume":"2","author":"Chhibber-Goel","year":"2016","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1016\/j.chom.2021.09.009","article-title":"Episymbiotic Saccharibacteria suppresses gingival inflammation and bone loss in mice through host bacterial modulation","volume":"29","author":"Chipashvili","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3290\/j.qi.a34980","article-title":"Adverse pregnancy outcomes and periodontitis: a systematic review and meta-analysis exploring potential association","volume":"47","author":"Corbella","year":"2016","journal-title":"Quintessence Int."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e0138651","DOI":"10.1371\/journal.pone.0138651","article-title":"Isolation of a novel phage with activity against Streptococcus mutans biofilms","volume":"10","author":"Dalmasso","year":"2015","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/j.2041-1014.2010.00592.x","article-title":"Predation of oral pathogens by Bdellovibrio bacteriovorus 109J","volume":"26","author":"Dashiff","year":"2011","journal-title":"Mol Oral Microbiol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"5002","DOI":"10.1128\/JB.00542-10","article-title":"The human oral microbiome","volume":"192","author":"Dewhirst","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1177\/0022034519880157","article-title":"Microbial interactions in Oral communities mediate emergent biofilm properties","volume":"99","author":"Diaz","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"eaau3333","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer's disease brains: evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"Dominy","year":"2019","journal-title":"Sci. Adv."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1543030","DOI":"10.3389\/froh.2025.1543030","article-title":"Increased bacterial load of Filifactor alocis in deep periodontal pockets discriminate between periodontitis stage 3 and 4","volume":"6","author":"Faisal","year":"2025","journal-title":"Front. Oral Health"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1053\/j.ajkd.2007.09.018","article-title":"Periodontal disease and other nontraditional risk factors for CKD","volume":"51","author":"Fisher","year":"2008","journal-title":"Am. J. Kidney Dis."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1673512","DOI":"10.3389\/fcimb.2025.1673512","article-title":"Oral pathogens meet the gut microbiome: new mechanistic insights on systemic disease","volume":"15","author":"Gan","year":"2026","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","article-title":"Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the global burden of disease study 2017","volume":"392","year":"2018","journal-title":"Lancet"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1038\/ismej.2011.191","article-title":"Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing","volume":"6","author":"Griffen","year":"2012","journal-title":"ISME J."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1250263","DOI":"10.3389\/fcvm.2023.1250263","article-title":"Oral microbiome mediated inflammation, a potential inductor of vascular diseases: a comprehensive review","volume":"10","author":"Gualtero","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/omi.12322","article-title":"A double-edged sword: role of butyrate in the oral cavity and the gut","volume":"36","author":"Guan","year":"2021","journal-title":"Mol Oral Microbiol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1177\/23800844211039722","article-title":"Unusual findings in trials evaluating adjuncts to scaling and root Planing: Meta-analysis (part 1)","volume":"7","author":"Gunsolley","year":"2022","journal-title":"JDR Clin. Trans. Res."},{"key":"ref40","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":"ref41","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":"ref42","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3390\/dj10100195","article-title":"Calculus as a risk factor for periodontal disease: narrative review on treatment indications when the response to scaling and root Planing is inadequate","volume":"10","author":"Harrel","year":"2022","journal-title":"Dent. J."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1073\/pnas.1419038112","article-title":"Cultivation of a human-associated TM7 phylotype reveals a reduced genome and epibiotic parasitic lifestyle","volume":"112","author":"He","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1111\/prd.12008","article-title":"Surgical and nonsurgical periodontal therapy. Learned and unlearned concepts","volume":"62","author":"Heitz-Mayfield","year":"2013","journal-title":"Periodontol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1111\/iej.14164","article-title":"Endodontic treatment modifies circulatory inflammatory mediator levels: a systematic review with meta-analysis","volume":"58","author":"Jakovljevic","year":"2025","journal-title":"Int. Endod. J."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1080\/17460913.2025.2535901","article-title":"The effect of bacteriophage in oral health: developing microbial ecology and emerging potential therapeutic target","volume":"20","author":"Jalili","year":"2025","journal-title":"Future Microbiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1111\/jcpe.12542","article-title":"Stimulation of the nitrate-nitrite-NO-metabolism by repeated lettuce juice consumption decreases gingival inflammation in periodontal recall patients: a randomized, double-blinded, placebo-controlled clinical trial","volume":"43","author":"Jockel-Schneider","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"116","DOI":"10.4103\/amhs.amhs_191_25","article-title":"Precision periodontics: reimagining periodontal care through precision diagnostics and targeted therapies","volume":"14","author":"Joshi","year":"2026","journal-title":"Arch. Med. Health Sci."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"2469890","DOI":"10.1080\/20002297.2025.2469890","article-title":"Oral bacteriophages and their potential as adjunctive treatments for periodontitis: a narrative review","volume":"17","author":"Kabwe","year":"2025","journal-title":"J. Oral Microbiol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"e0016221","DOI":"10.1128\/mSphere.00162-21","article-title":"Dental plaque microbial resistomes of periodontal health and disease and their changes after scaling and root planing therapy","volume":"6","author":"Kang","year":"2021","journal-title":"mSphere"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/prd.12398","article-title":"Oral health's inextricable connection to systemic health: special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions","volume":"87","author":"Kapila","year":"2021","journal-title":"Periodontol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1177\/0022034514552491","article-title":"Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression","volume":"93","author":"Kassebaum","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/sj.bdj.2016.865","article-title":"The oral microbiome - an update for oral healthcare professionals","volume":"221","author":"Kilian","year":"2016","journal-title":"Br. Dent. J."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/nrmicro2381","article-title":"Oral multispecies biofilm development and the key role of cell-cell distance","volume":"8","author":"Kolenbrander","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/j.1399-302X.2005.00239.x","article-title":"Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity","volume":"20","author":"K\u00f5ll-Klais","year":"2005","journal-title":"Oral Microbiol. Immunol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"107612","DOI":"10.1016\/j.ijantimicag.2025.107612","article-title":"The prospect of approved and commercially available phage therapeutics","volume":"66","author":"K\u00f6nig","year":"2025","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.archoralbio.2016.09.008","article-title":"Changes in the oral ecosystem induced by the use of 8% arginine toothpaste","volume":"73","author":"Koopman","year":"2017","journal-title":"Arch. Oral Biol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1007\/s11926-014-0408-9","article-title":"The link between periodontal disease and rheumatoid arthritis: an updated review","volume":"16","author":"Koziel","year":"2014","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"828","DOI":"10.3390\/antibiotics14080828","article-title":"A comprehensive review of antibiotic resistance in the Oral microbiota: mechanisms, drivers, and emerging therapeutic strategies","volume":"14","author":"Kulis","year":"2025","journal-title":"Antibiotics"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1161\/01.ATV.0000082462.26258.FE","article-title":"Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice","volume":"23","author":"Lalla","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1186\/s12903-026-08003-4","article-title":"Oral probiotic Weissella cibaria improves halitosis and reduces periodontal pathogens: a randomized, double-blind, placebo-controlled trial","volume":"26","author":"Lee","year":"2026","journal-title":"BMC Oral Health"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"629723","DOI":"10.3389\/fcimb.2021.629723","article-title":"The Oral microbiome in periodontal health","volume":"11","author":"Lenartova","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"6176","DOI":"10.1073\/pnas.0308766101","article-title":"Methanogenic Archaea and human periodontal disease","volume":"101","author":"Lepp","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1556688","DOI":"10.3389\/fcimb.2025.1556688","article-title":"Innovative strategies targeting oral microbial dysbiosis: unraveling mechanisms and advancing therapies for periodontitis","volume":"15","author":"Li","year":"2025","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.1002\/jper.70141","article-title":"Consuming heat-inactivated Lactiplantibacillus pentosus ONRICb0240-containing postbiotics reduces gingival inflammation: a double-blind randomized clinical trial","author":"Liu","year":"2026","journal-title":"J. Periodontol."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1128\/iai.42.2.659-667.1983","article-title":"Relationship between oxygen tension and subgingival bacterial flora in untreated human periodontal pockets","volume":"42","author":"Loesche","year":"1983","journal-title":"Infect. Immun."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.anaerobe.2014.09.011","article-title":"Effect of Bdellovibrio bacteriovorus HD100 on multispecies oral communities","volume":"35","author":"Loozen","year":"2015","journal-title":"Anaerobe"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"282","DOI":"10.5051\/jpis.2103460173","article-title":"Subgingival microbiome in periodontitis and type 2 diabetes mellitus: an exploratory study using metagenomic sequencing","volume":"52","author":"Lu","year":"2022","journal-title":"J. Periodontal Implant Sci."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"1451683","DOI":"10.3389\/fcimb.2024.1451683","article-title":"Porphyromonas gingivalis triggers microglia activation and neurodegenerative processes through NOX4","volume":"14","author":"Magnusson","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1111\/jcpe.12545","article-title":"Clinical efficacy of probiotics as an adjunctive therapy to non-surgical periodontal treatment of chronic periodontitis: a systematic review and meta-analysis","volume":"43","author":"Martin-Cabezas","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"6775","DOI":"10.12998\/wjcc.v12.i35.6775","article-title":"Periodontitis and chronic kidney disease: a bidirectional relationship based on inflammation and oxidative stress","volume":"12","author":"Mart\u00ednez Nieto","year":"2024","journal-title":"World J. Clin. Cases"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1006\/anae.2001.0383","article-title":"Consumption of peptide-derived arginine by a periodontopathogenic bacterium, Porphyromonas gingivalis","volume":"7","author":"Masuda","year":"2001","journal-title":"Anaerobe"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/jop.70111","article-title":"Mind your mouth: impact of Oral Bacteria on Alzheimer's disease","volume":"55","author":"Mohammed","year":"2026","journal-title":"J. Oral Pathol. Med."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3390\/jof4040122","article-title":"Candida interactions with the oral bacterial microbiota","volume":"4","author":"Montelongo-Jauregui","year":"2018","journal-title":"J. Fungi"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"10883","DOI":"10.1038\/s41467-025-64608-3","article-title":"Considerations and perspectives on phage therapy from the transatlantic taskforce on antimicrobial resistance","volume":"16","author":"Moon","year":"2025","journal-title":"Nat. Commun."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.it.2017.08.005","article-title":"Tissue-specific immunity at the Oral mucosal barrier","volume":"39","author":"Moutsopoulos","year":"2018","journal-title":"Trends Immunol."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e0134234","DOI":"10.1371\/journal.pone.0134234","article-title":"Oral Administration of P. gingivalis induces Dysbiosis of gut microbiota and impaired barrier function leading to dissemination of Enterobacteria to the liver","volume":"10","author":"Nakajima","year":"2015","journal-title":"PLoS One"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/omi.12044","article-title":"The effect of arginine on oral biofilm communities","volume":"29","author":"Nascimento","year":"2014","journal-title":"Mol Oral Microbiol"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1016\/j.molmed.2023.08.006","article-title":"Microbiome-targeted interventions for the control of oral-gut dysbiosis and chronic systemic inflammation","volume":"29","author":"Pacheco-Yanes","year":"2023","journal-title":"Trends Mol. Med."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"S162","DOI":"10.1111\/jcpe.12946","article-title":"Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and Peri-implant diseases and conditions","author":"Papapanou","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/j.1600-051X.2007.01173.x","article-title":"A systematic review and meta-analyses on C-reactive protein in relation to periodontitis","volume":"35","author":"Paraskevas","year":"2008","journal-title":"J. Clin. Periodontol."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.imbio.2015.05.008","article-title":"Lipopolysaccharide of Aggregatibacter actinomycetemcomitans induces the expression of chemokines MCP-1, MIP-1\u03b1, and IP-10 via similar but distinct signaling pathways in murine macrophages","volume":"220","author":"Park","year":"2015","journal-title":"Immunobiology"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1186\/s12903-024-04770-0","article-title":"Nationwide exploration: assessing oral microbiome knowledge among dental professionals in Saudi Arabia and its implications for oral health care","volume":"24","author":"Parveen","year":"2024","journal-title":"BMC Oral Health"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"106475","DOI":"10.1016\/j.rmed.2021.106475","article-title":"The role of oral microbiome in respiratory health and diseases","volume":"185","author":"Pathak","year":"2021","journal-title":"Respir. Med."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.3390\/ma12122008","article-title":"Evaluation of predation capability of periodontopathogens bacteria by Bdellovibrio bacteriovorus HD100. An in vitro study","volume":"12","author":"Patini","year":"2019","journal-title":"Materials"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1177\/0022034514542468","article-title":"Newly identified pathogens associated with periodontitis: a systematic review","volume":"93","author":"P\u00e9rez-Chaparro","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1128\/JB.01631-09","article-title":"Central role of the early colonizer Veillonella sp. in establishing multispecies biofilm communities with initial, middle, and late colonizers of enamel","volume":"192","author":"Periasamy","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"665","DOI":"10.3233\/JAD-121918","article-title":"Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer's disease brain tissue","volume":"36","author":"Poole","year":"2013","journal-title":"J. Alzheimer's Dis"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s00125-011-2342-y","article-title":"Periodontitis and diabetes: a two-way relationship","volume":"55","author":"Preshaw","year":"2012","journal-title":"Diabetologia"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/prd.12433","article-title":"Periodontitis and cardiometabolic disorders: the role of lipopolysaccharide and endotoxemia","volume":"89","author":"Pussinen","year":"2022","journal-title":"Periodontol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12903-020-01127-1","article-title":"Antiseptics as adjuncts to scaling and root planing in the treatment of periodontitis: a systematic literature review","volume":"20","author":"Ramanauskaite","year":"2020","journal-title":"BMC Oral Health"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1902\/jop.2013.130142","article-title":"Antibiotic resistance in human chronic periodontitis microbiota","volume":"85","author":"Rams","year":"2014","journal-title":"J. Periodontol."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3389\/fcimb.2014.00124","article-title":"The impact of horizontal gene transfer on the adaptive ability of the human oral microbiome","volume":"4","author":"Roberts","year":"2014","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"12895","DOI":"10.1038\/s41598-020-69931-x","article-title":"Nitrate as a potential prebiotic for the oral microbiome","volume":"10","author":"Rosier","year":"2020","journal-title":"Sci. Rep."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"e0017022","DOI":"10.1128\/msystems.00170-22","article-title":"Fusobacterium nucleatum metabolically integrates commensals and pathogens in oral biofilms","volume":"7","author":"Sakanaka","year":"2022","journal-title":"mSystems"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1007\/s12223-025-01324-x","article-title":"Microbiota-based therapies in oral health and disorders","volume":"70","author":"Salah","year":"2025","journal-title":"Folia Microbiol."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The international scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/jcpe.13290","article-title":"Treatment of stage I-III periodontitis-the EFP S3 level clinical practice guideline","volume":"47","author":"Sanz","year":"2020","journal-title":"J. Clin. Periodontol."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/jcpe.13189","article-title":"Periodontitis and cardiovascular diseases: consensus report","volume":"47","author":"Sanz","year":"2020","journal-title":"J. Clin. Periodontol."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"e86708","DOI":"10.1371\/journal.pone.0086708","article-title":"The personal human oral microbiome obscures the effects of treatment on periodontal disease","volume":"9","author":"Schwarzberg","year":"2014","journal-title":"PLoS One"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"R42","DOI":"10.1186\/gb-2012-13-6-r42","article-title":"Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples","volume":"13","author":"Segata","year":"2012","journal-title":"Genome Biol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.2174\/1568026616666160930145649","article-title":"Phage therapy: a new horizon in the antibacterial treatment of Oral pathogens","volume":"17","author":"Shlezinger","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.3390\/biomedicines13071545","article-title":"Proteolytic activity inhibition in gingival fluid by cysteine protease inhibitors obtained from egg white and Fallopia japonica extract: an in vitro study","volume":"13","author":"Siewi\u0144ski","year":"2025","journal-title":"Biomedicine"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1111\/omi.12402","article-title":"Effects of Bdellovibrio bacteriovorus HD100 on experimental periodontitis in rats","volume":"38","author":"Silva","year":"2023","journal-title":"Mol Oral Microbiol"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/j.1600-051x.1998.tb02419.x","article-title":"Microbial complexes in subgingival plaque","volume":"25","author":"Socransky","year":"1998","journal-title":"J. Clin. Periodontol."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"372","DOI":"10.3390\/ijms23010372","article-title":"Pyroptosis-mediated periodontal disease","volume":"23","author":"Sordi","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"1797726","DOI":"10.3389\/fimmu.2026.1797726","article-title":"Host-pathogen interactions in periodontitis: an integrative interkingdom perspective","volume":"17","author":"Suarez","year":"2026","journal-title":"Front. Immunol."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1902\/jop.2010.100004","article-title":"Gram-negative periodontal bacteria induce the activation of toll-like receptors 2 and 4, and cytokine production in human periodontal ligament cells","volume":"81","author":"Sun","year":"2010","journal-title":"J. Periodontol."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"26291","DOI":"10.1038\/s41598-024-77909-2","article-title":"Autophagy mediates the impact of Porphyromonas gingivalis on short-chain fatty acids metabolism in periodontitis-induced gut dysbiosis","volume":"14","author":"Sun","year":"2024","journal-title":"Sci. Rep."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1177\/0022034515606045","article-title":"Oral microbiome metabolism: from \"who are they?\" to \"what are they doing?\"","volume":"94","author":"Takahashi","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1177\/0022034510377792","article-title":"Metabolomics of supragingival plaque and oral bacteria","volume":"89","author":"Takahashi","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"1716188","DOI":"10.3389\/froh.2026.1716188","article-title":"Novel small molecule targeting PgQC reduces Porphyromonas gingivalis virulence","volume":"7","author":"Taudte","year":"2026","journal-title":"Front. Oral Health"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"4845","DOI":"10.2147\/JIR.S460954","article-title":"CORM-3 inhibits the inflammatory response of human periodontal ligament fibroblasts stimulated by LPS and high glucose","volume":"17","author":"Tian","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1177\/0022034512449465","article-title":"Probiotics for caries prevention and control","volume":"24","author":"Twetman","year":"2012","journal-title":"Adv. Dent. Res."},{"key":"ref115","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1177\/0022034508329693","article-title":"Bdellovibrio bacteriovorus attacks Aggregatibacter actinomycetemcomitans","volume":"88","author":"Van Essche","year":"2009","journal-title":"J. Dent. Res."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.phrs.2012.11.006","article-title":"The oral microbiome in health and disease","volume":"69","author":"Wade","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1128\/AEM.71.1.354-362.2005","article-title":"Interactions between oral bacteria: inhibition of Streptococcus mutans bacteriocin production by Streptococcus gordonii","volume":"71","author":"Wang","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.3389\/fimmu.2020.01487","article-title":"AIM2 Inflammasome's first decade of discovery: focus on Oral diseases","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"4673","DOI":"10.3390\/ijms20194673","article-title":"Postbiotics and their potential applications in early life nutrition and beyond","volume":"20","author":"Wegh","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref120","doi-asserted-by":"publisher","first-page":"102325","DOI":"10.1016\/j.xcrm.2025.102325","article-title":"Oral virome metagenomic catalog links Porphyromonas gingivalis phages to obesity and type 2 diabetes","volume":"6","author":"Xu","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"953277","DOI":"10.3389\/fcimb.2022.953277","article-title":"Pyroptosis in periodontitis: from the intricate interaction with apoptosis, NETosis, and necroptosis to the therapeutic prospects","volume":"12","author":"Xu","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/bs.apcsb.2019.12.001","article-title":"Roles of Porphyromonas gingivalis and its virulence factors in periodontitis","volume":"120","author":"Xu","year":"2020","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1177\/00220345231181539","article-title":"Endothelial insulin resistance exacerbates experimental periodontitis","volume":"102","author":"Zeze","year":"2023","journal-title":"J. Dent. Res."},{"key":"ref124","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.jds.2024.09.021","article-title":"Polyinosinic-polycytidylic acid modulates Porphyromonas gingivalis-induced cell apoptosis via the janus kinase\/ signal transducer and activator of transcription signaling pathway","volume":"20","author":"Zhang","year":"2025","journal-title":"J. Dent. Sci."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"1643691","DOI":"10.3389\/fmicb.2025.1643691","article-title":"Akkermansia muciniphila regulates the gut microenvironment and alleviate periodontal inflammmation in mice with periodontitis","volume":"16","author":"Zhang","year":"2025","journal-title":"Front. Microbiol."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1080\/17425247.2021.1908260","article-title":"Treatment challenges and delivery systems in immunomodulation and probiotic therapies for periodontitis","volume":"18","author":"Zidar","year":"2021","journal-title":"Expert Opin. Drug Deliv."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1906205\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:29:33Z","timestamp":1786080573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1906205\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":126,"alternative-id":["10.3389\/fmicb.2026.1906205"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1906205","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"article-number":"1906205"}}