{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:03:28Z","timestamp":1789473808881,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"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>\n                    Since the late 19th century, the relationship between oral infections and systemic health has been widely debated. Recent advances in microbiome research suggest that oral microbial imbalance\u2014dysbiosis\u2014can contribute to systemic inflammatory and metabolic disorders. We propose that the term \u201coral-systemic dysbiosis\u201d more accurately captures the complex interactions linking oral microbial disruption to systemic disease risk. This conceptual reframing moves beyond a purely infectious model toward a systems-based understanding of oral\u2013body health connections. Furthermore, we hypothesize that oral administration of Generally Recognized as Safe (GRAS)-grade probiotic\n                    <jats:italic>Streptococcus salivarius<\/jats:italic>\n                    , such as strain K12, may help restore oral eubiosis and potentially reduce systemic inflammatory burden. While the hypothesis that oral probiotic maintenance may reduce the risk of systemic disorders remains to be clinically verified, defining oral\u2013systemic dysbiosis provides a useful conceptual foundation for the exploration of integrated preventive strategies linking oral and general health.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2025.1685071","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T06:26:40Z","timestamp":1764656800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["From periodontal infection to oral\u2013systemic dysbiosis: re-framing the oral microbiome\u2019s role in systemic health and the prophylactic potential of Streptococcus salivarius probiotics"],"prefix":"10.3389","volume":"16","author":[{"given":"Francesco","family":"Di Pierro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Fornaini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Maria","family":"Palazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Bertuccioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Tagg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Zerbinati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref1","article-title":"Chapter 7: \"microbiology of endodontic disease\"","volume-title":"Ingle's endodontics","author":"Baumgartner","year":"2008"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1177\/0022034519846113","article-title":"Periodontal medicine: 100 years of progress","volume":"98","author":"Beck","year":"2019","journal-title":"J. Dent. Res."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.neurol.2022.12.010","article-title":"Oral and intestinal dysbiosis in Parkinson's disease","volume":"179","author":"Berthouzoz","year":"2023","journal-title":"Rev. Neurol. (Paris)"},{"key":"ref4","first-page":"461","article-title":"The principles involved in focal infection as related to systemic disease","volume":"70","author":"Billings","year":"1916","journal-title":"Dent. Regist."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.chom.2023.01.018","article-title":"Mother-to-infant microbiota transmission and infant microbiota development across multiple body sites","volume":"31","author":"Bogaert","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"S40","DOI":"10.1002\/JPER.20-0090","article-title":"Choosing the left fork: Steven Offenbacher and understanding maternal periodontal disease and adverse pregnancy outcomes","volume":"91","author":"Boggess","year":"2020","journal-title":"J. Periodontol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1016\/j.chom.2023.10.007","article-title":"Cross-regulation of antibody responses against the SARS-CoV-2 spike protein and commensal microbiota via molecular mimicry","volume":"31","author":"Bondareva","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1111\/j.1365-2672.2006.02837.x","article-title":"A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodor parameters","volume":"100","author":"Burton","year":"","journal-title":"J. Appl. Microbiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s12602-010-9045-4","article-title":"Extended safety data for the Oral cavity probiotic Streptococcus salivarius K12","volume":"2","author":"Burton","year":"2010","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1099\/jmm.0.056663-0","article-title":"Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial","volume":"62","author":"Burton","year":"2013","journal-title":"J. Med. Microbiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"3050","DOI":"10.1128\/AEM.72.4.3050-3053.2006","article-title":"Safety assessment of the oral cavity probiotic Streptococcus salivarius K12","volume":"72","author":"Burton","year":"","journal-title":"Appl. Environ. Microbiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1016\/s0140-6736(02)11676-x","article-title":"Focal infection","volume":"360","author":"Bynum","year":"2002","journal-title":"Lancet"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s10266-021-00636-x","article-title":"Evolution of endodontic medicine: a critical narrative review of the interrelationship between endodontics and systemic pathological conditions","volume":"109","author":"Cintra","year":"2021","journal-title":"Odontology"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"239","DOI":"10.4103\/jfmpc.jfmpc_725_19","article-title":"Evaluation of role of periodontal pathogens in endodontic periodontal diseases","volume":"9","author":"Das","year":"2020","journal-title":"J. Family Med. Prim. Care"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1517\/14712598.2013.758711","article-title":"Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and\/or tonsillitis caused by Streptococcus pyogenes in adults","volume":"13","author":"Di Pierro","year":"2013","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.3390\/microorganisms10101926","article-title":"Clinical effects of Streptococcus salivarius K12 in hospitalized COVID-19 patients: results of a preliminary study","volume":"10","author":"Di Pierro","year":"2022","journal-title":"Microorganisms"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"612","DOI":"10.14219\/jada.archive.1951.0112","article-title":"An evaluation of the effect of dental foci of infection on health","volume":"42","author":"Eastlick","year":"1951","journal-title":"J. Am. Dent. Assoc."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"4709","DOI":"10.1128\/JB.00566-12","article-title":"Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability","volume":"194","author":"Filkins","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1556\/1886.2018.00022","article-title":"Influence of probiotic culture supernatants on in vitro biofilm formation of staphylococci","volume":"8","author":"Frickmann","year":"2018","journal-title":"Eur. J. Microbiol. Immunol. (Bp)"},{"key":"ref21","first-page":"154","article-title":"Chronic oral infections and their relation to diseases in other parts","volume":"70","author":"Gilmer","year":"1916","journal-title":"Dent. Regist."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/prd.12385","article-title":"Periodontitis and rheumatoid arthritis: what have we learned about their connection and their treatment?","volume":"87","author":"Gonz\u00e1lez-Febles","year":"2021","journal-title":"Periodontology"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1177\/0022034518805739","article-title":"The oral microbiota is modified by systemic diseases","volume":"98","author":"Graves","year":"2019","journal-title":"J. Dent. Res."},{"key":"ref24","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0011-8532(22)03048-8","article-title":"Focal infection: are oral foci of infection related to systemic disease?","volume":"4","author":"Grossman","year":"1960","journal-title":"Dent. Clin. N. Am."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/mi.2016.108","article-title":"The respiratory tract microbiome and lung inflammation: a two-way street","volume":"10","author":"Huffnagle","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1136\/bmj.2.2065.215","article-title":"Oral sepsis as a cause of disease","volume":"2","author":"Hunter","year":"1900","journal-title":"BMJ"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"671813","DOI":"10.3389\/fmicb.2021.671813","article-title":"Profiling of oral microbiota and cytokines in COVID-19 patients","volume":"12","author":"Iebba","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/s41597-025-04619-3","article-title":"Complete genome and transcriptome datasets of Streptococcus salivarius strains from healthy Korean subjects","volume":"12","author":"Jang","year":"2025","journal-title":"Sci Data"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1177\/0890334415585078","article-title":"Metagenomic analysis of Milk of healthy and mastitis-suffering women","volume":"31","author":"Jim\u00e9nez","year":"2015","journal-title":"J. Hum. Lact."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1136\/gutjnl-2018-316661","article-title":"Patients with colorectal cancer have identical strains of Fusobacterium nucleatum in their colorectal cancer and oral cavity","volume":"68","author":"Komiya","year":"2019","journal-title":"Gut"},{"key":"ref31","doi-asserted-by":"publisher","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":"ref32","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1186\/s40168-022-01435-4","article-title":"Alterations of oral microbiota and impact on the gut microbiome in type 1 diabetes mellitus revealed by integrated multi-omic analyses","volume":"10","author":"Kunath","year":"2022","journal-title":"Microbiome"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2100203","DOI":"10.1080\/19490976.2022.2100203","article-title":"Effect of a bacteriocin-producing Streptococcus salivarius on the pathogen Fusobacterium nucleatum in a model of the human distal colon","volume":"14","author":"Lawrence","year":"2022","journal-title":"Gut Microbes"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e175916","DOI":"10.1172\/jci.insight.175916","article-title":"The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis","volume":"9","author":"Li","year":"2024","journal-title":"JCI Insight"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12903-021-01606-z","article-title":"Streptococcus salivarius inhibits immune activation by periodontal disease pathogens","volume":"21","author":"MacDonald","year":"2021","journal-title":"BMC Oral Health"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3390\/diseases13060176","article-title":"The role of targeted microbiota therapy in the prevention and management of puerperal mastitis","volume":"13","author":"Matera","year":"2025","journal-title":"Diseases"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/S0140-6736(02)01387-9","article-title":"The human mouth as a focus of infection","volume":"138","author":"Miller","year":"1891","journal-title":"Lancet"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1111\/jcpe.12534","article-title":"Clinical research activity in periodontal medicine: a systematic mapping of trial registers","volume":"43","author":"Monsarrat","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref39","first-page":"165","article-title":"Relationships between chronic oral infectious diseases and systemic diseases","volume":"39","author":"Okuda","year":"1998","journal-title":"Bull. Tokyo Dent. Coll."},{"key":"ref40","first-page":"641","article-title":"Fundamentals suggested by recent researches for diagnosis, prognosis, and treatment of dental focal infections","volume":"12","author":"Price","year":"1925","journal-title":"J. Am. Dent. Assoc."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1001\/jama.1940.02810010003001","article-title":"Focal infections and systemic disease: a critical appraisal","volume":"114","author":"Reimann","year":"1940","journal-title":"JAMA"},{"key":"ref42","first-page":"285","article-title":"Relation of dental infection and systemic disease","volume":"71","author":"Rosenow","year":"1917","journal-title":"Dent. Regist."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e47638","DOI":"10.15252\/embr.201847638","article-title":"Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt\/\u03b2-catenin modulator Annexin A1","volume":"20","author":"Rubinstein","year":"2019","journal-title":"EMBO Rep."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/s41579-020-0367-2","article-title":"Host-microbiota interactions in immune-mediated diseases","volume":"18","author":"Ruff","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1111\/iej.13079","article-title":"Endodontics and diabetes: association versus causation","volume":"52","author":"Segura-Egea","year":"2019","journal-title":"Int. Endod. J."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/s41467-025-56470-0","article-title":"Sucrose-preferring gut microbes prevent host obesity by producing exopolysaccharides","volume":"16","author":"Shimizu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"S104","DOI":"10.1086\/523331","article-title":"The safety of probiotics","volume":"46","author":"Snydman","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref48","first-page":"727","article-title":"Management of mastitis in breastfeeding women","volume":"78","author":"Spencer","year":"2008","journal-title":"Am. Fam. Physician"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1161155","DOI":"10.3389\/fmicb.2023.1161155","article-title":"Beneficial modulation of human health in the oral cavity and beyond using bacteriocin-like inhibitory substance-producing streptococcal probiotics","volume":"14","author":"Tagg","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-24-0872","article-title":"Oral pathobiont Streptococcus anginosus is enriched in the gut of stroke patients and predicts 2-year cardiovascular outcome","author":"Tonomura","year":"2025","journal-title":"Circ. J."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e83418","DOI":"10.1371\/journal.pone.0083418","article-title":"Comparative genomics analysis of streptococcus isolates from the human small intestine reveals their adaptation to a highly dynamic ecosystem","volume":"8","author":"Van den Bogert","year":"2013","journal-title":"PLoS One"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41522-023-00370-y","article-title":"Antimicrobial potential of known and novel probiotics on in vitro periodontitis biofilms","volume":"9","author":"Van Holm","year":"","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1219692","DOI":"10.3389\/fmicb.2023.1219692","article-title":"Probiotics for oral health: do they deliver what they promise?","volume":"14","author":"Van Holm","year":"","journal-title":"Front. Microbiol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"110940","DOI":"10.1016\/j.intimp.2023.110940","article-title":"Periodontal health status, Porphyromonas gingivalis and anti-cyclic citrullinated peptide antibodies among rheumatoid arthritis patients","volume":"124","author":"Wan Jiun","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1002\/cre2.269","article-title":"Inhibitory effect of Streptococcus salivarius K12 and M18 on halitosis in vitro","volume":"6","author":"Yoo","year":"2020","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.cell.2017.07.008","article-title":"Fusobacterium nucleatum promotes Chemoresistance to colorectal cancer by modulating autophagy","volume":"170","author":"Yu","year":"2017","journal-title":"Cell"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1038\/ismej.2011.212","article-title":"The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates","volume":"6","author":"Zoetendal","year":"2012","journal-title":"ISME J."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1685071\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T06:26:41Z","timestamp":1764656801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1685071\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":57,"alternative-id":["10.3389\/fmicb.2025.1685071"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1685071","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]},"article-number":"1685071"}}