{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:14:30Z","timestamp":1788372870637,"version":"build-2803163510"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Although established periodontal pathobionts are frequently detected, their presence alone does not fully explain variations in disease severity, highlighting the need to identify additional microbial contributors. This systematic review evaluates the available evidence on the association between\n                      <jats:italic>Eubacterium saphenum<\/jats:italic>\n                      and the severity of periodontitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The review was conducted in accordance with the PRISMA 2020 framework and registered in PROSPERO (CRD420251273182). Observational studies involving systemically healthy adults were included that compared individuals with periodontitis and periodontal health, reporting detection and\/or relative abundance of\n                      <jats:italic>E. saphenum<\/jats:italic>\n                      in saliva and\/or subgingival biofilm samples. Study quality was appraised using the AXIS tool, and certainty of evidence was assessed using the GRADE framework.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight observational studies (304 healthy controls vs. 510 periodontitis cases) from Asia, Europe, and the Americas met the inclusion criteria. Across multiple detection platforms,\n                      <jats:italic>E. saphenum<\/jats:italic>\n                      showed a qualitatively similar direction of association, being more frequently detected and\/or present at higher relative abundance in periodontitis than in periodontal health controls. Among studies applying the 2018 periodontal classification system and reporting stage-specific analyses, higher detection or enrichment of\n                      <jats:italic>E. saphenum<\/jats:italic>\n                      was generally observed in advanced disease (stages III-IV). The certainty of evidence was rated as low owing to the observational and predominantly cross-sectional design of the evidence, methodological heterogeneity, and lack of temporality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Low-certainty evidence suggests a positive directional association between\n                      <jats:italic>E. saphenum<\/jats:italic>\n                      and periodontitis, particularly in advanced Stage III\u2013IV disease. However, longitudinal, interventional, and mechanistic studies are required to clarify temporality and determine whether\n                      <jats:italic>E. saphenum<\/jats:italic>\n                      contributes functionally to periodontal dysbiosis or primarily represents a marker of established disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0357110","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:28:32Z","timestamp":1788370112000},"page":"e0357110","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between Eubacterium saphenum and periodontitis: A systematic review"],"prefix":"10.1371","volume":"21","author":[{"given":"Sarah","family":"Al-Rihaymee","sequence":"first","affiliation":[{"name":"Universiti Malaya","place":["Kuala Lumpur, Malaysia"],"department":["Department of Restorative Dentistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayder Raad","family":"Abdulbaqi","sequence":"additional","affiliation":[{"name":"University of Baghdad","place":["Baghdad, Iraq"],"department":["Department of Periodontics, College of Dentistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Abdulkareem","sequence":"additional","affiliation":[{"name":"University of Baghdad","place":["Baghdad, Iraq"],"department":["Department of Periodontics, College of Dentistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Himratul Aznita Wan","family":"Harun","sequence":"additional","affiliation":[{"name":"Universiti Malaya","place":["Kuala Lumpur, Malaysia"],"department":["Department of Oral and Craniofacial Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6824-3744","authenticated-orcid":true,"given":"Nor Adinar","family":"Baharuddin","sequence":"additional","affiliation":[{"name":"Universiti Malaya","place":["Kuala Lumpur, Malaysia"],"department":["Department of Restorative Dentistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"pone.0357110.ref001","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","author":"MS Tonetti","year":"2018","journal-title":"J Periodontol"},{"issue":"1","key":"pone.0357110.ref002","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/prd.12331","article-title":"Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy","volume":"84","author":"G Hajishengallis","year":"2020","journal-title":"Periodontol 2000"},{"key":"pone.0357110.ref003","doi-asserted-by":"crossref","first-page":"879131","DOI":"10.3389\/fdmed.2022.879131","article-title":"Modulating the immune response in periodontitis","volume":"3","author":"B Bezerra","year":"2022","journal-title":"Front Dent Med"},{"issue":"1","key":"pone.0357110.ref004","first-page":"20","article-title":"Developments in Research on the Relationship Between Porphyromonas gingivalis and Non-Oral Diseases","volume":"54","author":"K-K Zhang","year":"2023","journal-title":"J Sichuan Univ (Med Sci)"},{"key":"pone.0357110.ref005","first-page":"125","article-title":"No association between A actinomycetemcomitans or P gingivalis and chronic or aggressive periodontitis diagnosis","author":"L Nibali","journal-title":"Br Dent J"},{"issue":"2","key":"pone.0357110.ref006","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1600-051X.1998.tb02419.x","article-title":"Microbial complexes in subgingival plaque","volume":"25","author":"SS Socransky","year":"1998","journal-title":"J Clin Periodontol"},{"issue":"6","key":"pone.0357110.ref007","doi-asserted-by":"crossref","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":"G Hajishengallis","year":"2012","journal-title":"Mol Oral Microbiol"},{"issue":"8","key":"pone.0357110.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0136646","article-title":"Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola \/ Prevotella intermedia Co-Infection Are Associated with Severe Periodontitis in a Thai Population","volume":"10","author":"K Torrungruang","year":"2015","journal-title":"PLoS One"},{"issue":"7","key":"pone.0357110.ref009","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.micinf.2015.03.011","article-title":"Filifactor alocis--a 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Bacteriol"},{"key":"pone.0357110.ref013","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jecm.2010.12.008","article-title":"Significance of asaccharolytic eubacterium and closely related bacterial species in the human oral cavity","volume":"3","author":"F Nakazawa","year":"2011","journal-title":"J Exp Clin Med"},{"issue":"6","key":"pone.0357110.ref014","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/(SICI)1234-987X(199611)9:6<367::AID-MEH448>3.3.CO;2-C","article-title":"The Role ofEubacteriumSpecies in Periodontal Disease and Other Oral Infections","volume":"9","author":"WG Wade","year":"1996","journal-title":"Microb Ecol Health Dis"},{"issue":"8","key":"pone.0357110.ref015","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1128\/JCM.43.8.3944-3955.2005","article-title":"Identification of candidate periodontal pathogens and beneficial species by quantitative 16S clonal analysis","volume":"43","author":"PS Kumar","year":"2005","journal-title":"J Clin Microbiol"},{"key":"pone.0357110.ref016","doi-asserted-by":"crossref","first-page":"105758","DOI":"10.1016\/j.archoralbio.2023.105758","article-title":"Design and validation of a quantitative polymerase chain reaction test for the identification and quantification of uncultivable bacteria associated with periodontitis","volume":"154","author":"Y Castillo","year":"2023","journal-title":"Arch Oral Biol"},{"issue":"8","key":"pone.0357110.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0273523","article-title":"Differences in the subgingival microbiome according to stage of periodontitis: A comparison of two geographic regions","volume":"17","author":"GI Lafaurie","year":"2022","journal-title":"PLoS One"},{"issue":"6","key":"pone.0357110.ref018","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1007\/s00784-023-04907-5","article-title":"Differential analysis of culturable and unculturable subgingival target microorganisms according to the stages of periodontitis","volume":"27","author":"GI Lafaurie","year":"2023","journal-title":"Clin Oral Investig"},{"key":"pone.0357110.ref019","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"MJ Page","year":"2021","journal-title":"BMJ"},{"issue":"1","key":"pone.0357110.ref020","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s13643-017-0644-y","article-title":"Optimal database combinations for literature searches in systematic reviews: a prospective exploratory study","volume":"6","author":"WM Bramer","year":"2017","journal-title":"Syst Rev"},{"issue":"12","key":"pone.0357110.ref021","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-011458","article-title":"Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS)","volume":"6","author":"MJ Downes","year":"2016","journal-title":"BMJ 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Rating up the quality of evidence","volume":"64","author":"GH Guyatt","year":"2011","journal-title":"J Clin Epidemiol"},{"issue":"1","key":"pone.0357110.ref025","doi-asserted-by":"crossref","first-page":"100591","DOI":"10.1016\/j.job.2024.100591","article-title":"Oral microbiome profiles of gingivitis and periodontitis by next-generation sequencing among a group of hospital patients in Korea: A cross-sectional study","volume":"67","author":"Y-H Lee","year":"2025","journal-title":"J Oral Biosci"},{"key":"pone.0357110.ref026","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3389\/fcimb.2019.00216","article-title":"Identification of Salivary Microbiota and Its Association With Host Inflammatory Mediators in Periodontitis","volume":"9","author":"A Lundmark","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0357110.ref027","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.micpath.2015.09.009","article-title":"Periodontal-disease-associated biofilm: A reservoir for pathogens of medical importance","volume":"94","author":"AP Vieira Colombo","year":"2016","journal-title":"Microb Pathog"},{"key":"pone.0357110.ref028","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.archoralbio.2019.02.012","article-title":"Subgingival microbiome in Chinese patients with generalized aggressive periodontitis compared to healthy controls","volume":"101","author":"X Cui","year":"2019","journal-title":"Arch Oral Biol"},{"issue":"10","key":"pone.0357110.ref029","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1177\/0022034515594779","article-title":"Association of Synergistetes and Cyclodipeptides with Periodontitis","volume":"94","author":"JT Marchesan","year":"2015","journal-title":"J Dent Res"},{"issue":"1","key":"pone.0357110.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","article-title":"Development of a classification system for periodontal diseases and conditions","volume":"4","author":"GC Armitage","year":"1999","journal-title":"Ann Periodontol"},{"key":"pone.0357110.ref031","article-title":"A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification","author":"JG Caton","year":"2018","journal-title":"J Clin Periodontol"},{"key":"pone.0357110.ref032","doi-asserted-by":"crossref","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","volume":"45","author":"PN Papapanou","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"9","key":"pone.0357110.ref033","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.archoralbio.2011.02.009","article-title":"Association of red complex, A. actinomycetemcomitans and non-oral bacteria with periodontal diseases","volume":"56","author":"CM da Silva-Boghossian","year":"2011","journal-title":"Arch Oral Biol"},{"issue":"10","key":"pone.0357110.ref034","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1902\/jop.2007.060465","article-title":"Periodontal disease at the biofilm-gingival interface","volume":"78","author":"S Offenbacher","year":"2007","journal-title":"J Periodontol"},{"key":"pone.0357110.ref035","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1902\/annals.1999.4.1.53","article-title":"Consensus report: Aggressive periodontitis","volume":"4","author":"N Lang","year":"1999","journal-title":"Ann Periodontol"},{"issue":"2","key":"pone.0357110.ref036","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1620\/tjem.219.79","article-title":"Bactericidal activity in filtrated supernatant of Streptococcus sanguinis against multidrug-resistant Pseudomonas aeruginosa","volume":"219","author":"K Watanabe","year":"2009","journal-title":"Tohoku J Exp Med"},{"issue":"11","key":"pone.0357110.ref037","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1111\/jcpe.70017","article-title":"Saliva Versus All-Site Microbiome and Proteome Mapping in Periodontitis","volume":"52","author":"K Bao","year":"2025","journal-title":"J Clin Periodontol"},{"issue":"5","key":"pone.0357110.ref038","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/JPER.17-0377","article-title":"Influence of periodontal treatment on subgingival and salivary microbiotas","volume":"89","author":"D Belstr\u00f8m","year":"2018","journal-title":"J Periodontol"},{"issue":"12","key":"pone.0357110.ref039","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1099\/0022-1317-51-12-1090","article-title":"Comparison of 16S rDNA-based PCR and checkerboard DNA-DNA hybridisation for detection of selected endodontic pathogens","volume":"51","author":"JF Siqueira","year":"2002","journal-title":"J Med Microbiol"},{"issue":"20","key":"pone.0357110.ref040","doi-asserted-by":"crossref","first-page":"10172","DOI":"10.3390\/ijms262010172","article-title":"Measuring the Invisible: Microbial Diagnostics for Periodontitis-A Narrative Review","volume":"26","author":"M Usui","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0357110.ref041","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/prd.12571","article-title":"Microbial diagnostics in periodontal diseases","volume":"95","author":"D Manoil","year":"2024","journal-title":"Periodontol 2000"},{"issue":"12","key":"pone.0357110.ref042","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/jcpe.12470","article-title":"Relationship between periodontitis-associated subgingival microbiota and clinical inflammation by 16S pyrosequencing","volume":"42","author":"A Camelo-Castillo","year":"2015","journal-title":"J Clin Periodontol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0357110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:28:38Z","timestamp":1788370118000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0357110"}},"subtitle":[],"editor":[{"given":"Antonio","family":"Magan-Fernandez","sequence":"first","affiliation":[{"name":"University of Granada: Universidad de Granada","place":["SPAIN"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0357110","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}