---
title: "Eubacterium saphenum and Periodontitis: Systematic Review Linking Detection to Disease Severity"
id: "plos-one-19-association-between-eubacterium-saphenum-and-periodontitis-a-systematic-review"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-19-association-between-eubacterium-saphenum-and-periodontitis-a-systematic-review"
content_type: "clinical_feed_article"
specialty: "Dentistry"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357110"
published_at: "2026-09-02T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Eubacterium saphenum and Periodontitis: Systematic Review Linking Detection to Disease Severity
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-19-association-between-eubacterium-saphenum-and-periodontitis-a-systematic-review
- **Specialty:** [Dentistry](https://medichelpline.com/clinical-feed/dentistry.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357110)
- **Published At:** 2026-09-02T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This systematic review assessed the association between **Eubacterium saphenum** and periodontitis, asking whether the taxon is more frequently detected or enriched in disease and whether abundance increases with severity. - The review followed PRISMA 2020 guidance and was prospectively registered in PROSPERO (CRD420251273182). - Inclusion criteria: observational studies of systemically healthy adults comparing periodontitis cases and periodontal health, reporting detection or relative abundance of **E. saphenum** in subgingival biofilm and/or saliva. - Searches covered multiple databases (PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, Google Scholar) with no date limits; first 200 Google Scholar results screened. - Eight observational studies met criteria, comprising 304 healthy controls and 510 periodontitis cases from Asia, Europe, and the Americas. - Detection platforms varied (PCR-based assays and high-throughput sequencing among those reported); across platforms, **E. saphenum** tended to be more frequently detected or present at higher relative abundance in periodontitis than in health. - Studies using the 2018 periodontal classification and reporting stage-specific analyses generally found higher detection or enrichment of **E. saphenum** in advanced disease (stages III–IV). - Quality and certainty: study quality was appraised with the AXIS tool; certainty of evidence was rated as low using GRADE due to observational and largely cross-sectional designs, methodological heterogeneity, and absent temporality. - Authors conclude a low-certainty positive directional association between **E. saphenum** and periodontitis—especially Stage III–IV—but note that longitudinal, interventional, and mechanistic studies are needed to establish temporality or functional contribution. - The review interprets findings within a polymicrobial dysbiosis framework and emphasizes that current evidence supports association, not causation.
## Clinical Analysis & Structured Key Points
Association between Eubacterium saphenum and periodontitis: A systematic review | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Peer Review Reader Comments Figures Figures Abstract Objective 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 Eubacterium saphenum and the severity of periodontitis. Methods 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 E. saphenum 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. Results Eight observational studies (304 healthy controls vs. 510 periodontitis cases) from Asia, Europe, and the Americas met the inclusion criteria. Across multiple detection platforms, E. saphenum 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 E. saphenum 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. Conclusions Low-certainty evidence suggests a positive directional association between E. saphenum and periodontitis, particularly in advanced Stage III–IV disease. However, longitudinal, interventional, and mechanistic studies are required to clarify temporality and determine whether E. saphenum contributes functionally to periodontal dysbiosis or primarily represents a marker of established disease. Citation: Al-Rihaymee S, Abdulbaqi HR, Abdulkareem AA, Harun WHAW, Baharuddin NA (2026) Association between Eubacterium saphenum and periodontitis: A systematic review. PLoS One 21(9): e0357110. https://doi.org/10.1371/journal.pone.0357110 Editor: Antonio Magan-Fernandez, University of Granada: Universidad de Granada, SPAIN Received: April 17, 2026; Accepted: August 12, 2026; Published: September 2, 2026 Copyright: © 2026 Al-Rihaymee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the paper and its Supporting Information file. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. 1. Introduction Periodontitis is initiated by the polymicrobial biofilm, but disease progression reflects a dysregulated host response largely determined by genetic and environmental factors [ 1 – 3 ]. Although established periodontal pathobionts, including Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola , Aggregatibacter actinomycetemcomitans , Fusobacterium nucleatum , and Filifactor alocis , have been widely implicated in periodontitis, their detection alone does not fully explain inter-individual variation in disease severity or progression, supporting a community-level dysbiosis model of disease [ 4 – 9 ]. Contemporary models therefore emphasise polymicrobial synergy and dysbiosis, in which shifts in microbial community structure and function, together with host inflammatory responses, drive periodontal tissue destruction rather than the activity of a single causative species [ 10 , 11 ]. This paradigm highlights the need to investigate non-classical microbial taxa that may act as markers of disease severity or as members of dysbiotic microbial consortia within the subgingival ecosystem. Within this context, emerging non-classical anaerobic taxa such as E. saphenum deserve focused evaluation because they may provide additional insight into dysbiotic pocket ecology and disease-severity patterns beyond the classical periodontal pathogen complexes. E. saphenum is a Gram‑positive obligate anaerobe, originally isolated from human periodontal pockets [ 12 ]. Its relevance to periodontitis is biologically plausible because it is suited to the low-redox, anaerobic environment characteristic of deep periodontal pockets and has been associated with asaccharolytic and proteolytic oral microbial communities [ 12 , 13 ]. Although E. saphenum is not traditionally included among established periodontal pathogens, it has been increasingly detected through molecular diagnostic approaches, including PCR-based assays and high-throughput sequencing platforms [ 14 – 16 ]. More recent studies have reported E. saphenum enrichment in periodontitis, particularly in advanced disease [ 17 , 18 ]. Several clinically and biologically relevant considerations support the appraisal of E. saphenum as an emerging non-classical periodontal taxon. First, it occupies an ecological niche directly relevant to advanced periodontal dysbiosis. Second, it has been repeatedly detected in periodontitis despite not being part of the classical periodontal pathogen groups. Third, the available evidence remains fragmented across different populations, sample types, periodontal diagnostic criteria, and microbial detection platforms. Therefore, the key gap is whether the repeated detection of E. saphenum reflects a reproducible severity-associated component of periodontal dysbiosis, particularly in advanced periodontitis, and how this taxon should be interpreted within the broader polymicrobial dysbiosis framework. Given the observational nature of the available evidence, findings in this review were interpreted as associations rather than evidence of causality. Accordingly, this review interprets E. saphenum within an ecological dysbiosis framework, distinguishing evidence for association from evidence for temporality, pathogenicity, or causal contribution. We hypothesised that E. saphenum would be more frequently detected or enriched in periodontitis than in periodontal health and that its detection or abundance would be higher in advanced disease, supporting its potential role as a marker of dysbiotic progression rather than as a confirmed primary pathogen. Focused Question Is E. saphenum associated with periodontitis compared with periodontal health, and does its abundance increase with disease severity? 2. Methods The present systematic review was conducted and reported in accordance with the recommendations of the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement [ 19 ]. The study was prospectively registered with PROSPERO (ID: CRD420251273182). PECO: Population: systemically healthy adult participants; Exposure: individuals diagnosed with periodontitis (based on recognised clinical classification systems, including the 1999 AAP or 2018 EFP/AAP frameworks); Comparator: individuals with periodontal health; Outcome: detection, prevalence or relative abundance of E. saphenum in subgingival biofilm samples and/or saliva samples. Eligible study designs included observational studies (cross-sectional and case–control studies) reporting original clinical data. 2.1. Eligibility criteria Only the studies that met the following criteria were considered: availability of full text online; in vivo original articles; the laboratory confirmation of the presence of E. saphenum ; systemically healthy participants; comparison of healthy controls versus periodontitis; or presenting an unambiguous assessment of the association between E. saphenum and periodontitis. Studies were excluded if they involved non-human participants, lacked a comparison between periodontitis and healthy groups, or reported outcomes irrelevant to periodontitis or E. saphenum ; had unclear definitions of periodontitis; or were case reports/series, review articles, or in vitro studies. 2.2. Search strategy A comprehensive search of PubMed/MEDLINE, Scopus, Web of Science Core Collection, the Cochrane Library, and Google Scholar was conducted between June and September 2025, with no restrictions on publication date. For the Google Scholar search results, the first 200 references, representing the first 20 pages, were screened [ 20 ]. The keywords used in the search were: ( Eubacterium saphenum OR E. saphenum OR E . saphenus ) AND (periodontitis OR periodontal disease). The records of all sources were exported in RIS/BibTeX format and merged in Zotero. Duplicates (i.e., those identified by the search strategy across multiple databases) were removed in Zotero and Rayyan using a hierarchical protocol as follows: 1) exact DOI or PMID/PMCID match; 2) normalise title, first author, and publication year; and 3) screen the records based on titles and abstracts. After removing duplicates, all ineligible articles were excluded, with the reasons for exclusion recorded. A total of eight eligible articles were included in the final review, as shown in the PRISMA flow chart ( Fig 1 ). Download: PNG larger image TIFF original image Fig 1. PRISMA flow diagram of the study-selection process. n denotes the number of records or studies, as applicable. https://doi.org/10.1371/journal.pone.0357110.g001 2.3. Data extraction The data from each study were extracted and synthesised by two researchers (S.A. and H.R.A.) in an independent and standardised manner. Additionally, the studies were screened by an independent reviewer (A.A.A). For each study included, the following data were collected: (1) author(s) and year of publication, (2) location of the study, (3) study design, (4) periodontal diagnosis as defined in each article, (5) population (sample size), (6) type of sample (subgingival dental biofilm and/or saliva), (7) detection methods, (8) association of E. saphenum with periodontitis severity, (9) quantitative/statistical finding, and (10) main findings. 2.4. Quality assessment, risk of bias, and Certainty of Evidence of the included articles The quality assessment score and the transparency of the reporting of all eligible studies in this review were critically evaluated utilising the AXIS tool [ 21 ]. The AXIS tool was selected because the included studies were observational and predominantly cross-sectional in design, involving comparisons of microbial detection or relative abundance between periodontal health and periodontitis groups. Although the Joanna Briggs Institute checklist is also appropriate for analytical cross-sectional studies, AXIS was chosen because it provides a broader 20-item framework for evaluating both methodological quality and reporting transparency, including sample-size justification, sampling frame, representativeness, non-response, limitations, ethical approval, and potential conflicts of interest. This approach is consistent with methodological guidance recommending that appraisal tools should be selected according to the design and methodological characteristics of the included studies [ 22 ]. The AXIS tool, designed for observational studies, comprises twenty questions with a possible response of yes, no, or don't know for each question (for calculation purposes, yes = 1, no/don't know = 0). A quality score out of 20 was then generated based on the sum of these responses. The following guidelines were used: scores indicating low quality = 1–7; medium quality = 8–14; high quality = 15–20. A quantitative meta-analysis was not performed because the included studies showed substantial clinical and methodological heterogeneity in sample matrix, microbial detection platform, periodontal case definition, disease-severity classification, and microbial outcome reporting. Instead, a structured qualitative synthesis was performed. Studies were compared according to five predefined domains: biological sample type, detection method, periodontal diagnostic framework, microbial outcome metric, and availability of severity-specific analysis. To reduce subjectivity in the qualitative synthesis, these domains were extracted systematically for each included study. The biological sample type was classified as saliva or subgingival biofilm. The detection platform was classified as qPCR, 16S rRNA sequencing, HOMIM microarray, or chequerboard DNA-DNA hybridisation. Periodontal diagnosis was classified according to whether studies used the 2018 EFP/AAP classification, the 1999 AAP framework, or study-specific clinical thresholds. Microbial outcomes were classified as detection, prevalence, relative abundance, absolute quantification, or correlation with clinical periodontal parameters. Severity-specific analysis was recorded where studies compared early/mild disease with advanced periodontitis. The certainty of evidence for the association between E. saphenum and periodontitis was assessed using the GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation) at the outcome level. The body of evidence was judged to start at low certainty because the included studies were observational, and it was then assessed across the standard GRADE domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias. Potential upgrading factors, including large estimates and severity-related patterns, were considered descriptively. However, because cross-study agreement could only be assessed qualitatively across heterogeneous methodologies, consistency was not used as a formal upgrading criterion. Final certainty ratings (very low/low/moderate/high) were assigned to the body of evidence for the outcome [ 23 , 24 ]. 3. Results 3.1. Included studies Following PRISMA guidelines, database searches identified 753 records, with no additional sources retrieved. After deduplication, a total of 462 unique records remained, which were then screened by title and abstract, resulting in the exclusion of 421 records. The remaining forty-one full-text articles were then assessed for eligibility. Thirty-three articles were excluded for the following predefined reasons: absence of a healthy control group (n = 5), review articles (n = 2), master's theses (n = 2), systemic diseases (n = 4), animal studies (n = 1), taxonomic studies (n = 3), (n = 6) for studies with an unclear definition of periodontitis, and (n = 10) for other reasons, including studies of (pregnant women, elderly populations, laboratory-only investigations, root-canal research, and peri-implantitis). Ultimately, eight studies that met the inclusion criteria were incorporated into the qualitative synthesis, as shown in ( Fig 1 ). 3.2. Study designs, periodontal conditions/samples evaluated, and examiner calibration The included studies were conducted in Asia (China and South Korea), Europe (Spain and Sweden), and the Americas (USA, Brazil, and Colombia). The study arms consisted of periodontal health controls and patients with periodontitis, with a total of 304 and 510 participants, respectively. Clinical heterogeneity was evident across the included studies. Although all studies compared periodontal health with periodontitis, they did not use identical diagnostic frameworks. Four studies used the 2018 EFP/AAP classification, two studies used the 1999 AAP framework, and two studies used study-specific clinical definitions based on combinations of probing pocket depth, clinical attachment loss, bleeding on probing, and radiographic bone loss. This variation limits direct comparability between studies because “periodontitis” did not represent an identical clinical construct across all included investigations. Saliva or subgingival biofilm samples were used to assess E. saphenum detection, abundance, or microbial profiles. Two studies collected saliva samples from 80 periodontal health participants and 74 participants with periodontitis [ 25 , 26 ]. A total of 224 and 436 subgingival biofilm samples were collected from participants with periodontal health and periodontitis, respectively [ 16 – 18 , 27 – 29 ], Table 1 . These subgingival biofilm samples were processed either individually in one study [ 27 ] or pooled in four studies [ 16 – 18 , 28 ]. Download: PNG larger image TIFF original image Table 1. Summary of the publications included for analysis of the association between E. saphenum and periodontitis. https://doi.org/10.1371/journal.pone.0357110.t001 The definition of periodontitis cases varied across the included studies. Two studies [ 26 , 29 ] defined periodontitis using probing pocket depth (PPD) thresholds (PPD ≥ 4–6 mm) and bleeding on probing (BOP), alongside CAL and radiographic bone loss [ 30 ]. Two other studies used the 1999 AAP framework [ 27 , 28 ]. The 2018 EFP/AAP staging system [ 1 , 31 , 32 ] was applied by four of the studies [ 16 – 18 , 25 ], establishing comparisons according to periodontitis severity (stages I-II vs. III-IV), Table 1 . Among the included studies, examiner calibration was reported in only five studies [ 16 – 18 , 27 , 28 ]. Reducing measurement errors in recording PPD and CAL is necessary to define cases and sampling sites. 3.3. Method of detection The included studies showed substantial heterogeneity in the detection methods of E. saphenum . Several investigations utilised 16S rRNA gene sequencing to characterise bacterial communities [ 17 , 25 , 26 ]. In contrast, Vieira Colombo et al. (2016) applied checkerboard DNA–DNA hybridisation targeting 39 bacterial taxa, including E. saphenum [ 27 ]. Other studies focused on targeted quantitative PCR (qPCR) for specific pathogen detection, as reported by Lafaurie et al. (2023) and Castillo et al. (2023), both of which collected subgingival biofilm samples by paper points [ 16 , 18 ]. Additionally, Cui et al. (2019) implemented a Human Oral Microbe Identification Microarray (HOMIM) based on 16S species-specific probes to evaluate bacterial composition in samples from generalised aggressive periodontitis cases [ 28 ]. Similarly, Marchesan et al. (2015) used the HOMIM microarray to profile the periodontal microbial community [ 29 ]. Overall, variable methods were utilised in these studies for detecting E. saphenum, as shown in Table 1 . These platform differences may introduce detection bias because targeted methods, such as qPCR, HOMIM and chequerboard DNA–DNA hybridisation, depend on predefined primers or probes, whereas 16S rRNA sequencing is affected by primer choice, amplified region, sequencing depth, database selection and bioinformatic pipeline [ 18 , 25 , 27 – 29 ]. Consequently, qPCR copy number, HOMIM/chequerboard signal intensity and sequence-derived relative abundance should not be interpreted as directly equivalent outcomes. 3.4. Microbial data A structured qualitative synthesis was undertaken to summarise the direction and type of evidence across the included studies. At the study level, all eight included studies contributed findings in a positive qualitative direction for E. saphenum in relation to periodontitis, advanced disease, or periodontal disease-associated microbial profiles. However, the studies supported this pattern in different ways. Some studies reported increased detection, abundance, or enrichment in periodontitis or advanced disease, whereas others reported correlations with periodontal clinical parameters or microbial-community associations. Severity-specific evidence was available in three studies, all of which sup
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