The Peri-Implantitis Microbiome: A Review

Key Takeaways

• Distinct Microbial Profile in Peri-Implantitis: While peri-implantitis shares key periodontal pathogens (P. gingivalis, T. forsythia, T. denticola) with periodontitis, it also involves implant-specific and opportunistic microbes like Staphylococcus epidermidis and Filifactor alocis. It is a polymicrobial infection, meaning there is no single bacteria responsible.
  
  
•   Microbial Biomarkers and Risk Assessment: A combination of bacterial species, including those in the proposed "Peri-Implantitis-Related Complex (PiRC)," may serve as biomarkers for disease risk and progression. High-throughput sequencing studies suggest that tracking these microbes could help clinicians with early diagnosis and targeted interventions.

Introduction

Peri-implantitis is a biofilm-driven inflammatory condition leading to the loss of supporting bone around dental implants [1,2]. It affects roughly 20% of implant patients, making it a significant complication of implant therapy [3]. Early studies assumed peri-implantitis was microbiologically similar to periodontitis, given the comparable clinical inflammation [4]. However, emerging evidence suggests the peri-implant microbiome has unique features influenced by the implant’s titanium surface and local environment [5,6]. This review analyzes current literature on the peri-implantitis microbiome, prioritizing recent high-impact human studies. 

Key Bacterial Species and Risk Assessment Implications

Synthesizing the literature, certain microbes consistently emerge as primary players in peri-implantitis and could serve as future biomarkers or therapeutic targets:

• Porphyromonas gingivalis: Widely recognized for its proteolytic virulence factors, P. gingivalis is strongly linked to peri-implant tissue destruction [7,9].

• Tannerella forsythia: Another “red complex” member frequently detected in peri-implantitis; correlates with deeper pockets and advanced lesions [6,7].

• Treponema denticola: Motile spirochete that often synergizes with P. gingivalis, found in higher proportions at diseased implants [6,9].

• Fusobacterium nucleatum: Keystone bridging organism that increases biofilm complexity; distinct subspecies show strong associations with peri-implantitis severity [9,10].

• Prevotella intermedia (and other Prevotella spp.): Noted in many peri-implantitis profiles [7,9]. P. intermedia can co-occur with P. gingivalis in complex subgingival communities.

• Staphylococcus epidermidis: Possibly an opportunistic pathogen on implant surfaces. Recent meta-analysis found high odds of detection in peri-implantitis [7,13].

• Filifactor alocis / Filifactor fastidiosus: Emerging Gram-positive anaerobes, increasingly implicated by high-throughput studies [9,12]. May contribute to therapy-resistant infections.

Detection of these species—particularly in higher loads—could help clinicians gauge risk or progression. While no single organism guarantees disease, their collective presence signals a dysbiotic shift [7,9]. Importantly, the presence of these microbes must be interpreted alongside clinical signs and host factors, as some patients harbor periopathogens but remain stable [6,16].

Microbiome Profiles in Peri-Implantitis vs. Health

Common Periodontal Pathogens in Peri-Implantitis

Multiple studies consistently show that classical periodontal pathogens are prevalent at peri-implantitis sites. High-impact systematic reviews and meta-analyses, such as those in Clinical Oral Implants Research [7], report significant associations between peri-implantitis and Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. These three species—known as the “red complex” [8]—are traditionally implicated in periodontitis, and modern DNA sequencing studies reinforce their link to peri-implant disease [9]. For example, a strain-level metagenomic analysis in NPJ Biofilms and Microbiomes identified P. gingivalis, T. forsythia, and T. denticola among the top discriminating species in peri-implantitis [9]. Their presence is not incidental; in many samples, their cumulative abundance strongly distinguishes peri-implantitis from healthy implant sites [7,9].

Additional Species Enriched in Disease

Beyond these classical periodontal microbes, peri-implantitis biofilms often harbor additional anaerobic and opportunistic species. One study [9] proposed a “peri-implantitis-related complex (PiRC)” that included Prevotella intermedia, Prevotella endodontalis, Fusobacterium nucleatum, and Filifactor fastidiosus—taxa newly highlighted as strong discriminators of peri-implantitis. F. nucleatum, in particular, is considered a keystone species bridging early and late colonizers, and it often blooms in sites progressing from peri-implant mucositis to peri-implantitis [10,11]. Similarly, emerging anaerobes like Filifactor alocis (historically underdetected in culture-based studies) have been found in significant abundance at diseased implant sites [12]. Overall, these findings underline that peri-implantitis is driven by a polymicrobial community dominated by classic periopathogens plus additional strict anaerobes that flourish in the unique implant environment [5,7,9].

Opportunistic and Implant-Specific Microbes

Several bacteria uncommon in natural teeth have also been detected around failing implants. For instance, Staphylococcus epidermidis—a skin commensal—shows a strong association with peri-implantitis in a recent meta-analysis [7,13]. Whether it actively drives disease or acts as an opportunistic colonizer remains debated, but its high odds ratio suggests a role in implant-associated dysbiosis [7]. Other opportunists (e.g., Streptococcus aureus, enteric rods, yeasts) appear sporadically but lack consistent enrichment patterns [7]. Overall, the microbial evidence indicates that peri-implantitis involves mixed anaerobic communities, sometimes joined by opportunistic species that exploit the foreign-body environment [9,13].

Microbiome of Healthy Implants

By contrast, healthy peri-implant sites tend to be colonized by more benign or early-colonizing bacteria [5,9,14]. In one survey co-authored by expert Georgios Kotsakis, healthy implants were characterized by Streptococcus, Haemophilus, and certain Prevotella species [5]. Another review noted that Veillonella and Neisseria are commonly associated with peri-implant health and often decrease as disease severity increases [14]. Generally, healthy implants harbor more aerobic or facultative organisms, whereas peri-implantitis is associated with a shift toward predominantly anaerobic taxa [9,14]. Moreover, peri-implantitis sites often exhibit higher overall bacterial diversity than healthy sites, reflecting the influx of diverse obligate anaerobes once the local environment becomes more suitable to their survival [9,15].

Differences from Periodontitis

A critical question is whether the peri-implantitis microbiome truly differs from periodontitis. Historically, culture-based studies suggested no unique peri-implant pathogen that was absent in periodontitis [16]. More modern methods hint at subtle differences: for instance, peri-implantitis sites often harbor a higher abundance of Porphyromonas and Treponema while featuring less Aggregatibacter actinomycetemcomitans compared to periodontitis [7,9]. Kotsakis, in a Periodontology 2000 review, argued that peri-implantitis should not be considered “periodontitis on an implant,” emphasizing that titanium surfaces and metal ion release create a unique habitat [6]. Indeed, peri-implantitis lesions frequently resist antibiotic regimens effective for periodontal disease, implying a distinct microbial ecology and possibly enhanced antibiotic resistance [6].

Notable Studies and Evidence Strength

A variety of cross-sectional, longitudinal, and systematic reviews inform our current understanding. Below are some of the key studies ranked by journal impact, author credibility, and citation influence:

1. Ghensi et al. (2020, NPJ Biofilms Microbiomes)
   
   

• High-impact journal, advanced methods (shotgun metagenomics): Examined 113 plaque samples from 72 individuals and identified a seven-species “PiRC” complex strongly associated with peri-implantitis [9]. Co-authored by leading microbiome scientists, it represents a landmark in applying strain-level metagenomics to peri-implant studies.

2. Ferreira et al. (2023, Clin Oral Implants Res)
   
   

• Rigorous systematic review & meta-analysis: Pooled 12 cross-sectional human studies (~1,233 participants) to identify microbes significantly associated with peri-implantitis [7]. Found strong associations for S. epidermidis, F. nucleatum, T. denticola, T. forsythia, P. intermedia, and P. gingivalis. This meta-analysis is highly regarded for its statistical approach and transparent bias assessment.

3. Daubert et al. (2018, Clin Implant Dent Relat Res)
   
   

• Human study linking titanium to microbial shifts: Analyzed 15 implants (6 peri-implantitis, 9 healthy) using 16S rRNA gene sequencing and correlated findings with titanium particle levels [5]. Despite a smaller sample, the study stands out for directly measuring titanium debris. Findings indicated a marked increase in Veillonella at diseased sites, with Streptococcus, Prevotella, and Haemophilus dominating healthy sites.

4. Ghensi et al. (2024, in review)
   
   

• Longitudinal shotgun metagenomic study: Expanded sample (91 subjects, 320 metagenomes) to track how the peri-implant microbiome evolves with treatment [17]. Preliminary data indicate that mechanical therapy partially restores a healthier microbial composition, supporting the notion that reducing dysbiotic taxa (especially PiRC species) correlates with clinical improvement.

5. Song et al. (2024, BMC Oral Health)
   
   

• Metagenomic cross-sectional design with functional insights: Surveyed 40 patients using shotgun sequencing and found peri-implantitis sites harboring the red-complex bacteria plus P. endodontalis [18]. Detected upregulation of flagellar assembly genes in diseased samples, suggesting motility-related invasion may characterize peri-implantitis.

These studies collectively demonstrate that modern high-throughput sequencing (especially shotgun metagenomics) is elevating our understanding of peri-implant microbial communities [9,17,18]. They reinforce that while classical periodontal pathogens predominate in peri-implantitis, a unique consortium enriched in anaerobes and opportunistic species differentiates it from health—and likely from periodontitis [6,7,9].

Microbiome Analysis Methods: 16S vs. Shotgun Metagenomics

16S rRNA Gene Sequencing

Most earlier peri-implant microbiome studies relied on 16S rRNA sequencing, which amplifies a segment of the bacterial 16S gene [5,13,16]. While cost-effective and suitable for broad surveys, it generally resolves bacteria at the genus or “phylotype” level [9,22]. PCR biases and limited reference databases can distort quantitative results, making it challenging to differentiate closely related species. Consequently, 16S-based findings that, for instance, link “Prevotella spp.” to peri-implantitis may be missing the specific culprit species [16,22]. Nonetheless, 16S studies have been invaluable for revealing major shifts in microbial composition and diversity between peri-implant health and disease [5,7].

Shotgun Metagenomic Sequencing

Shotgun metagenomics sequences all DNA in a sample, enabling strain-level resolution, functional gene profiling, and detection of non-bacterial taxa [9,17,18]. This approach overcomes many 16S limitations, capturing a richer genomic picture. For example, Ghensi et al. [9] identified distinct F. nucleatum subspecies correlating with disease severity, a precision impossible via short-read 16S. Functional analysis can reveal pathways upregulated in peri-implantitis, such as flagellar assembly or beta-lactam resistance genes [18]. However, shotgun metagenomics is more expensive, data-intensive, and prone to host-DNA contamination [9,17]. Many studies therefore have smaller sample sizes. Despite these challenges, the method is considered the gold standard for comprehensive microbial characterization [22].

Other Techniques

Additional methods range from DNA–DNA hybridization (“checkerboard”)—common in older peri-implant studies—to advanced culture-based “culturomics” [16]. Although these techniques have historical or niche applications, modern research increasingly favors high-throughput sequencing. The strongest future direction may combine 16S and shotgun approaches with functional assays, multi-omics, and robust bioinformatics pipelines to fully elucidate peri-implant microbial ecology [17,18].

Conclusion

Recent research underscores the pivotal role of microbial dysbiosis in peri-implantitis, involving a polymicrobial ecosystem enriched in classical periodontal pathogens (P. gingivalis, T. forsythia, T. denticola) plus opportunistic and implant-specific taxa (F. nucleatum, S. epidermidis, etc.) [7,9]. While the microbiome overlaps with periodontitis, multiple high-impact studies and reviews argue that peri-implantitis is not simply “periodontitis on an implant” [6]. Titanium surfaces, corrosion products, and local immune responses create a distinctive environment fostering antibiotic-resistant communities [6,21].

Advances in high-throughput sequencing are improving our understanding of peri-implant microbial structure and function, revealing that no single bacterial driver universally explains peri-implantitis [7,9,17]. Rather, a polymicrobial synergy disrupts host homeostasis, consistent with other complex inflammatory diseases. Nonetheless, certain bacterial consortia (e.g., the PiRC seven-species complex) appear repeatedly and may serve as biomarkers or therapeutic targets in peri-implantitis risk assessment [9]. Monitoring these pathogens, possibly via chairside tests, could guide early interventions—especially in individuals with a history of periodontitis or other risk factors.

Methodologically, shotgun metagenomics now affords species-level resolution and functional insights, enabling more precise identification of key taxa and pathways driving peri-implantitis [9,18,22]. Further adoption of these approaches, coupled with standardized diagnostic criteria and longitudinal designs, will clarify whether specific bacterial signatures can predict disease onset or measure treatment response. Integrating host–microbe data (immune markers, genetic predispositions) into personalized peri-implant care is a logical next step, given the multifactorial nature of this disease [6,14].

In sum, the current body of evidence strongly supports a microbial etiology for peri-implantitis characterized by a distinct but overlapping set of pathogens relative to periodontitis. Clinicians can leverage these insights to refine risk assessment, prophylaxis, and therapeutic protocols, while researchers continue to unravel the nuances of this evolving peri-implant microbiome. The ultimate aim is a preventive, evidence-based approach that safeguards implant longevity by preserving—or restoring—microbial balance before irreversible tissue destruction occurs.

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