An observational study in Periodontal Disease, Periodontitis and Antibiotic Resistance Genes, sponsored by Istanbul University. Active, not recruiting at 1 site in Turkey (Türkiye). Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Istanbul University · Observational
Antimicrobial resistance (AMR) is a major global public health concern, and the oral microbiome may serve as an important reservoir of antibiotic resistance genes (ARGs). Periodontitis is a chronic inflammatory disease characterized by dysbiosis of the subgingival microbiome and progressive destruction of tooth-supporting tissues. The complex microbial communities within subgingival biofilms may facilitate the exchange of ARGs through horizontal gene transfer (HGT), potentially contributing to the dissemination of antimicrobial resistance.
This observational study aims to comparatively investigate the microbial composition, antibiotic resistance gene profiles, and associated mobile genetic elements (MGEs) in the subgingival microbiomes of periodontally healthy individuals and patients with periodontitis using shotgun metagenomic sequencing.
Subgingival plaque samples will be collected from 50 participants, including 25 periodontally healthy individuals and 25 patients diagnosed with periodontitis, attending Istanbul University Faculty of Dentistry. Following microbial DNA extraction, shotgun metagenomic sequencing will be performed to characterize the taxonomic and functional composition of the subgingival microbiome. Bioinformatic analyses will be conducted using established databases and tools, including CARD, RGI, ARGs-OAP, MobileElementFinder, PlasmidFinder, ICEberg, and ISfinder, to identify ARGs, characterize MGEs, and investigate their potential associations.
The study will compare the diversity, abundance, and distribution of ARGs and MGEs between the two groups and assess the potential relationship between periodontal dysbiosis and the genetic capacity for horizontal transfer of antibiotic resistance.
By providing a comprehensive characterization of the subgingival resistome and its associated mobile genetic elements, this study aims to improve understanding of the potential contribution of periodontal disease to antimicrobial resistance and provide scientific evidence supporting the rational use of antibiotics in periodontal care.
Antibiotic resistance is recognized today as one of the most serious global threats to public health. Worldwide, it has been documented that in 2019, 1.27 million deaths were directly attributable to bacterial antibiotic resistance, and 4.95 million deaths were associated with it. Bacteria can acquire antibiotic resistance not only through spontaneous mutations but also through horizontal gene transfer (HGT). HGT refers to the transfer of resistance genes between different bacterial species. This transfer occurs through transformation, conjugation, or transduction, and via mobile genetic elements (MGEs) such as plasmids, transposons, and bacteriophages. The excessive and inappropriate use of antibiotics is one of the main triggers for the emergence of antibiotic resistance. When antibiotics become ineffective, bacteria cannot be suppressed, and the dissemination of resistance genes between bacterial populations accelerates through HGT. This leads to the emergence of super-resistant bacterial strains and a reduction in the efficacy of antibiotic therapies. Periodontitis is a multifactorial, chronic inflammatory disease characterized by the destruction of periodontal tissues supporting the tooth. The prevalence and rate of progression of periodontitis are closely related to complex interactions between periodontopathogenic bacteria and host immune cells. In periodontal health, Gram-positive bacteria such as Actinomyces and Streptococcus dominate the dental plaque biofilm, forming a balanced ecosystem in homeostasis with host cells. Disruption of this homeostasis leads to environmental changes that cause a dysbiotic shift in the biofilm composition. The subgingival biofilm constitutes the primary etiological factor of periodontal disease. The management of periodontal diseases mainly relies on the removal of subgingival biofilm. Mechanical therapy is generally effective in eliminating biofilm and resolving inflammation. However, in certain patient groups (e.g., young adults with rapidly progressing disease) and clinical situations (e.g., acute periodontal abscesses or necrotizing periodontal diseases accompanied by systemic manifestations), mechanical therapy alone may be insufficient to achieve successful outcomes. As stated in the 2017 Classification of Periodontal and Peri-implant Diseases and Conditions and in the European Federation of Periodontology (EFP) S3-level Clinical Practice Guideline for the Treatment of Stage I-III Periodontitis, adjunctive antibiotic therapy is beneficial in such cases. From this perspective, while antibiotics play an important role in periodontal therapy, periodontal diseases themselves may also contribute to the global rise in antimicrobial resistance (AMR). Possession of a specific antibiotic resistance gene (ARG) by a bacterium indicates that the bacterium has the ability to protect itself against, or neutralize, the corresponding antibiotic. This information reflects the bacterial genotype associated with antibiotic resistance and is of great importance for evaluating the antimicrobial resistance (AMR) profile.
In this study, the total genomic DNA of microorganisms isolated from the subgingival biofilms of periodontitis and healthy individuals will be sequenced, and through bioinformatic analyses, the microbial diversity, genetic composition, antibiotic resistance gene profiles, and associated mobile genetic elements (MGEs) of the subgingival microbiome will be comprehensively characterized using shotgun metagenomic techniques. Thus, the study will not only reveal the presence of resistance genes in periodontitis but also their potential for mobility and HGT. The shotgun metagenomic approach surpasses classical 16S rRNA analyses by enabling the identification of microbial communities at both species and gene levels. In this context, the sequencing data obtained will be compared against up-to-date databases such as CARD, RGI, ARGs-OAP, MobileElementFinder, PlasmidFinder, ICEberg, and ISfinder, to evaluate the distribution, diversity, and association of resistance genes with MGEs within the microbiota. Within the scope of this project, subgingival plaque samples from 25 healthy and 25 periodontitis subjects attending Istanbul University Faculty of Dentistry will be collected. After DNA isolation, shotgun metagenomic analyses will be performed to determine the presence, genetic organization, and HGT-mediated dissemination potential of ARGs. The sequencing data will be analyzed using bioinformatic methods to investigate both the bacterial potential for spreading resistance genes via HGT and possible increases in this transfer potential within the dysbiotic flora.
The results obtained from this project will contribute to understanding the relationship between periodontal diseases and antibiotic resistance, providing scientific evidence that supports rational antibiotic use in periodontal therapy.
The findings of this study will enhance our understanding of the role of the oral microbiota in resistance mechanisms and may assist in developing new strategies to improve the efficacy of antibiotic treatments.
In this way, the project aims to promote more conscious and evidence-based antibiotic use in the management of periodontal diseases.
855 studies on the registry are indexed under Periodontal Diseases; 189 are open to participants now.
This study's enrollment of 50 is below the median of 100 across 300 observational studies indexed under Periodontal Diseases.
Browse Periodontal Diseases studies →Istanbul University is the lead sponsor of 507 studies on the registry; 80 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 1 (20%) have results posted.
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The study population will consist of systemically healthy, non-smoking adults aged 18-65 years attending the Department of Periodontology, Faculty of Dentistry, Istanbul University, Istanbul, Türkiye, who have not used antibiotics within the previous 6 months. Participants will include individuals with periodontitis and periodontally healthy individuals who meet the study eligibility criteria.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Individuals diagnosed with periodontitis who undergo periodontal examination and subgingival plaque sampling for the analysis of antibiotic resistance genes
Periodontally healthy individuals who undergo periodontal examination and subgingival plaque sampling for comparison of antibiotic resistance genes with the periodontitis group
Richness of antibiotic resistance genes (ARGs) in subgingival plaque
RG diversity, operationalized as ARG richness (the number of distinct ARGs per sample), assessed by Oxford Nanopore shotgun metagenomic sequencing of pooled subgingival plaque after host DNA depletion. ARGs are annotated using CARD/RGI. To account for differences in bacterial biomass between groups, ARG tables are normalized by rarefaction to an equal bacterial read depth (after host read removal), and sequencing depth and host DNA percentage are reported for each sample. ARG richness is compared between periodontitis patients and periodontally healthy individuals.
Time frame: Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)
Shannon diversity of antibiotic resistance genes (ARGs) in subgingival plaque
Alpha diversity of the ARG profile, measured by the Shannon index, from Oxford Nanopore shotgun metagenomic data annotated with CARD/RGI. The index is calculated after rarefaction to an equal bacterial read depth (after host read removal) and compared between periodontitis patients and periodontally healthy individuals.
Time frame: Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)
Composition and relative abundance of ARGs in subgingival plaque
ARG relative abundance (normalized read counts, e.g., per Gb of bacterial reads) and beta diversity (PCoA) of ARG profiles, annotated with CARD/RGI and ARGs-OAP, compared between periodontitis and healthy groups.
Time frame: Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)
Presence, diversity and ARG co-localization of mobile genetic elements (MGEs)
Plasmids, insertion sequences and integrative conjugative elements identified using PlasmidFinder, ISfinder, ICEberg and MobileElementFinder. Co-localization of MGEs with ARGs on the same long reads or contigs is assessed and compared between groups.
Time frame: Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)
Horizontal gene transfer (HGT) potential of ARGs and its association with ARG diversity
HGT potential is estimated from the proportion of ARGs co-localized with MGEs. It is compared between periodontitis and healthy groups, and its association with ARG diversity is evaluated within each group.
Time frame: Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)
Taxonomic composition and diversity of subgingival microbiota
Alpha and beta diversity and taxonomic profiles from shotgun metagenomic data, with taxonomic assignment integrated with the Human Oral Microbiome Database (HOMD), compared between periodontitis and healthy groups.
Time frame: Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)
Correlation between ARG profiles and clinical periodontal parameters
Correlation of ARG diversity and composition with plaque index (PI), gingival index (GI) and probing pocket depth (PPD), clinical attachment loss (CAL), mobility in periodontitis patients.
Time frame: Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)
Plan to share: No — The study data will be shared through publication of the results in a peer reviewed scientific journal.
Started Feb 2026 (actual). Primary completion is estimated for Dec 2026, 10 months after the start.
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