Antibiotic Resistance Genes in Periodontitis

NCT07887204 | Active Not Recruiting

• 2 other identifiers: 2025/113 Rev-1TDK-2026-42374
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Periodontal Disease; Periodontitis; Antibiotic Resistance Genes

Keywords

oral microbiota; antibiotic resistance genes; periodontitis; oral biofilm; microbiome; shotgun metagenomics

Outcome Measures

Primary Outcomes (1)

• 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.

  Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)

Secondary Outcomes (6)

• Shannon diversity of antibiotic resistance genes (ARGs) in subgingival plaque

  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

  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)

  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

  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

  Single time point at baseline (day of subgingival plaque sampling; samples will be stored at -80°C and will be sequenced later)

Study Arms (2)

Individuals with Periodontitis

Individuals diagnosed with periodontitis who undergo periodontal examination and subgingival plaque sampling for the analysis of antibiotic resistance genes

Periodontally Healthy Individuals

Periodontally healthy individuals who undergo periodontal examination and subgingival plaque sampling for comparison of antibiotic resistance genes with the periodontitis group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Adults aged 18-65 years.
• Systemically healthy individuals.
• Non-smokers.
• No antibiotic use within the previous 6 months.
• No periodontal treatment within the previous 6 months.
• Willingness to participate and provide written informed consent.
• For the periodontally healthy group: full-mouth bleeding on probing score \<10%, probing depths ≤3 mm, no clinical attachment loss, and no radiographic bone loss.
• For the periodontitis group: detectable interdental clinical attachment loss at two or more non-adjacent teeth, or buccal/oral clinical attachment loss ≥3 mm with probing depths ≥3 mm at two or more non-adjacent teeth. Attachment loss must not be attributable to non-periodontal causes.

You may not qualify if:

• Presence of any systemic disease.
• Concomitant oral infections.
• Current smoking.
• Active infectious diseases, including acute hepatitis, AIDS, or tuberculosis.
• Malignancy or other systemic conditions that may affect periodontal tissues.
• Pregnancy or breastfeeding.
• Use of medications known to affect periodontal tissues, including phenytoin, cyclosporine A, or calcium channel blockers.
• Antibiotic use within the previous 6 months.
• Periodontal treatment within the previous 6 months.
• For the periodontitis group: apparent attachment loss attributable to traumatic gingival recession, cervical caries, distal attachment loss at second molars associated with third-molar malposition or extraction, endodontic lesions draining through the marginal periodontium, or vertical root fractures rather than periodontitis.

Sponsors & Collaborators

• Istanbul University: lead
• Scientific Research Project Coordination Unit of Istanbul University: collaborator

Study Sites (1)

Istanbul University Faculty of Dentistry

Istanbul, Turkey (Türkiye)

Location

Related Publications (2)

• Gager Y, Koppe J, Vogl I, Gabert J, Jentsch H. Antibiotic resistance genes in the subgingival microbiome and implications for periodontitis therapy. J Periodontol. 2023 Nov;94(11):1295-1301. doi: 10.1002/JPER.22-0696. Epub 2023 Jun 15.

  PMID: 37254939 BACKGROUND

• Arredondo A, Alvarez G, Isabal S, Teughels W, Laleman I, Contreras MJ, Isbej L, Huapaya E, Mendoza G, Mor C, Nart J, Blanc V, Leon R. Cross-sectional comparative shotgun metagenomic analysis of the subgingival resistome in healthy subjects and patients with periodontitis from four countries. J Oral Microbiol. 2026 Jan 7;18(1):2610588. doi: 10.1080/20002297.2025.2610588. eCollection 2026.

  PMID: 41522492 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Subgingival plaque samples collected from individuals, containing microbial DNA

MeSH Terms

Conditions

Periodontal Diseases; Periodontitis

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Periodontology

Study Record Dates

• First Submitted: October 15, 2026
• First Posted: October 21, 2026
• Study Start: February 24, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)