Effects of Adjunctive Synbiotic Supplementation to Non-Surgical Periodontal Therapy in Smokers With Periodontitis

June 24, 2026 updated by: Burcu KARADUMAN, Biruni University

Effects of Adjunctive Synbiotic Supplementation to Non-Surgical Periodontal Therapy on Clinical, Immunological, and Microbiological Parameters in Smokers With Periodontitis

The aim of this study is to evaluate the effects of adjunctive synbiotic supplementation combined with non-surgical periodontal therapy in smokers with periodontitis. The main questions this study aims to answer are:

Does adjunctive synbiotic supplementation improve clinical periodontal parameters in smokers with periodontitis? Does adjunctive synbiotic supplementation affect immunological and microbiological parameters associated with periodontal disease?

Systemically healthy smokers and non-smokers diagnosed with generalized Stage III-IV Grade B/C periodontitis will be included in the study. Participants will first be divided into two main groups according to smoking status (smokers and non-smokers). These groups will then be further divided into two subgroups according to the use of synbiotic or placebo capsules. Therefore, the study will consist of four groups in total. The sample size of the study was determined as 92 participants, with 23 participants included in each group.

All participants will receive non-surgical periodontal therapy (NSPT) at baseline. In addition to NSPT, participants will use either synbiotic or placebo capsules once daily for 90 days.

To evaluate clinical periodontal, immunological, and microbiological parameters, periodontal measurements will be performed, and saliva and subgingival plaque samples will be collected. In addition, stool samples will be collected from participants to evaluate the effects of synbiotic supplementation on the gastrointestinal microbiota, and microbiota analyses will be performed.

All samples will be collected again and evaluated at the third month following non-surgical periodontal therapy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Periodontitis is a chronic inflammatory disease characterized by the progressive destruction of tooth-supporting tissues, leading to periodontal pocket formation, bleeding on probing, clinical attachment loss, alveolar bone loss, and ultimately tooth loss if untreated. During disease progression, periodontal pathogens stimulate the production of proinflammatory mediators such as IL-1β and IL-8, which contribute to tissue destruction and immune cell recruitment. Excessive inflammatory responses increase reactive oxygen species (ROS) production, resulting in oxidative stress and oxidative DNA damage, commonly assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG).

Smoking is a major risk factor for periodontitis, as it alters the oral microbiota, impairs immune responses, and increases oxidative stress, often reducing the effectiveness of periodontal therapy. Although non-surgical periodontal therapy is the standard treatment for periodontitis, its outcomes may be limited in smokers and in severe cases.

Synbiotics, which combine probiotics and prebiotics, may help restore microbial balance, modulate host immune responses, and reduce oxidative stress. Therefore, adjunctive synbiotic supplementation alongside non-surgical periodontal therapy may enhance periodontal treatment outcomes, particularly in individuals with periodontitis.

There is limited evidence regarding the combined evaluation of the effects of synbiotic supplementation on clinical periodontal parameters, immunological markers, microbiological parameters, and microbiota in smokers with periodontitis. Therefore, the aim of this placebo-controlled, parallel-group, double-blind, prospective clinical study is to evaluate the effects of adjunctive synbiotic supplementation combined with non-surgical periodontal therapy on clinical periodontal parameters, IL-1β, IL-8, and 8-OHdG levels, periodontal pathogens, and gastrointestinal microbiota in smokers and non-smokers with generalized Stage III/IV Grade B/C periodontitis.

Following Ethics Committee approval, patients diagnosed with generalized Stage III-IV Grade B/C periodontitis, without systemic disease, who apply to the Department of Periodontology at Biruni University Faculty of Dentistry and voluntarily agree to participate in the study will be included.

Sample size analysis was performed based on the "short-term effect of probiotic capsules on probing pocket depth at the 3rd month" reported in the meta-analysis conducted by Ausenda et al. (2023).

At the determined alpha level, a total of 84 participants (21 participants per group) were required according to the two-sample t-test model to achieve 80% power with a two-sided test. Assuming a 10% dropout rate during the study period, the sample size was determined as 92 participants, and it was decided to include 23 patients per group.

All non-surgical periodontal treatments of the participating patients will be performed by a blinded investigator (İ.Ö.), while clinical parameter measurements will be performed by another calibrated blinded investigator (H.N.).

At baseline, clinical periodontal measurements (PI, BOP, PPD, CAL) will be recorded, and one day after the clinical measurements, saliva samples will be collected to evaluate immunological parameters (IL-1β, IL-8, 8-OHdG). On the same day, subgingival plaque samples will be collected to evaluate microbiological parameters, and stool samples will be collected from the patients in order to evaluate changes in the microbiota.

After the relevant forms are completed and the samples are collected, NSPT will be performed. The use of synbiotic supplement/placebo capsules will begin from the first treatment session. One placebo/synbiotic capsule (Bigflor) will be administered every evening for 90 days. At the 3rd month following treatment, periodontal measurements will be repeated, and saliva, subgingival plaque, and stool samples will be collected again.

Clinical Measurements

Before the periodontal clinical measurements begin, a calibration study will be performed to evaluate the consistency of the investigator. Within this scope, the investigator will perform periodontal clinical parameter measurements (PI, BOP, PPD, CAL) on 10 volunteer patients in two separate sessions (24 hours apart). Agreement between the measurements will be evaluated using intraclass correlation coefficient (ICC) analysis, and an ICC value above 0.80 will confirm sufficient reproducibility of the measurements. Accordingly, all periodontal evaluations will be performed by a single calibrated investigator (H.N.) at six sites per tooth (mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, and distolingual) using a periodontal probe with a diameter of 0.5 mm and a length of 15 mm (PCP-UNC 15, Hu-Friedy, USA).

Plaque Score (PS): PS measurements will be performed based on the presence (+) or absence (-) of plaque on tooth surfaces. Following evaluation of all sites, the plaque percentage for each patient will be calculated using the following formula:

Number of sites with plaque / Total number of sites × 100

Bleeding on Probing (BOP) (%): In order to determine the inflammatory condition of the pocket base and pocket epithelium, scoring will be performed as positive (+) or negative (-) depending on the presence or absence of bleeding in the sulcus 10 seconds after pocket depth measurement. The BOP index for each patient will be calculated as the percentage of bleeding on probing using the following equation:

Number of bleeding surfaces / Total number of tooth surfaces × 100

Probing Pocket Depth (PPD): Measurements will be performed at six sites of each tooth (mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, and distolingual). The periodontal probe will be inserted to the base of the pocket, and the distance between the pocket base and the free gingival margin will be measured.

Clinical Attachment Level (CAL) (mm): The distance from the cemento-enamel junction to the base of the pocket will be measured.

Gingival Margin Position (GMP): The distance between the cemento-enamel junction and the gingival margin will be measured in millimeters.

Collection of Saliva Samples:

Unstimulated saliva samples (1.5 ml) will be collected from the participants early in the morning into sterile tubes using a sterile glass funnel. Saliva collection will be performed one day after clinical periodontal measurements. Participants will rest for 5 minutes in a relaxed seated position with their heads slightly tilted forward and eyes open, allowing saliva to accumulate in the floor of the mouth, and they will be asked to spit into a sterile tube every 60 seconds for 5 minutes. Samples will be stored at -80°C.

Collection of Subgingival Plaque Samples:

Subgingival plaque samples will be collected at baseline from a total of four teeth, one tooth from each quadrant with the deepest probing pocket depth. Before sample collection, the relevant areas will be isolated with cotton rolls and gently dried with compressed air to prevent contamination. Two sterile paper points (one mesial and one distal) will be inserted into the pocket of each selected tooth until resistance is felt and left in place for 10 seconds. The paper points obtained from each tooth will be pooled and transferred into sterile Eppendorf tubes. All samples will be stored at -80°C until microbiological analysis.

Collection of Stool Samples:

Samples will be collected at home using sterile, disposable, leak-proof, and labeled stool collection containers provided to the participants in advance. Samples will be collected in a manner that prevents contact with urine or water in order to avoid contamination. Stool samples delivered to the clinic will be stored at -20°C until analysis.

Non-Surgical Periodontal Therapy

Procedures will be performed by a double-blinded, experienced, and standardized investigator according to the EFP S3 Level Clinical Practice Guideline published in 2021.

Re-evaluation

At the 3rd month following periodontal treatment, clinical parameters together with saliva, plaque, and stool samples of the participants will be re-evaluated.

Sample Analysis

For immunological analysis, salivary 8-OHdG, IL-1β, and IL-8 levels will be analyzed using ELISA tests in the biochemistry laboratory of the related company for a service fee.

For microbiological analysis, subgingival plaque and saliva samples will be transported on dry ice to the Department of Periodontology at KU Leuven, Belgium, and stored at -80°C upon arrival. DNA extraction will be performed according to the manufacturer's instructions.

For microbiota analysis, stool samples will be transported on dry ice to the Department of Periodontology at KU Leuven, Belgium, stored at -20°C upon arrival, and analyzed later. For microbiota analysis, total microbial DNA will be isolated from stool samples.

Study Type

Interventional

Enrollment (Estimated)

92

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age between 18 and 65 years
  • Diagnosis of generalized Stage III/IV Grade B/C periodontitis
  • Willingness to participate in the study and provide informed consent
  • No periodontal treatment within the last 3 months
  • No use of antibiotics or anti-inflammatory drugs within the last 3 months
  • Not being pregnant or breastfeeding
  • Presence of at least 20 teeth
  • Body mass index (BMI) between 18.5 and 30 kg/m²

Exclusion Criteria:

  • Failure to meet voluntary participation requirements
  • Presence of systemic diseases affecting the periodontium or immune response
  • Use of additional dietary supplements
  • Pregnancy or breastfeeding
  • Use of immunosuppressive medications Individuals who may have difficulty complying with the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SS (Smokers + Synbiotic)
Participants with generalized Stage III-IV Grade B/C periodontitis who smoke and receive synbiotic supplementation once daily for 90 days in addition to non-surgical periodontal therapy.
Dietary supplement: Synbiotic supplementation

Product Name: Bigflor Capsule Food Supplement Containing Probiotic Microorganisms Approval Number: 005400-08.02.2019 Manufacturer: Nuvita İlaç ve Kimya Sanayi Ticaret Anonim Şirketi Manufacturer Registration/Approval Number: TR-34-K-063184

Contents:

Saccharomyces boulardii (5×10⁹ cfu/day) - 250 mg Probiotic Blend (3.5×10⁹ cfu/day) (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium longum, Streptococcus thermophilus) - 22.5 mg Prebiotic (Inulin) - 25 mg
Placebo Comparator: SP (Smokers + Placebo)
Participants with generalized Stage III-IV Grade B/C periodontitis who smoke and receive placebo supplementation once daily for 90 days in addition to non-surgical periodontal therapy.
Other: Placebo Administration
The use of a placebo in the control group
Experimental: NS (Non-smokers + Synbiotic)
Non-smoking participants with generalized Stage III-IV Grade B/C periodontitis who receive synbiotic supplementation once daily for 90 days in addition to non-surgical periodontal therapy.
Dietary supplement: Synbiotic supplementation

Product Name: Bigflor Capsule Food Supplement Containing Probiotic Microorganisms Approval Number: 005400-08.02.2019 Manufacturer: Nuvita İlaç ve Kimya Sanayi Ticaret Anonim Şirketi Manufacturer Registration/Approval Number: TR-34-K-063184

Contents:

Saccharomyces boulardii (5×10⁹ cfu/day) - 250 mg Probiotic Blend (3.5×10⁹ cfu/day) (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium longum, Streptococcus thermophilus) - 22.5 mg Prebiotic (Inulin) - 25 mg
Placebo Comparator: NP (Non-smokers + Placebo)
Non-smoking participants with generalized Stage III-IV Grade B/C periodontitis who receive placebo supplementation once daily for 90 days in addition to non-surgical periodontal therapy.
Other: Placebo Administration
The use of a placebo in the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Probing Pocket Depth (PPD)
Time Frame: Baseline and 3 months after non-surgical periodontal therapy
Evaluation of changes in probing pocket depth following non-surgical periodontal therapy combined with synbiotic or placebo supplementation in smokers and non-smokers with generalized Stage III-IV Grade B/C periodontitis.
Baseline and 3 months after non-surgical periodontal therapy
Gain in Clinical Attachment Level (CAL)
Time Frame: Baseline and 3 months after non-surgical periodontal therapy
Evaluation of changes in clinical attachment level following non-surgical periodontal therapy combined with synbiotic or placebo supplementation in smokers and non-smokers with generalized Stage III-IV Grade B/C periodontitis.
Baseline and 3 months after non-surgical periodontal therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative Changes in Periodontal Pathogens
Time Frame: Baseline and 3 months after non-surgical periodontal therapy
Assessment of quantitative changes in periodontal pathogens in subgingival plaque samples following non-surgical periodontal therapy combined with synbiotic or placebo supplementation.
Baseline and 3 months after non-surgical periodontal therapy
Changes in IL-1β, IL-8, and 8-OHdG Levels
Time Frame: Baseline and 3 months after non-surgical periodontal therapy
Evaluation of changes in inflammatory and oxidative stress biomarkers, including IL-1β, IL-8, and 8-OHdG levels, following non-surgical periodontal therapy combined with synbiotic or placebo supplementation.
Baseline and 3 months after non-surgical periodontal therapy
Changes in Plaque Index
Time Frame: Baseline and 3 months after non-surgical periodontal therapy
Assessment of changes in plaque index values following non-surgical periodontal therapy combined with synbiotic or placebo supplementation.
Baseline and 3 months after non-surgical periodontal therapy
Changes in Bleeding on Probing
Time Frame: Baseline and 3 months after non-surgical periodontal therapy
Assessment of changes in bleeding on probing values following non-surgical periodontal therapy combined with synbiotic or placebo supplementation.
Baseline and 3 months after non-surgical periodontal therapy
Changes in Gastrointestinal Microbiota
Time Frame: Baseline and 3 months after non-surgical periodontal therapy
Evaluation of changes in gastrointestinal microbiota profiles using stool samples following non-surgical periodontal therapy combined with synbiotic or placebo supplementation.
Baseline and 3 months after non-surgical periodontal therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biruni University

Collaborators

KU Leuven

Investigators

  • Principal Investigator: Burcu Karaduman, Biruni University, Faculty of Dentistry, Department of Periodontology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 6, 2026

Primary Completion (Estimated)

July 6, 2027

Study Completion (Estimated)

October 6, 2027

Study Registration Dates

First Submitted

June 2, 2026

First Submitted That Met QC Criteria

June 24, 2026

First Posted (Actual)

June 26, 2026

Study Record Updates

Last Update Posted (Actual)

June 26, 2026

Last Update Submitted That Met QC Criteria

June 24, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-08

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data collected during the study will not be shared due to privacy and confidentiality considerations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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