Clinical Research Directory

Characterization of Small Intestinal Bacterial Overgrowth and Intestinal Barrier-Related Biomarkers in Patients With Severe Periodontitis: A Pilot Prospective Longitudinal Observational Cohort Study

Periodontitis is a chronic inflammatory disease characterized by dysbiotic subgingival biofilms, inflammation, and progressive destruction of the tooth-supporting tissues. Beyond the local periodontal lesion, periodontal inflammation may contribute to systemic inflammatory burden through the dissemination of microbial products and inflammatory mediators. The oral cavity and intestinal tract are closely connected through continuous microbial exposure, swallowing of oral microorganisms, host immune pathways, and systemic circulation. Emerging evidence suggests that periodontal inflammation may be associated with alterations of the intestinal microbial environment and gut barrier function. However, the human evidence remains heterogeneous and does not currently establish a causal relationship between periodontitis and intestinal dysbiosis or small intestinal bacterial overgrowth (SIBO). SIBO represents an abnormal increase and/or alteration of bacterial populations in the small intestine and may be associated with gastrointestinal symptoms and intestinal microbial imbalance. The occurrence of SIBO in patients with advanced periodontitis has not been adequately characterized. Consequently, determining how frequently SIBO is detected in a clinically well-characterized cohort of participants with Stage III periodontitis may provide useful exploratory data and may support future controlled studies. Alterations in the intestinal microbial environment may be accompanied by changes in intestinal barrier function and increased systemic exposure to bacterial products. Zonulin has been investigated as a biomarker related to intestinal barrier regulation, while lipopolysaccharide-binding protein (LBP), or another prespecified bacterial-exposure marker depending on the finalized laboratory assay, may provide information regarding systemic exposure to bacterial products. These biomarkers should be interpreted as indirect biological indicators rather than as direct measurements of intestinal permeability. The present study therefore approaches the oral-gut-systemic interface from an exploratory clinical perspective. It does not aim to demonstrate that periodontitis causes SIBO. Instead, it seeks to characterize the occurrence of SIBO in participants with severe periodontitis and to explore whether SIBO is accompanied by alterations in intestinal barrier-related biomarkers and systemic exposure to bacterial products. The longitudinal component will further examine whether improvement in periodontal clinical status following routine, clinically indicated periodontal therapy is accompanied by changes in SIBO status and these biological markers.

A Clinical Trial Comparing 2x/Day for 30-minutes Use of the Emanate Perio PODS Post-SRP to a Control Group Post-SRP.

The goal of this clinical trial is to compare safety and to see if individuals with generalized stage III periodontitis that are given a periodontal hydrogel dressing on a wound healing after plaque and tartar have been removed from teeth have greater healing than individuals who are given no treatment after.

Evaluation of the Effect of Smoking on Apelin, Periostin, and High-Sensitivity CRP Levels in Gingival Crevicular Fluid and Serum

Periodontal health is influenced by various local and systemic factors, with smoking being one of the major environmental risk factors. This clinical study is designed to investigate the biochemical profiles of individuals by measuring apelin, periostin, and high-sensitivity C-reactive protein (hs-CRP) levels in both gingival crevicular fluid and serum. The participants will be divided into specific study groups based on their smoking status and periodontal condition. Samples of gingival crevicular fluid and serum will be collected under standard clinical protocols, and biomarker concentrations will be analyzed quantitatively using the ELISA (Enzyme-Linked Immunosorbent Assay) method to evaluate their potential correlation with periodontal status.

Er,Cr:YSGG Laser in Smokers With Stage III Periodontitis

Periodontitis is an inflammatory disease that affects the tissues supporting the teeth. If the disease progresses, it can cause loss of the tissues and bone around the teeth and lead to the formation of deep spaces, called periodontal pockets, between the teeth and gums. The main treatment for periodontitis is to improve oral hygiene and remove bacterial deposits and calculus from the tooth and root surfaces. Smoking is an important risk factor for periodontitis and may reduce the response to periodontal treatment by negatively affecting tissue healing. For this reason, additional treatments that may improve healing in smokers are being investigated. One of these approaches is the use of dental lasers together with conventional nonsurgical periodontal treatment. The purpose of this study is to investigate whether adding Er,Cr:YSGG laser treatment to nonsurgical periodontal therapy improves treatment outcomes in systemically healthy smokers with Stage III periodontitis. This study will use a split-mouth design, meaning that two different treatments will be compared within the same participant. One side of the mouth will receive conventional nonsurgical periodontal treatment, including scaling and root surface instrumentation. The other side will receive the same treatment together with Er,Cr:YSGG laser application. Changes in gum health, periodontal pocket depth, bone-related findings on radiographs, and biological markers related to bone metabolism will be evaluated during follow-up. The study hypothesis is that adding Er,Cr:YSGG laser treatment to conventional nonsurgical periodontal therapy will provide additional clinical, radiographic, and biochemical benefits compared with conventional nonsurgical periodontal therapy alone in smokers with Stage III periodontitis.

Dental Loupe Versus Dental Operating Microscope for Non-Surgical Periodontal Treatment

Periodontitis is a multifactorial, non-infectious disease that can lead to tooth loss if left untreated. Advanced stages of periodontitis can affect chewing ability, nutritional status, and quality of life. Calculus removal, root planing, and mechanical removal of plaque should be considered a fundamental part of initial periodontal treatment. Furthermore, patients who undergo calculus removal and root planing followed by regular maintenance programs experience less tooth loss and clinical attachment loss. Calculus removal and root planing are integral parts of non-surgical periodontal treatment to remove bacterial plaque and calculus from diseased root surfaces. The use of magnification systems to increase the field of view in both surgical and non-surgical procedures dates back to the 1860s with the first use of surgical microscopes. Magnification systems were first used in dentistry in the first half of the 20th century. In 1978, Apotheker and Jako developed the first surgical microscope for use in dentistry. The use of magnifying loupes as visual aids by dentists has become increasingly popular over the years, with continuous improvements in design and effectiveness. A 2019 survey among dentists indicated that magnifying lenses are one of the significant technological advancements in this profession. Periodontal endoscopy is also one of the approaches clinicians use to improve visibility. Dental magnification systems are known to increase effectiveness, especially in interproximal areas where access and visibility are limited. Clinical studies have compared root surface planing procedures performed with periodontal endoscopy with traditional root surface planing. The results of the studies showed a significant difference in clinical outcomes in patients treated with periodontal endoscopy compared to those treated with traditional methods. The aim of this study is to analyze the clinical and microbiological benefits of image magnification systems (dental loupe and dental microscope) in scaling and root surface planing in the treatment of patients with periodontitis.

Effect of Guided Biofilm Therapy in Patients With Stage 3 Periodontitis

This randomized interventional study aims to compare the clinical and biochemical effects of conventional non-surgical periodontal therapy (NSPT), adjunctive diode laser therapy, and guided biofilm therapy (GBT) in patients with Stage 3 periodontitis. Participants are allocated to one of three treatment groups: conventional NSPT alone, NSPT combined with diode laser therapy, or NSPT combined with guided biofilm therapy. Clinical periodontal parameters, including plaque index, gingival index, probing pocket depth, clinical attachment level, and bleeding on probing, are evaluated before treatment and during follow-up. In addition, serum and gingival crevicular fluid samples are collected to determine the levels of inflammatory biomarkers, including IL-1β, IL-1 receptor antagonist (IL-1RA), sclerostin, and transforming growth factor-beta 1 (TGF-β1). The study evaluates whether adjunctive treatment modalities provide additional clinical and biological benefits compared with conventional non-surgical periodontal therapy alone.

Morphological Characteristics of Mandibular Molar Furcation Involvement and Efficacy of Regenerative Surgical Treatment

This study consists of two components evaluating furcation involvement in mandibular molars among Stage III or Stage IV periodontitis patients. Component 1 is a cross-sectional study evaluating the prevalence and morphological characteristics of Hamp Class II furcation defects during initial screening. Component 2 is a randomized controlled clinical trial in 30 selected patients comparing the diagnostic accuracy of Cone Beam Computed Tomography (CBCT) against direct intra-operative clinical measurements, as well as evaluating the clinical and radiographic outcomes of regenerative periodontal surgery using Acellular Dermal Matrix (ADM) + Enamel Matrix Derivative (EMD) + Xenograft versus Autogenous Connective Tissue Graft (CTG) + EMD + Xenograft.

Salivary TNF-α, FoxO-1, and SIRT-1 Levels in Periodontitis and Smoking

This study examines whether smoking and gum disease (periodontitis) are linked to changes in three biological markers found in saliva: TNF-α, FoxO-1, and SIRT-1. These markers are involved in inflammation and the body's response to stress. Eighty adults took part in the study, divided into four groups: healthy non-smokers, non-smokers with Stage III periodontitis (an advanced form of gum disease), healthy smokers, and smokers with Stage III periodontitis. Each participant had a dental examination and provided a saliva sample, which was analyzed in the laboratory to measure the levels of these three markers. The goal of the study is to better understand how smoking and gum disease together affect the body's inflammatory and stress-response pathways, which may help guide future approaches to prevention and treatment.

Minimally Invasive Non-Surgical Periodontal Treatment

This single-center, split-mouth, randomized controlled clinical trial aims to evaluate the clinical effectiveness of Minimally Invasive Non-Surgical Therapy (MINST) as an adjunct to conventional non-surgical periodontal therapy in patients with Stage III/IV periodontitis. Twenty-three systemically healthy adults presenting with bilateral molar teeth exhibiting periodontal pockets ≥5 mm with bleeding on probing will be enrolled. In each participant, molar teeth will be randomly allocated to receive either conventional subgingival scaling and root planing (SRP) using ultrasonic instruments alone (control) or conventional SRP followed by MINST using Mini-Five Gracey curettes under magnification loupes (test). Clinical periodontal parameters, including Plaque Index (PI), Gingival Index (GI), Bleeding on Probing (BOP), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL), will be evaluated at baseline, 3 months, and 6 months after treatment. The study will investigate whether MINST provides superior clinical outcomes compared with conventional non-surgical periodontal therapy.

Evaluation of Hyaluronic Acid and Chlorhexidine Gel as an Adjunct to Minimally Invasive Non-surgical Therapy in the Treatment of Stage III and IV Periodontitis

Stage III and IV periodontitis are advanced forms of periodontal disease characterized by significant attachment loss, deep periodontal pockets, and progressive destruction of supporting periodontal tissues. Minimally invasive non-surgical therapy (MINST) has been proposed as an effective treatment approach aimed at minimizing tissue trauma while achieving optimal biofilm and calculus removal. Adjunctive therapies may further enhance clinical outcomes by promoting wound healing and reducing inflammation. This randomized clinical trial aims to evaluate the effectiveness of a hyaluronic acid and chlorhexidine gel (Periofix Plus Gel) used as an adjunct to MINST in patients with Stage III and IV periodontitis. Participants will be randomly assigned to receive either MINST alone or MINST combined with local application of the hyaluronic acid/chlorhexidine gel. Clinical periodontal parameters, including probing pocket depth, clinical attachment level, bleeding on probing, and plaque-related indices, will be assessed at baseline and follow-up visits to determine whether adjunctive gel application provides additional clinical benefits compared with MINST alone. The study hypothesis is that the adjunctive use of hyaluronic acid and chlorhexidine gel following MINST will result in greater periodontal pocket reduction, improved clinical attachment gain, and enhanced soft tissue healing compared with MINST alone.

Omega-3 Plus Low-Dose Aspirin in Smokers With Stage III Periodontitis

This randomized double-blind placebo-controlled clinical trial aims to evaluate the clinical and biochemical effects of omega-3 fatty acids combined with low-dose aspirin as an adjunct to scaling and root planing (SRP) in smoker patients with Stage III periodontitis. The study compares test and control groups regarding periodontal clinical parameters and gingival crevicular fluid interleukin-1 beta (IL-1β) levels Or other inflammatory markers that will be determined later at baseline, 3 months, and 6 months following treatment

Hydrolyzed Collagen As A Host Modulation Agent in Non-Surgical Periodontal Treatment

This study was planned on the basis of the hypothesis that 'food supplements containing collagen will support the clinical effectiveness of non-surgical periodontal therapy'. In this context, the aim of the study is to investigate the therapeutic efficacy of collagen-containing food supplement as a host modulation agent in the non-surgical periodontal treatment of individuals with stage 3-4 periodontitis in a clinical and biochemical manner in a comprehensive manner. Initial day: Anamnesis, diagnosis and index measurements 2 days later, collection of serum samples from the patient, oral hygiene training and straightening of the whole mouth root surface and cleaning of the whole mouth tooth surface The next day, full mouth scalling and root planing are closed with the second session and tablets are started. End of 2nd month: Periodontal index measurement and oral hygiene training Collecting serum and tissue samples 2 days later End of 6th month Periodontal index measurement and oral hygiene training Collecting serum and tissue samples 2 days later

Influence of Re-evaluation Timing After Phase I Periodontal Therapy on Clinical and Periodontal Outcomes.

Periodontal disease remains a highly prevalent chronic inflammatory condition affecting the supporting structures of the teeth and is a leading cause of tooth loss worldwide. Contemporary periodontal therapy is structured into sequential phases, with non-surgical periodontal therapy (NSPT) forming the cornerstone of initial management. Following this phase, re-evaluation of periodontal status is critical to determine treatment outcomes and guide further intervention, including surgical therapy if required (1,2). Re-evaluation phase serves multiple purposes: it allows assessment of tissue response to therapy, measurement of reductions in probing pocket depth (PPD), gains in clinical attachment level (CAL), and evaluation of patient compliance with oral hygiene practices. It also aids in identifying residual pockets or persistent inflammation that may necessitate additional treatment (1,3). Despite its clinical importance, the optimal timing of re-evaluation remains inconsistently defined in the literature (1). Generally, current literature utilizes a timing frame from 1-3 months; up to 9 months (3,4). Current clinical guidelines, including those from the European Federation of Periodontology (EFP), generally recommend assessing whether the end points have been achieved; no periodontal pockets ≥ 5mm with bleeding on probing and no pocket ≥ 6mm (5). Emerging evidence suggests that certain clinical improvements, particularly reductions in inflammation and bleeding on probing (BOP), may occur as early as 4 weeks following therapy, raising questions about whether earlier re-evaluation could be clinically beneficial (2,3). Early reassessment may allow for more timely identification of non-responding sites, enabling prompt intervention and potentially improving overall treatment outcomes. Conversely, other studies indicate that full periodontal healing and maturation of tissues may require longer periods, supporting delayed re-evaluation intervals (1,2,3). Furthermore, patient-related factors such as systemic health, smoking status, and baseline disease severity may influence healing dynamics and thus the appropriate timing for reassessment (1). The heterogeneity of these factors highlights the potential need for a more individualized approach to re-evaluation rather than a fixed universal timeframe. Despite these considerations, there is a notable lack of high-quality comparative studies directly evaluating short-term versus conventional re-evaluation intervals following NSPT. Most available studies focus on treatment outcomes rather than the timing of reassessment itself. This creates a significant gap in the literature, particularly regarding whether earlier re-evaluation could enhance clinical decision-making, improve patient outcomes, or optimize resource utilization in clinical practice. In addition, with increasing emphasis on minimally invasive and patient-centered care, there is a growing need to refine periodontal treatment protocols to ensure efficiency without compromising effectiveness. Determining the optimal timing of re-evaluation could contribute to improved treatment planning, reduced disease progression, and enhanced long-term periodontal stability. Therefore, this study aims to address this gap by investigating the effectiveness and clinical implications of shorter re-evaluation intervals following periodontal therapy, compared to conventional timeframes.

Bone Substitutes and NIPSA in Intrabony Periodontal Defects: A Randomized Controlled Trial

This multicenter randomized controlled clinical trial aims to compare the clinical, radiographic, microbiological and molecular outcomes of two collagenated xenogeneic bone substitutes (GTO® and GenOs®) used in combination with the Non-Incised Papilla Surgical Approach (NIPSA) for the treatment of intrabony periodontal defects. The study will evaluate whether differences exist between the two biomaterials with respect to clinical attachment gain, defect resolution, wound healing and biological markers of regeneration.

Effects of Non-Surgical Periodontal Treatment on Inflammatory and Bone Markers in Periodontitis Patients

The goal of this study is to learn how a standard treatment called Scaling and Root Planing (SRP) affects specific biochemical markers in people with advanced gum disease (periodontitis). Periodontitis is a chronic condition that can lead to tooth loss. The main focus is to investigate a marker called Glycoprotein Non-Metastatic B (GPNMB). This is the first study to examine GPNMB levels in both the serum and the gingival crevicular fluid of people with this condition. The study aims to answer these main questions: How do GPNMB levels change after the Scaling and Root Planing treatment? How does GPNMB relate to other markers that control bone health and healing, such as TGF-β1, RANKL, and Osteoprotegerin? Researchers will compare 28 participants with advanced gum disease (Stage III Grade B/C) to 28 participants with healthy gums to see how these markers differ. Participants in the gum disease group will: Provide samples for laboratory analysis at the start of the study. Receive the standard mechanical treatment of their teeth and roots (Scaling and Root Planing). Return for follow-up visits 6 weeks and 3 months after treatment to provide new samples and have their gum health checked.

Application of a Fasting-mimicking Diet in Obese Patients With Periodontitis Stage III-IV

This study will evaluate whether a fasting-mimicking diet (FMD) can improve the systemic and periodontal response to non-surgical periodontal treatment in obese adults with severe periodontitis. Periodontitis is a serious inflammatory disease that damages the tissues supporting the teeth and may also contribute to inflammation elsewhere in the body. Obesity is also associated with increased systemic inflammation, which may worsen periodontal disease and affect treatment outcomes. In this pilot randomized cross-over clinical trial, eligible participants will receive full-mouth non-surgical periodontal therapy and will be assigned either to an FMD group or to a control group continuing their usual diet. The FMD will be administered in three 5-day cycles around the periodontal treatment period. After a wash-out period, the groups will switch interventions. The study will assess whether FMD can reduce systemic inflammation, measured primarily by serum C-reactive protein (CRP), and improve periodontal healing after treatment. Additional outcomes include clinical periodontal measurements, inflammatory markers in gingival crevicular fluid, and changes in oral and gut microbiota. Findings from this study will help determine the feasibility of this dietary approach and provide preliminary data for a larger clinical trial.

Non-surgical Periodontitis Treatment With Aspirin and Omega-3

The goal of this clinical trial is to learn if non-surgical periodontal treatment combined with Omega-3 fatty acids and Aspirin can improve clinical outcomes and biochemical markers in patients with periodontitis. The main questions it aims to answer are: Does the combination of Omega-3 and low-dose Aspirin significantly change the concentration of biochemical and immunological markers such as Interleukin-6 (IL-6) and C-reactive protein (CRP) in serum? Is the combination of Omega-3 and Aspirin more effective than Omega-3 alone or standard non-surgical treatment in treating periodontitis? Researchers will compare three groups: Control group: Scaling and root planing (SRP) only. Intervention group 1: SRP combined with Omega-3 fatty acids. Intervention group 2: SRP combined with Omega-3 fatty acids and 81mg Aspirin. The comparison aims to see if the combined therapy (Intervention group 2) provides superior anti-inflammatory effects and better clinical healing compared to the other groups. Participants will: Undergo clinical screening and selection based on study criteria. Be randomly assigned to one of the three treatment arms. Receive non-surgical periodontal treatment (scaling and root planing). Take prescribed supplements (Omega-3 or Omega-3 combined with 81mg Aspirin) according to their assigned group. Provide blood samples to measure changes in biochemical markers (IL-6, CRP).

Efficacy of Locally Delivered Rosemary Extract Gel in Management of Periodontitis

Rosemary extract is known for its antibacterial, anti-inflammatory and anti-oxidant properties that make it a promising therapeutic aid as a local delivery drug in deep periodontal pockets in adjunct to non-surgical periodontal therapy in management of periodontitis. These properties are due to the high content of phenolic compounds such as carnosic acid, urolic acid, rosmarinic acid or chlorogenic acid. Rosemary extract was previously investigated and proved its effectiveness against periodontopathogens in-vitro. Thus, its selected for this study to be administered in a gel form to assess its efficacy in management of periodontitis.

Periodontal Dressings in Non-Surgical Therapy

This study aims to evaluate and compare the efficacy of two different eugenol-free periodontal dressing materials-Ora-Aid (a hydrophilic polymer) and Coe-Pak (a zinc oxide-based paste)-following non-surgical periodontal treatment (scaling and root planing, SRP) in patients with Stage 3, Grade A periodontitis. The study utilizes a split-mouth design to analyze clinical periodontal parameters, patient comfort, and microbiological changes over a 3-month period.

Microbiological and Clinical Effects of Pre- and Probiotics in Non-Surgical Periodontal Therapy

Periodontitis is a prevalent chronic inflammatory disease driven by a dysbiotic oral biofilm and a dysregulated host immune response. Standard non-surgical periodontal therapy (NSPT) is primarily mechanical and, in selected cases, may be accompanied by antiseptics or systemic antibiotics. Targeted modulation of the oral microbiome ("microbiome engineering") is currently not part of routine periodontal care due to limited high-quality evidence. PROPARO is a single-center, randomized, controlled pilot study designed to assess whether adjunctive oral supplementation with a probiotic containing Limosilactobacillus reuteri (commercial dietary supplement lozenge) alone or combined with vitamin B12 (commercial dietary supplement drops) is associated with changes in supragingival and subgingival oral microbiome composition during guideline-concordant NSPT compared with standard care alone. Participants with Stage III or IV periodontitis will be randomized 1:1:1 to: (1) NSPT/SPT without supplementation (control), (2) NSPT/SPT plus probiotic lozenges for 3 months, or (3) NSPT/SPT plus probiotic lozenges and vitamin B12 drops for 3 months. The primary outcome is change in oral microbiome composition and structure (supragingival and subgingival), assessed using 16S rDNA-based profiling and metagenomic sequencing approaches. Secondary outcomes include clinical periodontal parameters (e.g., probing depth, clinical attachment level, bleeding on probing), oral hygiene/gingival indices, dental status, and participant-level ecological covariates (diet quality, perceived stress, physical activity). Sampling and assessments are aligned with routine care time points from baseline through supportive periodontal therapy follow-up (up to 12 months). This pilot trial aims to generate feasibility and effect-size estimates to inform future confirmatory studies and potential translation into guideline-based periodontal care.

3-Month Clinical Trial of Liquid S-PRF in Periodontal Debridement for Periodontitis Stages II-IV

What is the purpose of this study? This study is to investigate the effect of a processed blood product in healing after treatment for gum disease. In addition to scaling \& root debridement (deep cleaning) that is the standard treatment for periodontitis, this study will test the effectiveness of patient's processed blood in improving healing of diseased gums. What are the procedures to be followed? First, all patients will undergo dental check-up and X-ray imaging for suitability as a participant for the project. For participants who are eligible and included into study, upper \& lower jaws models will be made, and each will be given oral care kit \& instructions. The next appointment will be given for scaling \& root debridement with local numbing agent in one day. Towards the end of the treatment, a small amount (20 mℓ) of blood will be collected and spun to produce liquid platelet-rich fibrin that is then used to flush the treated gum pockets in half of the mouth. For the treated gum pockets in the opposite half of the mouth, sterile salt water (saline) will be used instead for comparison. Then, follow-up appointments are at monthly intervals until 3 months. Who should enter the study? Symptoms of gum disease include bleeding and/or receding gums, tooth/teeth appearing longer or feeling shaky/loose/weak, formation of large amount of calculus and/or black/empty space between teeth, frequent/recurrent gum swelling/pus, and/or bad breath.

Evaluation of The Periodontal Parameters Following Non-Surgical Periodontal Therapy With and Without Adjunctive Use of Injectable Platelet Rich Fibrin: A Randomized Controlled Clinical Trial

This randomized controlled clinical trial aims to evaluate the effectiveness of non-surgical periodontal therapy (NSPT) with and without the adjunctive use of injectable platelet-rich fibrin (I-PRF) in patients with chronic periodontitis. The primary objective is to assess changes in key periodontal parameters including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI) over a defined follow-up period. Participants will be randomly assigned to two groups: one receiving standard NSPT alone and the other receiving NSPT combined with subgingival application of I-PRF. The study seeks to determine whether the adjunctive use of I-PRF can enhance periodontal healing and improve clinical outcomes compared to conventional therapy alone.

Comparative Analysis of Gremlin-1, Syndecan-4 and IL-1 Beta Levels in Gingival Crevicular Fluid Among İndividuals With Periodontal Health and Stage III Periodontitis, Considering Both Smokers and Non-Smokers, Before and After Non-Surgical Periodontal Therapy

eriodontitis is a complex disease characterized by the inflammation and destruction of the tissues supporting the teeth, and smoking can adversely affect the pathophysiological changes in this process. In an unhealthy periodontium, the host's inflammatory response products can be detected in the content of DOS, and the presence of these components is crucial in obtaining information about the pathogenesis of periodontal disease. Biochemical markers found in DOS are significantly helpful in determining the active stages and regions of the disease and in evaluating the host response to periodontal treatment. IL-1β has been determined to play a leading role in the pathogenic mechanism of periodontal tissue destruction, and the degree of inflammation in the tissues can be measured by IL-1β activity in DOS. Syndecan-4, a member of the transmembrane heparan sulfate proteoglycan family, regulates cellular activities such as tissue homeostasis, inflammation, fibrosis, and tumor metastasis. Gremlin-1 is a protein that inhibits BMP (Bone Morphogenetic Protein) signaling, influencing cell growth and tissue development. Gremlin-1 plays an important role in tissue repair and regeneration, modulating inflammatory processes and regulating cellular homeostasis. While recent studies have explained the role of Syndecan-4 and Gremlin-1 in inflammation, their effects on periodontal tissues are still quite limited in the literature. Our study aims to investigate the effects of smoking on these biomarkers by comparing the periodontal status before and after treatment of healthy, smoking, and non-smoking individuals with stage 3 periodontitis, with the goal of developing early diagnostic tools in the future.