Periodontal Disease
Conditions
Keywords
Periodontal disease, Probiotic, Microbiome
Brief summary
Probiotics are live microorganisms that can be taken as supplements and have shown promise in playing a beneficial role in improving clinical conditions that are characterized by chronic inflammation, such as periodontal disease (PD). The human gut microbiome is composed of trillions of bacteria that reside throughout the gastrointestinal tract and has an important role in the modulation of inflammatory responses in the human host. There is evidence that PD is associated with alterations in the oral and gut microbiomes, suggesting that probiotics may reduce inflammation through microbiome modulation. However, individual responses to probiotics can be highly variable, and robust predictors of probiotic responsiveness remain poorly defined. There is also limited knowledge about how the oral and gut microbiome interact even though there is growing evidence for a bidirectional oral-gut axis with implications for host immunity, inflammation, and probiotic responsiveness. The overarching goal of this project is to identify oral and gut microbiome features that predict responsiveness to probiotic interventions as an adjuvant treatment for PD. We will conduct a double-blind randomized controlled trial in which New Hampshire adults with stage III PD will be randomized to receive a 12-week adjuvant intervention of either a daily probiotic (n=45) or placebo (n=45) lozenge. The probiotic intervention will consist of a once daily lozenge containing a standard dose of 200 million CFU of two strains of Limosilactobacillus reuteri (DSM 17938 and ATCC PTA 5289), a commercial formulation demonstrated to be safe and well-tolerated in this population over this treatment length. The primary outcome to quantify responsiveness to the probiotic as an adjuvant therapeutic for PD will be within-subject change from baseline in inflammatory markers, and oral and gut microbiome composition.
Interventions
DIETARY_SUPPLEMENTProbiotic Blend Lozenge
L. reuteri is a probiotic that has been shown to inhibit the activity of "red complex" species and reduce PD severity in vitro and in animal models, and has been shown to ameliorate clinical outcomes of PD in human trials.
DIETARY_SUPPLEMENTPlacebo Lozenge
Daily placebo lozenge.
Sponsors
University of New Hampshire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 45 and 65 years: Restricting eligibility to this age range reduces potential confounding from age-related comorbidities and ensures adequate natural dentition for standardized gingival crevicular fluid (GCF) sampling. 2. Diagnosis of Stage III periodontal disease (PD): Participants must have clinically confirmed Stage III (severe) PD according to the 2017 American Academy of Periodontology/European Federation of Periodontology (AAP/EFP) classification system to ensure consistent disease severity among enrolled participants.
Exclusion criteria
1. Use of prebiotic, probiotic, or fiber supplements within the previous 6 months: Recent use of microbiome-modulating supplements could alter baseline oral or gut microbial composition and confound assessment of responsiveness to the probiotic intervention. 2. Use of antibiotics within the previous 6 months: Antibiotic exposure can cause sustained disruptions to host microbiomes and immune responses, which may confound evaluation of probiotic-related changes in inflammatory and microbial outcomes. 3. Systemic diseases affecting the periodontium (uncontrolled diabetes mellitus defined as HbA1c ≥8%, autoimmune diseases): These conditions may independently influence periodontal inflammation, immune responses, and microbiome composition, potentially confounding interpretation of study outcomes. 4. History of communicable or chronic diseases that may render study participation unsafe: Certain medical conditions may increase the risk of adverse events associated with study procedures or probiotic exposure. 5. Pregnancy or breastfeeding: Physiological changes during pregnancy and lactation may influence periodontal status, immune function, and microbiome composition. 6. Having fewer than 20 natural teeth: Adequate natural dentition is required to support standardized periodontal assessments and reliable biospecimen collection. 7. Use of removable dentures: Denture use alters the oral microbiome and local inflammatory environment and may compromise the validity of periodontal outcome measures. 8. Surgical periodontal disease treatment within the previous 6 months: Recent surgical intervention may induce substantial changes in the periodontal environment, complicating baseline measurement and interpretation of treatment response. 9. Ongoing participation in another clinical trial: Concurrent participation in another trial may introduce overlapping interventions or behavioral changes that could compromise internal validity. 10. Lack of mobility or physical independence: Physical limitations may make participation burdensome or interfere with attendance at study visits and completion of study procedures. 11. Inability to communicate orally or in written English: Because study procedures and consent materials will be conducted in English, adequate language proficiency is required to ensure participants understand study instructions and provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Matrix metalloproteinase-8 (MMP-8)in gingival crevicular fluid (GCF) | Change from baseline to week 12 | MMP-8 is a validated biomarker of periodontal collagen breakdown |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C-reactive protein (CRP) in saliva and plasma | Change from baseline to week 12 | CRP is an acute phase protein used as marker of oral and systemic inflammation |
| Interleukin 1β (IL-1β) in saliva and plasma | Change from baseline to week 12 | Interleukin IL-1β is a pro-inflammatory cytokine measured in saliva and plasma as an indicator of systemic and oral inflammatory response. |
| IL-6 in saliva and plasma | Change from baseline to week 12 | Il-6 is a pro-inflammatory cytokine measured in saliva and plasma as an indicator of systemic and oral inflammatory response. |
| IL-8 in saliva and plasma | Change from baseline to week 12 | IL-8 is a chemokine involved in neutrophil recruitment and local inflammatory activity, measured as a marker of periodontal inflammatory response. |
| Tumor necrosis factor-alpha (TNF-α) in saliva and plasma | Change from baseline to week 12 | TNF-α is a pro-inflammatory cytokine associated with tissue inflammation and periodontal disease activity, measured to assess inflammatory modulation following probiotic supplementation. |
| Oral microbiome composition | Change from baseline to week 12 | Relative abundance and diversity of bacterial taxa in oral samples, assessed to determine whether probiotic supplementation alters the microbial community associated with periodontal disease. |
| Gut microbiome composition | Change from baseline to week 12 | Relative abundance and diversity of bacterial taxa in stool samples, assessed to evaluate whether probiotic supplementation affects gut microbial ecology. |
| Oral and gut microbiome functional potential | Change from baseline to week 12 | Predicted or measured microbial gene pathway profiles, assessed to identify functional microbial features associated with inflammatory response and probiotic responsiveness. |
Contacts
CONTACTMaria C Dao, PhD
CONTACTFrancesca Schembri, MS
Outcome results
None listed