About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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.
Disqualifiers
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.
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.
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.
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.
Trial design
Parallel
Treatments tested in this trial
Probiotic Blend Lozenge
Dietary supplementL. 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.
Placebo Lozenge
Dietary supplementDaily placebo lozenge.
Treatment groups
Trial outcomes
Primary outcomes
Matrix metalloproteinase-8 (MMP-8)in gingival crevicular fluid (GCF)
MMP-8 is a validated biomarker of periodontal collagen breakdown
Secondary outcomes
C-reactive protein (CRP) in saliva and plasma
CRP is an acute phase protein used as marker of oral and systemic inflammation
Interleukin 1β (IL-1β) in saliva and plasma
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
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
IL-8 is a chemokine involved in neutrophil recruitment and local inflammatory activity, measured as a marker of periodontal inflammatory response.
Locations
Sponsors and contacts
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