Microbiological Modulation Of The Oral-Gut Axis After Treatment With Or Without Systemic Use Of Probiotics In Patients With Periodontitis: A Randomized Controlled Clinical Study.

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This study aims to evaluate whether the oral administration of probiotics, in combination with conventional periodontal treatment (deep cleaning of the tooth root surfaces), can improve oral health and influence the relationship between oral and gut bacteria in individuals with periodontitis.

The study will include adults aged 30 years or older diagnosed with advanced periodontitis and receiving treatment at the School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP). Individuals with systemic diseases that may interfere with the study outcomes, pregnant or breastfeeding women, smokers, recent former smokers, or individuals who have used antibiotics, probiotics, or certain medications within the previous six months will not be eligible to participate.

Participants will be randomly assigned to two groups: one group will receive conventional periodontal treatment alone, while the other will receive the same treatment combined with probiotic supplementation. Before and after treatment, periodontal health will be assessed, including the presence of dental plaque, bleeding, periodontal pocket depth, and clinical attachment levels. Inflammatory substances present in gingival fluid will also be analyzed to evaluate the response to treatment.

The findings of this study are expected to help clarify whether probiotics used as an adjunct to periodontal treatment can reduce inflammation and promote a more balanced relationship between oral and gut microorganisms, thereby contributing to improved periodontal health.

Periodontitis is a chronic inflammatory disease of multifactorial origin, characterized by the destruction of the tooth-supporting tissues as a result of the interaction between a dysbiotic biofilm and the host immunoinflammatory response. Recent evidence suggests that the oral microbiota may influence the gut microbiota through the oral-gut axis, contributing to local and systemic alterations. In this context, the use of probiotics as an adjunctive therapy to conventional periodontal treatment may favor the restoration of microbial balance and reduce inflammation.

The aim of this study is to evaluate the impact of systemic probiotic therapy, used as an adjunct to scaling and root planing (SRP), on the microbiological modulation of the oral-gut axis in patients with periodontitis. In addition, the effects of the intervention on periodontal clinical parameters, the immunoinflammatory profile, and the composition of the oral and gut microbiota will be investigated.

This randomized, placebo-controlled clinical trial will include 40 systemically healthy participants aged 30 years or older, diagnosed with generalized Stage III or IV, Grade B/C periodontitis, recruited at the School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP). Participants will be randomly allocated into two groups: one group will receive scaling and root planing associated with the probiotic Bifidobacterium animalis subsp. lactis HN019, whereas the other group will receive the same periodontal treatment associated with placebo. The probiotic or placebo will be administered orally at a dose of one capsule per day for 30 days.

Periodontal clinical parameters will be recorded, including plaque index, bleeding index, probing depth, bleeding on probing, and clinical attachment level. The immunoinflammatory profile will be evaluated by quantifying CCL19, IL-6, TNF-α, IL-1β, and IL-17 in gingival crevicular fluid using multiplex assays (Luminex). To investigate modulation of the oral-gut axis, subgingival biofilm and fecal samples will be collected before and after the intervention for analysis of the oral and gut microbiota.

The results will allow us to determine whether the systemic administration of Bifidobacterium animalis subsp. lactis HN019 enhances the effects of non-surgical periodontal therapy, promoting clinical, immunological, and microbiological improvements compared with placebo.

Inclusion Criteria:

• Systemically healthy individuals;
• Age of 30 years or older;
• Both genders;
• At least 15 teeth, excluding third molars and teeth indicated for extraction
• At least 30% of the teeth presenting probing depth (PD) and clinical attachment loss (CAL) greater than or equal to 5 mm;
• Individuals diagnosed with generalized Stage III or IV, Grade B or C periodontitis;
• Presence of at least 8 teeth with at least one non-contiguous interproximal site presenting probing depth (PD) and clinical attachment level (CAL) greater than or equal to 5 mm.

Exclusion Criteria:

• Current smokers or former smokers who quit within the past 5 years;
• Pregnant or breastfeeding women;
• History of periodontal treatment within the previous 6 months;
• Continuous use of oral antiseptics, systemic antibiotics, corticosteroids, nonsteroidal anti-inflammatory drugs, immunosuppressive agents, estrogen, selective estrogen receptor modulators, or medications that may affect bone metabolism (such as alendronate, calcitonin, and others) within the previous 6 months;
• Presence of systemic conditions that may alter the host response to periodontal treatment (such as diabetes, human papillomavirus infection, or Down syndrome) or that require antibiotic prophylaxis before dental treatment (such as mitral valve prolapse);
• Use of probiotics within the previous 6 months.