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

Condition(s) studied

Investigational drug(s) / intervention(s)

Non-surgical periodontal therapy (NSPT) and supportive periodontal therapy (SPT): Guideline-concordant non-surgical periodontal therapy including mechanical subgingival instrumentation and risk-factor-oriented oral hygiene instruction, followed by supportive periodontal therapy (maintenance) as part of routine care. No placebo is used.

Probiotic lozenge (Limosilactobacillus reuteri; GUM® PerioBalance®): Commercial dietary supplement lozenge containing Limosilactobacillus reuteri (GUM® PerioBalance®, Sunstar Deutschland GmbH, Schönau, Germany). Administered orally according to manufacturer instructions for 3 months starting with NSPT.

Vitamin B12 drops (natural elements): Commercial dietary supplement vitamin B12 drops (natural elements GmbH, Düsseldorf, Germany). Administered orally according to manufacturer instructions for 3 months, in addition to the probiotic regimen, starting with NSPT.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Change in oral microbiome composition (supragingival and subgingival) — Baseline through 12 months (assessed at baseline, NSPT instrumentation visit, ~3 months, ~6 months, and ~12 months).
  Changes in supragingival and subgingival microbial community structure and taxonomic profiles, assessed by 16S rDNA-based profiling and metagenomic sequencing (as applicable), including diversity metrics and relative abundance of microbial taxa/features.

Trial sites (1)

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