Adjunctive Gaseous Ozone Improves Clinical and Microbiological Outcomes in Periodontitis: A Randomized Split-Mouth Study

Background/Objectives: To evaluate the clinical and microbiological effects of adjunctive gaseous ozone therapy combined with full-mouth ultrasonic debridement and scaling and root planing (FMUD–SRP) in patients with generalized periodontitis. Materials and Methods: Thirty-nine patients with stage II–IV generalized periodontitis were enrolled in a randomized split-mouth clinical trial. Quadrants were assigned to receive FMUD–SRP alone or FMUD–SRP plus adjunctive gaseous ozone therapy. Ozone (2100 ppm, 80% oxygen) was applied subgingivally immediately after instrumentation during three treatment sessions. Clinical parameters were recorded at baseline, 45, and 90 days. Subgingival plaque samples were analyzed using qualitative polymerase chain reaction to detect six periodontal pathogens. Results: Both treatments resulted in significant clinical improvements over time (p < 0.05). At 90 days, ozone-treated sites showed greater probing pocket depth reduction (−1.6 ± 0.8 mm vs. −1.2 ± 0.8 mm; p = 0.02) and clinical attachment level gain (−1.1 ± 1.0 mm vs. −0.6 ± 1.0 mm; p = 0.03) compared with control sites. No significant intergroup differences were observed for bleeding on probing, plaque index, or gingival recession. A significantly greater reduction in the detection frequency of periodontal pathogens was observed in the ozone group, including complete suppression of Treponema denticola and marked reductions in other anaerobic species. Conclusions: Adjunctive gaseous ozone therapy enhances the clinical outcomes of non-surgical periodontal treatment and exerts a selective antimicrobial effect against anaerobic periodontal pathogens.