AIMS: To determine the relationship between microbiome dysbiosis indices and biofilm immunogenicity and their prognostic implications on periodontal treatment response. MATERIALS AND METHODS: Thirty periodontally healthy controls and 30 periodontitis cases (stage III) were recruited. Cases received non-surgical periodontal therapy (NSPT), and their treatment response at 6 months was evaluated using a treat-to-target endpoint (</= 4 sites with probing depths >/= 5 mm). Pooled subgingival biofilm samples were obtained from controls and cases. The V3-4 hypervariable region of the 16S rRNA gene was sequenced and two compositional indices (subgingival microbiome dysbiosis index, SMDI, and dysbiosis ratio, DR) were calculated. Nuclear factor kappa-B (NF-kappaB) activation elicited by biofilm samples in monocytic reporter cells was quantified to assess biofilm immunogenicity. RESULTS: SMDI, DR and biofilm immunogenicity were highly diagnostic for periodontitis (area under curves [AUC] > 0.90, p < 0.001). Among periodontitis cases, all three microbial parameters were significantly reduced after NSPT (p < 0.001). Cases achieving the treat-to-target endpoint had lower pre-treatment SMDI and biofilm immunogenicity (p < 0.05) and different microbial recolonization patterns from poor responders. Both measures predicted treatment response (AUC of 0.767 and 0.835, respectively, p < 0.05). CONCLUSION: Subgingival biofilm dysbiosis quantified using SMDI and biofilm immunogenicity was diagnostic of periodontitis and predictive of NSPT outcomes.
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