Toll-like receptor-4 activation by subgingival biofilm and periodontal treatment response

Objectives This study aims to investigate longitudinally the activation of Toll-like receptor-4 (TLR-4) by subgingival biofilm samples before and after nonsurgical periodontal therapy (NSPT). Materials and methods Forty periodontitis patients received NSPT and were reviewed 3 and 6 months post-treatment. Subgingival biofilm was sampled from 4 teeth per patient, at baseline and each follow-up time point. TLR-4 activation was determined using the HEK-BLUE™/hTLR4 system. Changes in TLR-4 activation and probing pocket depths (PPDs) were evaluated using generalised linear models, and the association between TLR-4 activation and pocket reduction (defined as 6-month PPDs ≤ 3mm) was determined using generalised estimating equations. Results At 6 months, the mean TLR-4 activation by subgingival biofilm samples was significantly reduced from 11.2AU (95%CI 7.1AU, 15.4AU) to 3.6AU (95%CI 2.3AU, 4.8AU, p < 0.001), paralleling significant reductions in mean PPDs at sampled sites. The response to NSPT was associated with longitudinal TLR-4 activation profiles, with significantly higher TLR-4 activation by subgingival biofilm obtained from sites that did not achieve pocket reduction, compared to sites at which pocket reduction was achieved. Conclusions The activation of TLR-4 by subgingival biofilm samples was reduced after NSPT, and this reduction was significantly associated with the clinical improvements (PPD reductions) at sampled sites. Clinical relevance This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.