AbstractAimTo evaluate the effect of non‐surgical periodontal therapy (NSPT) on salivary histone deacetylases (HDACs) gene expression in patients with Stage III–IV periodontitis at baseline and at 3 and 6 months post NSPT treatment.Materials and MethodsTwenty patients completed the study. Periodontitis (as well as the corresponding staging and grading) was diagnosed according to the 2017 World Workshop Classification. Clinical measures were recorded and whole unstimulated saliva was collected at baseline and at 3 and 6 months after NSPT. The expression of 11 HDACs was determined using reverse‐transcription PCR, and the respective changes over time were evaluated.ResultsSix months after NSPT, significant improvements in all clinical periodontal parameters were observed, concomitant with significant up‐regulation of HDAC2, 4, 6, 8, 9 and 11 expressions. Subgroup analyses of non‐responders and responders revealed no significant differences in HDACs mRNA expression between groups at any time point.ConclusionsThis prospective clinical study identified longitudinal changes in salivary HDACs expression in response to NSPT, which provides new insights into the epigenetic mechanisms underlying the pathobiology of periodontitis and creates avenues for the discovery of novel biomarkers.