Pattern analysis of the salivary metabolic profile has been proven accurate in discriminating between generalized periodontitis (GP) patients and healthy individuals (HI), as this disease modifies the salivary concentrations of specific metabolites. Due to the scarcity of data from previous studies, this study aimed to evaluate if non-surgical periodontal therapy (NST) could affect the metabolomic profile in GP patients’ saliva and if it compares to that of HI. Unstimulated salivary samples were collected from 11 HI and 12 GP patients before and 3 months after NST. Nuclear Magnetic Resonance (NMR) spectroscopy, followed by a supervised multivariate statistical approach on entire saliva spectra and partial least square (PLS) discriminant analysis, were performed to obtain metabolic profiles. In the GP group, periodontal treatment improved all clinical parameters, but not all the diseased sites were eradicated. PLS revealed an accuracy of 100% in distinguishing between metabolic profiles of GP patients before and after NST. Orthogonal projection to latent structure was able to discriminate between the three groups of subjects with an accuracy of 85.6%. However, the post-NST metabolic profile of GP patients could not be completely assimilated to that of HI. Although NST may produce significant changes in the metabolic profile, GP patients maintained a distinctive fingerprint compared to HI.

Identification of biomarkers could help in assessing periodontal health status and monitoring treatment outcomes. Therefore, the aim of this cross-sectional study was to identify potential innovative salivary biomarkers for the diagnosis of periodontitis using an untargeted proteomic approach. Forty-five healthy non-smoker participants diagnosed as having periodontally healthy conditions (H), severe periodontitis (P), and healthy but reduced periodontium after active periodontal treatment (T) were consecutively enrolled (15 per each group) in the study. A higher number of spots were identified in the proteome of unstimulated whole saliva collected from H and T subjects compared with P group, mainly within the range of 8–40 kDa. Protein spots of interest were analysed by MALDI-TOF-MS, allowing the identification of cystatin SN (CST1) isoform, as confirmed by Western blot. CST1 was markedly expressed in the H group, while it was absent in most P samples (p < 0.001). Interestingly, a distinct CST1 expression was observed in saliva from T patients. CST1 was negatively correlated with the percentage of pathological sites (p < 0.001) and was effective in discriminating active periodontitis from healthy periodontal status (whether H or T). Therefore, salivary CST1 may be a promising non-invasive biomarker for periodontal disease diagnosis and monitoring.