Periodontitis is a widespread disease, associated with challenges both in its diagnosis and in selecting from various therapeutic approaches, which do not always yield the expected success. This literature review was conducted to explore diverse therapeutic approaches, especially those focused on nanotechnologies, and their potential contribution to the successful modulation of the host’s response. The effects of the existing microbial diversity and the imbalance of key microbial species in contributing to the progression and worsening of the host’s response in periodontitis are well known. It is essential to understand the role of a well-structured treatment plan for periodontitis, providing opportunities for new research and innovative treatment strategies aimed at reducing the impact of periodontitis on oral and overall systemic health. This will be beneficial for dental professionals, enabling them to effectively prevent and treat periodontitis, ultimately improving the overall health and well-being of patients.

Background: Psychological stress is increasingly recognized as a potential modifier of periodontal disease through both behavioral and biological mechanisms. Cortisol, a key stress hormone, exerts complex immunomodulatory effects and may influence periodontal inflammation and tissue breakdown. This study aimed to compare salivary levels of cortisol, interleukin-1β, and interleukin-6 in patients with varying periodontitis severity and examine their associations with clinical periodontal parameters. Methods: A total of 67 patients diagnosed with periodontitis were classified according to the 2017 World Workshop Classification into Stage I/II vs. Stage III/IV and Grade B vs. Grade C. Unstimulated saliva samples were collected and analyzed for cortisol using electrochemiluminescence immunoassay, and for IL-1β and IL-6 using ELISA. Statistical analyses included Mann-Whitney U test, Spearman’s correlations, and multivariate regression. Results: Median salivary cortisol levels were significantly higher in Stage III/IV (11.90 nmol/L) than in Stage I/II (7.64 nmol/L; p = 0.014) and in Grade C (10.60 nmol/L) vs. Grade B (7.70 nmol/L; p = 0.019). In multivariate analysis, cortisol independently predicted both Stage III/IV (OR = 1.23, p = 0.007) and Grade C (OR = 1.24, p = 0.026) periodontitis. ROC analysis showed that salivary cortisol had moderate diagnostic performance for Stage III/IV periodontitis (AUC = 0.68, cut-off 11.57 nmol/L) and Grade C (AUC = 0.67, cut-off 9.76 nmol/L). Cortisol showed significant positive correlations with clinical markers of disease severity and with IL-1β (r = 0.399, p = 0.001) and IL-6 (r = 0.424, p < 0.001). Conclusions: Salivary cortisol is a promising non-invasive biomarker reflecting both stress-related physiological burden and clinical severity in periodontitis. Cortisol measurement may represent a valuable addition to multifactorial assessments and risk stratification in periodontitis, pending further validation in longitudinal studies.

Background: Periodontitis is a complex disease, and bacterial factors play a crucial role in its initiation. The contributions of genetic and epigenetic factors to the pathogenesis of periodontal disease are increasingly recognized. Single-nucleotide polymorphisms (SNPs) in various molecules, including cytokines, are of particular interest due to their established involvement in numerous diseases. This study investigates the influence of SNPs in the IL-10 gene at positions −592 (rs1800872) C>A and −1082 (rs1800896) T>C (also referred to as 1082A>G) on the severity of periodontitis in a cohort of Bulgarian patients. Methods: In the recent study, both clinical and paraclinical methodologies were employed to comprehensively assess the periodontal status of the participants. The genotypic characterization of IL-10 polymorphisms was performed by PCR RFLP analysis. Statistical analyses, including principal component analysis (PCA), were executed utilizing IBM SPSS Statistics Version 21. Results: We have established a statistically significant association between the presence of at least one A-allele in the patients’ genotype and the incidence of severe periodontitis (p = 0.047). Conclusions: IL-10 single-nucleotide polymorphisms (SNPs) could be effectively considered as biomarkers for the severity of periodontitis.

Salivary cortisol is widely used to investigate stress–periodontitis interactions, but its measurement is affected by methodological limitations. Cortisone, the predominant salivary glucocorticoid, may offer analytical advantages, yet its role in periodontitis remains unexplored. This study evaluated salivary cortisone in relation to periodontal disease severity and compared its performance with cortisol. Sixty-seven periodontitis patients were classified as Stage I/II (n = 32) or Stage III/IV (n = 35). A comprehensive periodontal examination was performed, including FMPS, FMBS, PPD, CAL, BoP, and the BL/Age ratio. Unstimulated morning saliva samples were analyzed for cortisone and cortisol using liquid chromatography–tandem mass spectrometry, and for IL-1β and IL-6 using ELISA. Both cortisone and cortisol levels were significantly higher in Stage III/IV periodontitis (p = 0.014). Cortisone correlated strongly with cortisol (ρ = 0.523, p < 0.001) and was positively associated with IL-6 (ρ = 0.322, p = 0.008) and multiple clinical indicators of periodontal disease severity. ROC analysis showed comparable discriminatory performance for cortisone and cortisol (AUC = 0.675), with cortisone demonstrating higher specificity (94%) for Stage III/IV periodontitis. Our findings suggest that salivary cortisone performs similarly to cortisol and warrants further investigation as an alternative salivary glucocorticoid marker in periodontal research.

The sympathetic nervous system (SNS) is crucial for stress response regulation and immune modulation. Prolonged SNS activation, often induced by stress exposure, disrupts immune homeostasis and intensifies inflammatory processes, contributing to periodontal disease progression. This study investigates the relationship between SNS activity and periodontitis severity, utilizing salivary biomarkers chromogranin A (CgA) and alpha-amylase (sAA) alongside pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6). Saliva samples from 67 patients, categorized by periodontitis severity (Stages I/II and III/IV), were analyzed using enzyme-linked immunosorbent assay (ELISA). The results revealed significantly higher median levels of CgA (9.45 vs. 3.93 pmol/mL) and IL-1β (257.81 vs. 220.11 pg/mL) in patients with Stage III/IV periodontitis compared with those with Stage I/II, indicating heightened SNS activity and inflammatory response. Correlations between these biomarkers and clinical periodontal parameters, such as probing depth and clinical attachment loss, further support these findings. Despite elevated sAA levels in severe cases, statistical significance was not achieved. IL-6 levels also showed no significant variation across disease stages, although trends aligned with increased severity. This study highlights the interplay between SNA activation and periodontal inflammation, as evidenced by elevated salivary levels of CgA and IL-1β in patients with advanced periodontitis. By integrating neuroendocrine and inflammatory biomarkers into the diagnostic process, clinicians may be able to better identify patients at increased risk for periodontal breakdown and to consider adjunctive interventions such as stress management, thereby supporting more personalized approaches to periodontitis treatment.