Periodontitis is a destructive disease of the tooth-surrounding tissues. Infection is the etiological cause of the disease, but its extent and severity depend on the immune–inflammatory response of the host. Immune cells use reactive oxygen species to suppress infections, and there is homeostasis between oxidative and antioxidant mechanisms during periodontal health. During periodontitis, however, increased oxidative stress triggers tissue damage, either directly by activating apoptosis and DNA damage or indirectly by activating proteolytic cascades. Periodontal treatment aims to maintain an infection and inflammation-free zone and, in some cases, regenerate lost tissues. Although mechanical disruption of the oral biofilm is an indispensable part of periodontal treatment, adjunctive measures, such as antibiotics or anti-inflammatory medications, are also frequently used, especially in patients with suppressed immune responses. Recent studies have shown that probiotics activate antioxidant mechanisms and can suppress extensive oxidative stress via their ability to activate nuclear factor erythroid 2-related factor 2 (Nrf2). The aim of this narrative review is to describe the essential role of Nrf2 in the maintenance of periodontal health and to propose possible mechanisms to restore the impaired Nrf2 response in periodontitis, with the aid of probiotic and postbiotics.

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

Objective: To monitor salivary B‐cell activating factor (BAFF), tumor necrosis factor‐like weak inducer of apoptosis (TWEAK), and soluble (s)CD163 levels and arginase activity in periodontitis patients following nonsurgical periodontal treatment.Background: BAFF, TWEAK, and sCD163 and arginase are associated with activities of B cells and macrophages, which are important regulators of periodontal immune‐inflammatory response and healing following treatment. Increased salivary BAFF and sCD163 levels and arginase activity in periodontitis have been demonstrated, but their changes following treatment have not been evaluated before.Materials and Methods: Forty‐four Stage III/IV periodontitis patients and 35 periodontally healthy controls were included in the study. Full‐mouth periodontal measurements were recorded and unstimulated saliva was obtained from all participants at baseline. Sample collection and measurements were repeated in periodontitis patients at 2, 6, 12, and 24 weeks following full‐mouth scaling and root debridement, whereas controls were only seen at baseline. BAFF, TWEAK, and sCD163 levels were analyzed with bead‐based multiplexed immunoassay. Arginase activity was measured with Chinard's method.Results: BAFF (p < .001) and sCD163 (p = .003) levels and arginase activity (p < .015) were higher in periodontitis patients compared to healthy controls. BAFF levels (p < .001) and arginase activity (p < .001) of periodontitis patients were reduced at 2 weeks posttreatment and continued to decrease up to 6 (p = .038) and 12 weeks (p = .024), respectively. The reduction of sCD163 levels became significant (p = .003) at 24 weeks posttreatment.Conclusions: The decrease in salivary BAFF levels 2 weeks after periodontal treatment indicates a change in cell signaling toward limited B‐cell activation. Decreasing arginase activity similarly reflects a significant reduction in inflammatory response. The reduction in sCD163 levels that are observed at 24 weeks may reflect a longstanding anti‐inflammatory macrophage activation, given their multiple functions in immune response, inflammation, and healing.

This study aimed to compare tissue levels of CD80 (pro-inflammatory macrophage-related surface marker), CD163, and CD206 (anti-inflammatory macrophage-related surface markers), and their ratios in periodontal and peri-implant health and disease. Altogether, 36 tissue samples were obtained from 36 participants with clinically healthy gingiva (n = 10), healthy peri-implant mucosa (n = 8), periodontitis lesions (n = 9), and peri-implantitis lesions (n = 9). CD80, CD163, and CD206 levels were assessed with immunoblotting. CD163 levels were found to be decreased (p = 0.004), and the CD80/CD163 ratio was found to be elevated (p = 0.002) in periodontitis lesions compared to healthy gingiva. Peri-implantitis lesions showed a tendency towards a higher CD80/CD163 ratio than in healthy peri-implant mucosa with a borderline difference (p = 0.054). No statistically significant difference was detected in CD80, CD163, and CD206 levels of periodontitis lesions when compared to peri-implantitis, and in healthy gingiva when compared to healthy peri-implant mucosa. A disruption in CD80/CD163 balance seems to be related to the pathogenesis of periodontitis and peri-implantitis, being less prominent in the latter. The reason behind this phenomenon may be either suppressed CD163 expression or reduced CD163+ anti-inflammatory macrophage abundance.

Aim: To perform a genome‐wide association study (GWAS) for periodontitis in the FinnGen cohort, as genetic factors contribute to periodontitis.Materials and Methods: We included nearly 250,000 Finnish individuals who had visited a dentist in the public healthcare sector for a clinical oral examination. We designed three periodontitis phenotypes based on diagnosis and procedure codes and CPI indexes in national health registers.Results: We identified 11 independent genetic loci associated with periodontitis, among which 6 were common and novel. A locus near the FST gene was associated with two phenotypes, whereas other lead SNPs were located near ARL15, MFHAS1, DEFB130A and APOE. Additionally, all phenotypes in the discovery and replication cohorts were associated with genetic variations in the HLA region. Furthermore, imputed HLA allele frequencies identified independent associations between HLA‐DRB1, HLA‐DPB1 and HLA‐DQA1 and periodontitis. Based on single‐cell RNA sequencing, the expression of genes near our lead SNPs across all three phenotypes was particularly enriched in gingival cell lineages important in the pathogenesis of periodontitis. Phenotypical and genetic correlations revealed associations between periodontitis and bacterial diseases, as well as autoimmune and cardiometabolic phenotypes.Conclusions: Our GWAS suggests that genetic variation contributing to immune dysregulation is involved in the pathogenesis of periodontitis, which has considerable genetic similarity with other complex traits.

Objective: This study aims to reveal the effects of cyanoacrylate application at the recipient bed and the donor site in free gingival graft surgery on graft dimensions, clinical healing parameters and patient-based outcomes. Methods: Free gingival graft operations were conducted on individuals who were randomly assigned to control or test groups. In the test group, the graft was stabilized and the donor site was coated with cyanoacrylate. In the control group, 6/0 polyvinylidene fluoride sutures were used for stabilization, while the donor site was left untreated. Variables including re-epithelization, post-operative complications, pain, bleeding and quality of life at recipient site, and color match, graft dimensions at donor site were assessed for up to 6 months. Results: Twenty-three individuals completed the study. No differences were observed in any variable between groups except horizontal dimension loss of the graft, which was more abundant in the cyanoacrylate group at six months (p>0.05, p