Microbial- and host immune cell-derived extracellular vesicles in the pathogenesis and therapy of periodontitis: A narrative review.

Periodontitis is a chronic inflammatory disease caused by dysbiotic biofilms and destructive host immune responses. Extracellular vesicles (EVs) are circulating nanoparticles released by microbes and host cells involved in cell-to-cell communication, found in body biofluids, such as saliva and gingival crevicular fluid (GCF). EVs are mainly involved in cell-to-cell communication, and may hold promise for diagnostic and therapeutic purposes. Periodontal research has examined the potential involvement of bacterial- and host-cell-derived EVs in disease pathogenesis, diagnosis, and therapy, but data remains scarce on immune cell- or microbial-derived EVs. In this narrative review, we first provide an overview of the role of microbial and host-derived EVs on disease pathogenesis. Recent studies reveal that Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans-derived outer membrane vesicles (OMVs) can activate inflammatory cytokine release in host cells, while M1 macrophage EVs may contribute to bone loss. Additionally, we summarised current in vitro and pre-clinical research on the utilisation of immune cell and microbial-derived EVs as potential therapeutic tools in the context of periodontal treatment. Studies indicate that EVs from M2 macrophages and dendritic cells promote bone regeneration in animal models. While bacterial EVs remain underexplored for periodontal therapy, preliminary research suggests that P. gingivalis OMVs hold promise as vaccine candidates. Finally, we acknowledge the current limitations present in the field of translating immune cell derived EVs and microbial derived EVs in periodontology. It is concluded that microbial and host immune cell-derived EVs have a role in periodontitis pathogenesis and hence may be useful for studying disease pathophysiology, and as diagnostic and treatment monitoring biomarkers.

An in vitro dynamic bioreactor model for evaluating antimicrobial effectiveness on periodontal polymicrobial biofilms: a proof-of-concept study.

BACKGROUND: The aim of this study was to investigate an in vitro dynamic bioreactor model by evaluating the antimicrobial effect of clinically relevant amoxicillin doses on polymicrobial microcosm biofilms derived from subgingival plaque. METHODS: Biofilms from pooled subgingival plaque were grown for 108  hours in control and experimental dynamic biofilm reactors. Amoxicillin was subsequently infused into the experimental reactor to simulate the pharmacokinetic profile of a standard 500 mg thrice-daily dosing regimen over 5 days and biofilms were assessed by live/dead staining, scanning electron microscopy, and quantitative polymerase chain reaction. RESULTS: Following establishment of the oral microcosm biofilms, confocal imaging analysis showed a significant increase in dead bacteria at 8 hours (p = 0.0095), 48 hours (p = 0.0070), 96 hours (p = 0.0140), and 120 hours (p < 0.0001) in the amoxicillin-treated biofilms compared to the control biofilms. Nevertheless, viable bacteria remained in the center of the biofilm at all timepoints. Significant reductions/elimination in Campylobacter rectus, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Peptostreptococcus anaerobius was observed among the amoxicillin-treated biofilms at the 96 and 120 hour timepoints. CONCLUSION: A novel in vitro dynamic model of oral microcosm biofilms was effective in modeling the antimicrobial effect of a pharmacokinetically simulated clinically relevant dose of amoxicillin.

Epigenetic changes caused by diabetes and their potential role in the development of periodontitis.

AIMS/INTRODUCTION: Periodontal disease, a chronic inflammation induced by bacteria, is closely linked with diabetes mellitus. Many complications associated with diabetes are related to epigenetic changes. However, the exact epigenetic changes whereby diabetes affects periodontal disease remain largely unknown. Thus, we sought to investigate the role of diabetes-dependent epigenetic changes of gingival tissue in the susceptibility to periodontal disease. MATERIALS AND METHODS: We studied the effect of streptozotocin-induced diabetes in minipigs on gingival morphological and epigenetic tissue changes. Accordingly, we randomly divided six minipigs into two groups: streptozotocin-induced diabetes group, n = 3; and non-diabetes healthy control group, n = 3. After 85 days, all animals were killed, and gingival tissue was collected for histology, deoxyribonucleic acid methylation analysis and immunohistochemistry. RESULTS: A diabetes mellitus model was successfully created, as evidenced by significantly increased blood glucose levels, reduction of pancreatic insulin-producing ß-cells and histopathological changes in the kidneys. The gingival tissues in the diabetes group presented acanthosis of both gingival squamous epithelium and sulcular/junctional epithelium, and a significant reduction in the number and length of rete pegs. Deoxyribonucleic acid methylation analysis showed a total of 1,163 affected genes, of which 599 and 564 were significantly hypermethylated and hypomethylated, respectively. Immunohistochemistry staining showed that the hypomethylated genes - tumor necrosis factor-α and interleukin-6 - were positively expressed under the junctional epithelium area in the diabetes group. CONCLUSIONS: Diabetes mellitus induces morphological and epigenetic changes in periodontal tissue, which might contribute to the increased susceptibility of periodontal diseases in patients with diabetes.