Periodontal Disease

Abstract: For nearly a century, researchers have associated periodontal disease (PD) with risks of other adverse health outcomes such as cardiovascular disease, diabetes mellitus, and respiratory diseases, as well as adverse pregnancy outcomes. Those findings have led to the hypothesis that PD causes those adverse health outcomes either by increasing systemic inflammation or by the action of periodontopathic bacteria. However, experiments largely failed to support that hypothesis. Instead, the association is casual, not causal, and is due to shared underlying modifiable risk factors, including smoking, diet, obesity, low levels of physical activity, and low vitamin D status. Diabetes mellitus is also considered a risk factor for PD, whereas red and processed meat are the most important dietary risk factors for diabetes. Because PD generally develops before other adverse health outcomes, a diagnosis of PD can alert patients that they could reduce the risk of adverse health outcomes with lifestyle changes. In addition, type 2 diabetes mellitus can often be reversed rapidly by adopting an anti-inflammatory, nonhyperinsulinemic diet that emphasizes healthful, whole plant-based foods. This review describes the evidence that proinflammatory and prohyperinsulinemia diets and low vitamin D status are important risk factors for PD and other adverse health outcomes. We also make recommendations regarding dietary patterns, food groups, and serum 25-hydroxyvitamin D concentrations. Oral health professionals should routinely inform patients with PD that they could reduce their risk of severe PD as well as the risks of many other adverse health outcomes by making appropriate lifestyle changes.

Objectives: Periodontitis and rheumatoid arthritis (RA) are two widespread chronic inflammatory diseases with a previously suggested association. The objective of the current study was to compare the oral microbial composition and host´s inflammatory mediator profile of saliva samples obtained from subjects with periodontitis, with and without RA, as well as to predict biomarkers, of bacterial pathogens and/or inflammatory mediators, for classification of samples associated with periodontitis and RA. Methods: Salivary samples were obtained from 53 patients with periodontitis and RA and 48 non-RA with chronic periodontitis. The microbial composition was identified using 16S rRNA gene sequencing and compared across periodontitis patients with and without RA. Levels of inflammatory mediators were determined using a multiplex bead assay, compared between the groups and correlated to the microbial profile. The achieved data was analysed using PCoA, DESeq2 and two machine learning algorithms, OPLS-DA and sPLS-DA. Results: Differential abundance DESeq2 analyses showed that the four most highly enriched (log2 FC >20) amplicon sequence variants (ASVs) in the non-RA periodontitis group included Alloprevotella sp., Prevotella sp., Haemophilus sp., and Actinomyces sp. whereas Granulicatella sp., Veillonella sp., Megasphaera sp., and Fusobacterium nucleatum were the most highly enriched ASVs (log2 FC >20) in the RA group. OPLS-DA with log2 FC analyses demonstrated that the top ASVs with the highest importance included Vampirovibrio sp. having a positive correlation with non-RA group, and seven ASVs belonging to Sphingomonas insulae, Sphingobium sp., Novosphingobium aromaticivorans, Delftia acidovorans, Aquabacterium spp. and Sphingomonas echinoides with a positive correlation with RA group. Among the detected inflammatory mediators in saliva samples, TWEAK/TNFSF12, IL-35, IFN-α2, pentraxin-3, gp130/sIL6Rb, sIL-6Ra, IL-19 and sTNF-R1 were found to be significantly increased in patients with periodontitis and RA compared to non-RA group with periodontitis. Moreover, correlations between ASVs and inflammatory mediators using sPLS-DA analysis revealed that TWEAK/TNFSF12, pentraxin-3 and IL-19 were positively correlated with the ASVs Sphingobium sp., Acidovorax delafieldii, Novosphingobium sp., and Aquabacterium sp. Conclusion: Our results suggest that the combination of microbes and host inflammatory mediators could be more efficient to be used as a predictable biomarker associated with periodontitis and RA, as compared to microbes and inflammatory mediators alone.

The presence of periodontal diseases (PDs) often strongly correlates with other severe chronic inflammatory conditions, including cardiovascular disease, diabetes, and arthritis. However, the mechanisms through which these diseases interact are unclear. In PD, tissue and bone destruction in the mouth is driven by elevated recruitment of polymorphonuclear neutrophils (PMNs), which are primed and recruited from the circulation to sites of inflammation. We predicted that systemic effects on PMN mobilization or priming could account for the interaction between PD and other inflammatory conditions. We tested this using a mouse model of ligature-induced PD and found elevated PMN counts specifically in bone marrow, supporting a systemic effect of periodontal tissue inflammation on PMN production. In contrast, mice with induced peritonitis had elevated PMN counts in the blood, peritoneum, and colon. These elevated counts were further significantly increased when acute peritonitis was induced after ligature-induced PD in mice, revealing a synergistic effect of multiple inflammatory events on PMN levels. Flow cytometric analysis of CD marker expression revealed enhanced priming of PMNs from mice with both PD and peritonitis compared to mice with peritonitis alone. Thus, systemic factors associated with PD produce hyperinflammatory PMN responses during a secondary infection. To analyze this systemic effect in humans, we induced gingival inflammation in volunteers and also found significantly increased activation of blood PMNs in response to ex vivo stimulation, which reverted to normal following resolution of gingivitis. Together, these results demonstrate that periodontal tissue inflammation has systemic effects that predispose toward an exacerbated innate immune response. This indicates that peripheral PMNs can respond synergistically to simultaneous and remote inflammatory triggers and therefore contribute to the interaction between PD and other inflammatory conditions. This suggests larger implications of PD beyond oral health and reveals potential new approaches for treating systemic inflammatory diseases that interact with PD.

Periodontitis refers to a wide range of the inflammatory conditions of supporting dental structures. For some patients with periodontitis, antibacterial agents are needed as an adjuvant to mechanical debridement treatments and oral hygiene maintenance. However, the widespread use of broad-spectrum antibiotics for the prophylaxis and treatment of periodontal infections results in the emergence of resistant pathogens. Therefore, probiotics have become markedly interesting to researchers as a potentially safe alternative to periodontal treatment and maintenance. Probiotics have been used in medicine for decades and extensively applied to the treatment of inflammatory diseases through the modulation of microbial synergy and other mechanisms. A growing amount of evidence has shown that using Lactobacillus strains for oral cavity maintenance could improve periodontal health. In this study, we reviewed studies showing proof of the inhibitory effects of Lactobacillus species on periodontal inflammation. We also explored the rationale and potential for using Lactobacillus species in the management of periodontitis.

Peri-implantitis has a polymicrobial etiology and is a major cause of dental implant loss. Various clinical protocols for its prevention and treatment have been proposed; however, some cases show a rapid progression with non-resolving clinical symptoms. To clear a means of differentiating between such cases, the implants with peri-implantitis in this study were categorized as the active group and the remission group and that two kinds of samples were obtained from the same subjects (n = 20). The microbiome was analyzed through pyrosequencing of the 16S rRNA gene. From LEfSe results, Porphyomonas, Fusobacterium, Treponema, Tannerella, and other periodontal pathogens were abundant in the active group, while lactic acid bacteria (Lactobacillales and Bifidobacterium) were abundant in the remission group.

Peri-implant diseases are considered to be a chronic destructive inflammatory destruction/damage occurring in soft and hard peri-implant tissues during the patient’s perennial use after implant restoration and have attracted much attention because of their high incidence. Although most studies seem to suggest that the pathogenesis of peri-implant diseases is similar to that of periodontal diseases and that both begin with microbial infection, the specific mechanism of peri-implant diseases remains unclear. As an oral opportunistic pathogen, Fusobacterium nucleatum (F. nucleatum) has been demonstrated to be vital for the occurrence and development of many oral infectious diseases, especially periodontal diseases. More notably, the latest relevant studies suggest that F. nucleatum may contribute to the occurrence and development of peri-implant diseases. Considering the close connection between peri-implant diseases and periodontal diseases, a summary of the role of Fusobacterium nucleatum in periodontal diseases may provide more research directions and ideas for the peri-implantation mechanism. In this review, we summarize the effects of F. nucleatum on periodontal diseases by biofilm formation, host infection, and host response, and then we establish the relationship between periodontal and peri-implant diseases. Based on the above aspects, we discuss the importance and potential value of F. nucleatum in peri-implant diseases.

Objective: To examine the risk of developing benign or malignant colorectal tumors in patients with periodontitis within 15 years using Taiwan’s National Health Insurance Database.

Background: Studies have shown that colorectal carcinoma often develops under inflammatory conditions and changes of microbiota in the gut. Recently, a link between Fusobacterium nucleatum, a periodontal pathogen, and colorectal carcinoma has been proposed. However, whether periodontitis is a risk of developing colorectal tumor remains uncertain.

Methods: In total, 35 124 participants were enrolled from 2000 to 2015 to examine the development risk of benign colorectal tumors, including 11 708 patients with periodontitis who received therapy (group 1), 11 708 patients with periodontitis not receiving periodontal treatment (group 2), and 11 708 non-periodontitis controls after matching for gender, age, and index year. To examine the risk of developing colorectal malignancy, 11 720 participants were assigned to each of the three groups. Cox proportional hazards model and Kaplan-Meier methods were used to compare the risks. Sensitivity analysis was performed, excluding the diagnoses during the first 1 or 5 years.

Results: After the follow-up, 177, 154, and 63 participants in group 1, group 2, and control group had benign colorectal tumors. Patients with periodontitis tended to be associated with a greater rate of having a benign colorectal tumor. The adjusted hazard ratios (aHRs) were 3.77 (95% confidence interval [CI] 2.01-4.82, p < .001) and 2.85 (95% CI 1.62-3.74, p < .001) for groups 1 and 2, respectively. Regarding the risk of malignant colorectal tumor, 20, 18, and 14 participants who developed malignant tumors were included in group 1, group 2, and control group; however, no significant increase in malignancy was observed in periodontitis groups (aHR1.92, 95% CI 0.74-2.36, p = .482; aHR 1.50, 95% CI 0.68-1.97, p = .529, for the two periodontitis groups, respectively).

Conclusions: The results of this study suggest that patients with periodontitis may have an increased risk of developing benign, but not malignant, colorectal tumors.

Gingival and Periodontal diseases represent a major concern both in dentistry and medicine. The majority of the contributing factors and causes in the etiology of these diseases are reduced or treated with ozone in all its application forms (gas, water, oil). The beneficial biological effects of ozone, its anti-microbial activity, oxidation of bio-molecules precursors and microbial toxins implicated in periodontal diseases and its healing and tissue regeneration properties, make the use of ozone well indicated in all stages of gingival and periodontal diseases. The primary objective of this article is to provide a general review about the clinical applications of ozone in periodontics. The secondary objective is to summarize the available in vitro and in vivo studies in Periodontics in which ozone has been used. This objective would be of importance to future researchers in terms of what has been tried and what the potentials are for the clinical application of ozone in Periodontics.

We performed a comprehensive microbiome analysis of root caries lesions using 22 teeth extracted from patients with severe periodontitis. The carious lesions were mechanically collected and cryo-pulverized following tooth extraction. Differences in the microbiome were compared between independent lesions at the supragingival site (SG) and lesions extending beyond the gingival margin (GCB). DNA was extracted and the microbiome was characterized on the basis of the V3-V4 hypervariable region of the 16S rRNA gene using paired-end sequencing on an Illumina MiSeq device. The microbiota in root caries lesions showed compositionally distinct microbiota depending on the location. The most abundant OTUs in the SG group were Streptococcus (26.0%), Actinomyces (10.6%), and Prevotella (7.6%). GCB presented Prevotella (11.1%) as the most abundant genus, followed by Fusobacterium (9.6%) and Actinomyces (8.7%). The SG group showed a lack of uniformity in microbiota compared with the GCB group. The bacterial profiles of GCB varied considerably among patients, including periodontal pathogens such as Porphyromonas, Selenomonas, Filifactor, Peptococcus, and Tannerella. Periodontal pathogens inhabit root caries lesions that extend beyond the gingival margin. This study provides a new perspective for elucidating the microbial etiology of root caries.