Bacteriophages: the dawn of a new era in periodontal microbiology?

The oral microbiome, populated by a diverse range of species, plays a critical role in the initiation and progression of periodontal disease. The most dominant yet little-discussed players in the microbiome, the bacteriophages, influence the health and disease of the host in various ways. They, not only contribute to periodontal health by preventing the colonization of pathogens and disrupting biofilms but also play a role in periodontal disease by upregulating the virulence of periodontal pathogens through the transfer of antibiotic resistance and virulence factors. Since bacteriophages selectively infect only bacterial cells, they have an enormous scope to be used as a therapeutic strategy; recently, phage therapy has been successfully used to treat antibiotic-resistant systemic infections. Their ability to disrupt biofilms widens the scope against periodontal pathogens and dental plaque biofilms in periodontitis. Future research focussing on the oral phageome and phage therapy's effectiveness and safety could pave way for new avenues in periodontal therapy. This review explores our current understanding of bacteriophages, their interactions in the oral microbiome, and their therapeutic potential in periodontal disease.

Periodontal inflammatory and microbial profiles in healthy young African Americans and Caucasians.

AIM: This study aimed to compare microbial and inflammatory profiles in periodontally/systemically healthy African American (AA) and Caucasian (C) individuals. MATERIALS AND METHODS: Thirty-seven C and 46 AA aged from 5 to 25 years were evaluated regarding periodontal disease, caries, microbial subgingival profile via 16-s sequencing, as well as salivary and gingival crevicular fluid (GCF) inflammatory profile via multiplex assay. RESULTS: Greater probing depth percentage was detected in AA (p = .0075), while a higher percentage of caries index (p = .0069) and decayed, missing, filled teeth (DMFT) index (p = .0089) was observed in C, after adjusting for number of teeth, sex and age. Salivary levels of IL-6, IL-8 and TNFα were higher for C, whereas GCF levels of eotaxin, IL-12p40, IL-12p70, IL-2 and MIP-1α were higher in AA (p < .05). Different microbial profiles were observed between the races (p = .02). AA presented higher abundance of periodontopathogens (such as Tanerella forsythia, Treponema denticola, Filifactor alocis, among others), and C presented more caries-associated bacteria (such as Streptococcus mutans and Prevotella species). Bacillaceae and Lactobacillus species were associated with higher DMFT index, whereas Fusobacterium and Tanerella species with periodontal disease parameters. CONCLUSIONS: A different inflammatory and bacterial profile was observed between healthy AA and C, which may predispose these races to higher susceptibility to specific oral diseases.

Flavonoids effects against bacteria associated to periodontal disease and dental caries: a scoping review.

This scoping review focused on exploring the efficacy of flavonoids against bacteria associated with dental caries and periodontal diseases. Inclusion criteria comprise studies investigating the antibacterial effects of flavonoids against bacteria linked to caries or periodontal diseases, both pure or diluted in vehicle forms. The search, conducted in August 2023, in databases including PubMed/MEDLINE, Scopus, Web of Science, Embase, LILACS, and Gray Literature. Out of the initial 1125 studies, 79 met the inclusion criteria, majority in vitro studies. Prominent flavonoids tested included epigallocatechin-gallate, apigenin, quercetin, and myricetin. Predominant findings consistently pointed to bacteriostatic, bactericidal, and antibiofilm activities. The study primarily investigated bacteria associated with dental caries, followed by periodontopathogens. A higher number of publications presented positive antibacterial results against Streptococcus mutans in comparison to Porphyromonas gingivalis. These encouraging findings underline the potential applicability of commercially available flavonoids in materials or therapies, underscoring the need for further exploration in this field.

hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice.

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer's disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.

Microbiota Transplantation as an Adjunct to Standard Periodontal Treatment in Periodontal Disease: A Systematic Review.

Periodontitis is a disease linked to severe dysbiosis of the subgingival microbiome. The treatment of periodontitis aims to change the dysbiosis environment to a symbiosis environment. We hypothesized that oral microbiota transplantation can lead to a significant improvement in periodontitis. Therefore, the aim of this study was to determine the effectiveness of microbiota transplantation after standard periodontal treatment in periodontitis patients. The search strategy was carried out by using the Boolean term "AND" to combine the keywords, which were "periodontitis AND microbiota transplantation". Due to the limited resources of the study, we included both in vitro and in vivo investigations in this systematic review. The QUIN risk of bias tool was employed to assess the risk of bias in in vitro studies, while SYRCLE's risk of bias assessment was used for in vivo studies. Oral microbiota transplants (OMTs) have shown potential in treating periodontitis. OMTs significantly reduced periodontitis-associated pathogenic microbial species (P. endodontalis, Prevotella intermedia, T. vincentii, Porphyromonas sp.) and increased beneficial bacteria (P. melaninogenica, Fusobacterium nucleatum, P. catoniae, Capnocytophaga ochracea, C. sputigena, C. gingivalis, Haemophilus parainfluenzae, and Neisseria elongata) upon in vitro testing. Furthermore, in the in vivo tests, single adjunctive OMT also had an effect on the oral microbiota composition compared to the full-mouth mechanical and antimicrobial debridement. OMTs may be cheaper and more effective at addressing high-risk individuals. At present, it is not possible to provide OMT clinical advice due to the lack of available information. This treatment needs to be subjected to more safety and efficacy testing before being included human clinical trials.

Association of Entamoeba gingivalis with Periodontal Disease-Systematic Review and Meta-Analysis.

The oral cavity is a habitat to a diverse range of organisms that make up an essential element of the human microbiota. There are up to 1000 species of micro-organisms capable of colonizing the mouth. Thirty percent of them are uncultivable. The genus Entamoeba includes several species, out of which at least seven of them are able to inhabit the human body (Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii, Entamoeba coli, Entamoeba polecki, Entamoeba hartmann, Entamoeba gingivalis). It was shown that only E. gingivalis is able to colonize the oral cavity. The aim of this study was to evaluate the association and prevalence of E. gingivalis in periodontal disease using two electronic database search engines. In order to have a broader view of the subject, a comprehensive manual search was conducted between 15th February 2023 and 1 April 2023 on these content aggregators and the initial search resulted in 277 articles using the keywords "E. gingivalis", "periodontitis", "E. gingivalis", "periodontal disease", "prevalence", and "incidence", in different combinations. The results showed that 755 patients were infected with E. gingivalis out of a total number of 1729 patients diagnosed with periodontal disease, indicating a global prevalence of 43% in the set of patients analyzed. E. gingivalis was prevalent in 58% of the patients that had gingivitis and in 44% of the patients with periodontitis. Prevalence of E. gingivalis based on gender was 43% in female patients and 47% in male patients. The results indicate that the higher incidence of E. gingivalis in people with periodontal disease compared to healthy people is more than just a sign of the disease; it could also be linked to the severity of the condition and the disease propensity to progress.

The role of probiotics for preventing dysbiosis in periodontal disease: a randomized controlled trial.

Background/aim: Scaling and root planing remain inadequate in periodontitis treatment caused by dysbiotic microbial dental plaque. The aim of this clinical trial is to evaluate the effects of probiotics and kefir consumption in initial periodontal therapy (IPT) on oral microbiota composition and treatment outcomes in patients with periodontitis. Materials and methods: The study was carried out in the Gazi University Department of Periodontology, including a sample size of 36 individuals and utilizing a randomized controlled design. Thirty-six patients with periodontitis were randomly allocated to three groups: one receiving probiotic treatment, another receiving kefir, and a third serving as the control group. Obtaining subgingival microbial samples, we recorded plaque, gingival index, bleeding on probing, periodontal pocket depth, and clinical attachment level (periodontal clinical indices) and then performed IPT. For 14 days, patients took either probiotics, kefir, or no supplements. Data for the first and third months were collected using periodontal clinical indices. DNA sequencing was performed to detect Tannerella forsythia, Porphyromonas gingivalis, and Treponema denticola in subgingival plaque samples collected at baseline and three months. Results: Significant differences were observed regarding periodontal clinical indices among groups in the intragroup comparisons. Moreover, levels of Tannerella forsythia were significantly decreased in all groups. Conclusion: Kefir can be administered in addition to IPT, providing results similar to those observed with probiotics.

Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells.

Periodontal disease is driven by dysbiosis in the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete Treponema denticola, is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins. T. denticola dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that T. denticola dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with T. denticola bacteria revealed significant upregulation of genes associated with extracellular matrix organization and degradation including potentially tissue-specific inducible MMPs that may play novel roles in modulating host immune responses that have yet to be characterized within the context of oral disease. The Gram-negative oral commensal, Veillonella parvula, failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of expression of either abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs while a dentilisin-deficient T. denticola mutant had no effect. Finally, T. denticola-mediated activation of TLR2/MyD88 lead to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all T. denticola-dependent MMP expression. Taken together, these data suggest that T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion.

A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC.

Tyrosine phosphatases are often weaponized by bacteria colonizing mucosal barriers to manipulate host cell signal transduction pathways. Porphyromonas gingivalis is a periodontal pathogen and emerging oncopathogen which interferes with gingival epithelial cell proliferation and migration, and induces a partial epithelial mesenchymal transition. P. gingivalis produces two tyrosine phosphatases, and we show here that the low molecular weight tyrosine phosphatase, Ltp1, is secreted within gingival epithelial cells and translocates to the nucleus. An ltp1 mutant of P. gingivalis showed a diminished ability to induce epithelial cell migration and proliferation. Ltp1 was also required for the transcriptional upregulation of Regulator of Growth and Cell Cycle (RGCC), one of the most differentially expressed genes in epithelial cells resulting from P. gingivalis infection. A phosphoarray and siRNA showed that P. gingivalis controlled RGCC expression through Akt, which was activated by phosphorylation on S473. Akt activation is opposed by PTEN, and P. gingivalis decreased the amount of PTEN in epithelial cells. Ectopically expressed Ltp1 bound to PTEN, and reduced phosphorylation of PTEN at Y336 which controls proteasomal degradation. Ltp-1 induced loss of PTEN stability was prevented by chemical inhibition of the proteasome. Knockdown of RGCC suppressed upregulation of Zeb2 and mesenchymal markers by P. gingivalis. RGCC inhibition was also accompanied by a reduction in production of the proinflammatory cytokine IL-6 in response to P. gingivalis. Elevated IL-6 levels can contribute to periodontal destruction, and the ltp1 mutant of P. gingivalis incited less bone loss compared to the parental strain in a murine model of periodontal disease. These results show that P. gingivalis can deliver Ltp1 within gingival epithelial cells, and establish PTEN as the target for Ltp1 phosphatase activity. Disruption of the Akt1/RGCC signaling axis by Ltp1 facilitates P. gingivalis-induced increases in epithelial cell migration, proliferation, EMT and inflammatory cytokine production.

Periodontal disease and its association to endothelial dysfunction and clinical changes in limited systemic sclerosis: A case-control study.

OBJECTIVES: Periodontal disease occurs frequently in patients with limited cutaneous systemic sclerosis (lcSSc) while data about underlying pathways contributing to periodontal changes are scarce. The aim of this study was to evaluate periodontal disease and to investigate its association with endothelial dysfunction and clinical changes in patients with lcSSc. METHODS: In 38 lcSSc patients and 38 controls, periodontal status was evaluated by disease-specific questionnaire, dental examination including bleeding on probing (BOP), pocket depth, and plaque index, and dental panoramic radiograph. Periodontopathogen bacteria were collected subgingivally using paper points and interleukin-1 (IL-1) gene polymorphisms were evaluated using buccal swabs. Endothelial dysfunction was measured by flow-mediated dilatation, pulse-wave velocity and biochemical analysis, including arginine metabolites and endothelial microparticles. Additionally, lcSSc-specific clinical changes and parameters were recorded. RESULTS: Periodontitis was present in 31 patients with lcSSc (81.6%) and in 27 controls (71.1%) (p = .280). LcSSc patients had a lower teeth number (p = .039) and Eikenella corrodens was to a higher degree detectable in patients with lcSSc (p = .041) while the remaining periodontal parameters revealed no differences between both cohorts. Significant correlations between parameters of arterial stiffness, EUSTAR index, number of teeth and BOP were observed (all p < .05). Detection of Prevotella intermedia was associated with selected IL-1 gene polymorphisms (p = .032) and Porphyromonas gingivalis was associated with severe periodontitis (p = .041). CONCLUSION: Periodontal disease may occur frequently in patients with lcSSc and may be associated with arterial stiffness and with SSc activity.

Proteomics, Lipidomics, Metabolomics, and 16S DNA Sequencing of Dental Plaque From Patients With Diabetes and Periodontal Disease.

Oral microbiome influences human health, specifically prediabetes and type 2 diabetes (Pre-DM/DM) and periodontal diseases (PDs), through complex microbial interactions. To explore these relations, we performed 16S rDNA sequencing, metabolomics, lipidomics, and proteomics analyses on supragingival dental plaque collected from individuals with Pre-DM/DM (n = 39), Pre-DM/DM and PD (n = 37), PD alone (n = 11), or neither (n = 10). We identified on average 2790 operational taxonomic units and 2025 microbial and host proteins per sample and quantified 110 metabolites and 415 lipids. Plaque samples from Pre-DM/DM patients contained higher abundance of Fusobacterium and Tannerella than plaques from metabolically healthy patients. Phosphatidylcholines, plasmenyl phosphatidylcholines, ceramides containing non-OH fatty acids, and host proteins related to actin filament rearrangement were elevated in plaques from PD versus non-PD samples. Cross-omic correlation analysis enabled the detection of a strong association between Lautropia and monomethyl phosphatidylethanolamine (PE-NMe), which is striking because synthesis of PE-NMe is uncommon in oral bacteria. Lipidomics analysis of in vitro cultures of Lautropia mirabilis confirmed the synthesis of PE-NMe by the bacteria. This comprehensive analysis revealed a novel microbial metabolic pathway and significant associations of host-derived proteins with PD.

Salivary leukocyte esterase activity by SillHa is a risk indicator of periodontal disease.

BACKGROUND: There is increasing evidence that diagnostic salivary tests measuring inflammatory biomarkers are being developed to assess inflammatory status for early detection, prevention, and progression of periodontal disease. Therefore, the aim of the present study was to investigate and identify the salivary biomarker that can predict the inflammatory status of periodontal disease. METHODS: A total of 36 patients (28 women and 8 men) with an average age of 57 years were investigated. Unstimulated saliva was collected from the recruited subjects and analyzed using SillHa, a saliva-testing device that measures bacteria count, saliva buffer capacity, acidity, leukocyte esterase, protein, and ammonia. Periodontal parameters were then obtained by clinical examination and initial periodontal therapy was performed. Data obtained with SillHa were compared with clinical periodontal parameters at baseline, re-examination (three months from baseline), and final examination (six months from re-examination). RESULTS: Leukocyte esterase activity in saliva measured by SillHa; BOP and PCR measured by clinical examination showed a significant difference between baseline and final examination and between re-examination and final examination. Patients in the lower median group (group 1) had a significant difference in leukocyte esterase activity between baseline and final examination and re-examination and final examination. In addition, patients in Group 1 had significantly lower BOP between baseline and final examination. While patients in the higher median group (group 2) showed a modest decrease in leukocyte esterase activity, which was significant only between baseline and final examination, no significant changes were observed concerning BOP. Furthermore, the associated systemic disease was observed in 30% and 81.2% of group 1 and 2 patients, respectively. CONCLUSION: The results suggest that leukocyte esterase activity in saliva measured by SillHa could serve as a reliable diagnostic marker for monitoring inflammatory status in periodontal disease.

Porphyromonas gingivalis impairs glucose uptake in skeletal muscle associated with altering gut microbiota.

Skeletal muscles have a high metabolic capacity, which play key roles in glucose metabolism. Although periodontal disease increases the risk of metabolic syndrome, the relationship between periodontal bacterial infection and skeletal muscle metabolic dysfunction is unclear. We found that anti-Porphyromonas gingivalis (Pg) antibody titers positively correlated with intramuscular adipose tissue content (IMAC), fasting blood glucose, and HOMA-IR in metabolic syndrome patients. In C57BL/6J mice fed a high-fat diet, recipients of oral Pg (HFPg) had impaired glucose tolerance, insulin resistance, and higher IMAC compared to recipients of saline (HFco). The soleus muscle in HFPg mice exhibited fat infiltration and lower glucose uptake with higher Tnfa expression and lower insulin signaling than in HFco mice. Gene set enrichment analysis showed that TNFα signaling via NFκB gene set was enriched in the soleus muscle of HFPg mice. Moreover, TNF-α also decreased glucose uptake in C2C12 myoblast cells in vitro. Based on 16S rRNA sequencing, Pg administration altered the gut microbiome, particularly by decreasing the abundance of genus Turicibacter. Microbial network of the gut microbiome was dramatically changed by Pg administration. Our findings suggest that infection with Pg is a risk factor for metabolic syndrome and skeletal muscle metabolic dysfunction via gut microbiome alteration.

Oral bacteria, oral health, and adverse pregnancy outcomes.

The link between oral health and adverse pregnancy outcomes has been suggested by numerous epidemiological studies. More recent studies indicate the relationship between severity of periodontal disease and adverse pregnancy outcomes. Two virulence mechanisms are proposed: direct invasion of oral microorganisms or their components into the fetal-placenta unit and inflammatory mediators produced in the oral cavity affecting the fetal-placenta unit. While interventional periodontal therapy still yielded contradictory results, animal studies suggest that maternal supplementation of omega-3 fatty acids protects the fetus by suppressing inflammation as well as bacteria proliferation in the placenta. This article reviews the recent epidemiological, mechanistic, interventional, and therapeutic studies of oral health and adverse pregnancy outcomes.

Oral-gut bacterial profiles discriminate between periodontal health and diseases.

OBJECTIVE: This investigation explored oral-gut microbial signatures with potential to distinguish among periodontal conditions. BACKGROUND DATA: The interplay between the oral and gut microbiomes may be a critical pathway linking periodontal diseases and systemic inflammatory disorders. The mechanisms by which oral microorganisms translocate to the gut and cause microbial dysbiosis, favoring an inflammatory state, are still unknown. As a first approach, characterization of oral-gut microbial profiles associated with periodontal health and diseases can provide insights on such mechanisms of etiology and pathogenesis. METHODS: Fecal and saliva samples from individuals with periodontal health (PH, 8), gingivitis (GG, 17), and periodontitis (PD, 24) were analyzed for their microbial composition by 16S rRNA gene sequencing. Microbial taxa were compared and correlated to periodontal parameters. Multivariate discriminant analysis (MDA) was carried out to identify profiles related to health and disease. RESULTS: Few significant differences in oral-gut taxa were detected among clinical groups, although increase in fecal Fusobacterium nucleatum ss vincentii and salivary Aggregatibacter actinomycetemcomitans, Parvimonas micra, and Fretibacterium sp. HMT358 were strongly correlated with deep pockets and inflammation (p < .01). Over 50% of the fecal microbiota comprised microorganisms shared between oral and gut sites, whereas oral taxa were detected in approximately 9%, particularly enriched in GG fecal samples (p = .04). Trends for lower fecal richness and higher salivary diversity in PD compared to PH were observed. MDA was able to classify correctly 82% of the patients into the clinical groups. Main classifiers of periodontitis were high BMI, older age, and enrichment of oral-fecal Leptotrichia sp. HMT4, Peptostreptococcus stomatis, Dialister invisus, and a novel Lautropia sp. HMTC89-like organism. CONCLUSION: Within the limitations of an exploratory investigation, specific profiles of oral-gut taxa, including known and potential novel organisms, combined with social-demographic features were able to discriminate individuals with periodontal diseases in this study population.

Effect of Twinlight Laser on the Attachment of Human Gingival Fibroblasts to the Root Surface In Vitro.

BACKGROUND This study aimed to compare the effectiveness of subgingival scaling and root planing with the Twinlight laser, Er: YAG laser, and hand instrumentation on the removal of endotoxin and attachment of human gingival fibroblasts (HGFs) to cementum surfaces in vitro. MATERIAL AND METHODS Single-rooted teeth extracted for periodontal disease were collected and divided into 3 groups: group A, root planing with Gracey curet no. 5/6; group B, irradiation with Er: YAG laser; group C, irradiation with Er: YAG laser and Nd: YAG laser. Endotoxins were determined by the limulus amebocyte lysate test. Cell attachment and proliferation of HGFs on root specimens were evaluated by cell counting kit-8 assay. The root surface and cell morphology were observed by scanning electron microscope. RESULTS A flat root surface with scratches was found in group A, Group B had a homogeneous rough morphology without carbonization, and group C had a non-homogeneous rough morphology with ablation. The endotoxin concentration was highest in group A (P<0.05) and lowest in group C (P>0.05). HGFs cultured in group B showed significantly increased adhesion and proliferation compared with groups A and C (P<0.05). HGFs in group B were well attached, covered densely by pseudopodia. HGFs in group A were round with poor extension and short pseudopodia, while the cells in the group C were in narrow, triangular, or polygonal shapes. CONCLUSIONS Twinlight laser-assisted periodontal treatment effectively improved the biocompatibility of root surface and promoted the attachment and proliferation of fibroblasts by removing calculus and reducing the concentration of endotoxins.

Aggregatibacter actinomycetemcomitans: From Basic to Advanced Research.

Aggregatibacter actinomycetemcomitans is a major periodontal pathogen that was identified firstly in actinomycotic lesions and later in advanced forms of periodontal diseases as well as in oral cavity of healthy subjects. The particular pathogenicity of this specie makes it a target for extensive studies both at fundamental and practical scales. The current advances in experimental and clinical research related to this bacterium focus the light on epidemiologic features, virulence, and invasiveness aspects as well as on identification challenges, bacterial susceptibility, and anti-virulence strategies. The present chapter provide to scientists and periodontal researchers a comprehensive overview on the main advances made in this field with a special focus on epidemiologic dissemination, microbial diagnosis, virulence factors and clinical implementations of such progress.

Host mRNA Analysis of Periodontal Disease Patients Positive for Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Tannerella forsythia.

Periodontal disease is a frequent pathology worldwide, with a constantly increasing prevalence. For the optimal management of periodontal disease, there is a need to take advantage of actual technology to understand the bacterial etiology correlated with the pathogenic mechanisms, risk factors and treatment protocols. We analyzed the scientific literature published in the last 5 years regarding the recent applications of mRNA analysis in periodontal disease for the main known bacterial species considered to be the etiological agents: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Tannerella forsythia. We identified new pathogenic mechanisms, therapeutic target genes and possible pathways to prevent periodontal disease. The mRNA analysis, as well as the important technological progress in recent years, supports its implementation in the routine management of periodontal disease patients.

A Narrative Review on Oral and Periodontal Bacteria Microbiota Photobiomodulation, through Visible and Near-Infrared Light: From the Origins to Modern Therapies.

Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL-RANK signaling axis as well as circulating cytokines/leukocytes and carcinogenesis. Due to the nonconclusive data associating periodontitis and cancer reported in the case and cohort studies, we examine clinical trials relevant to the topic and summarize their outcome.