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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 Alzheimers 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.

Purpose: To investigate the microbiological outcomes obtained with either subgingival debridement (SD) in conjunction with a gel containing sodium hypochlorite and amino acids followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with SD alone. Materials and Methods: Forty-eight patients diagnosed with stages II-III (grades A/B) generalised periodontitis were randomly treated with either SD (control) or SD plus adjunctive sodium hypochlorite/amino acids and xHyA gel (test). Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 3 and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction (PCR)-based method for the identification of detection frequencies and changes in numbers of the following bacteria: Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Tannerella forsythia (T.f), Treponema denticola (T.d), and Prevotella intermedia (P.i). Results: In terms of detection frequency, in the test group, statistically significant reductions were found for P.g, T.f, T.d and P.i (p < 0.05) after 6 months. In the control group, the detection frequencies of all investigated bacterial species at 6 months were comparable to the baseline values (p > 0.05). The comparison of the test and control groups revealed statistically significant differences in detection frequency for P.g (p = 0.034), T.d (p < 0.01) and P.i (p = 0.02) after 6 months, favouring the test group. Regarding reduction in detection frequency scores, at 6 months, statistically significant differences in favour of the test group were observed for all investigated bacterial species: A.a (p = 0.028), P.g (p = 0.028), T.f (p = 0.004), T.d (p <0.001), and P.i (p = 0.003). Conclusions: The present microbiological results, which are related to short-term outcomes up to 6 months post-treatment, support the adjunctive subgingival application of sodium hypochlorite/amino acids and xHyA to subgingival debridement in the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

Frankincense is produced by Boswellia trees, which can be found throughout the Middle East and parts of Africa and Asia. Boswellia serrata extract has been shown to have anti-cancer, anti-inflammatory, and antimicrobial effects. Periodontitis is an oral chronic inflammatory disease that affects nearly half of the US population. We investigated the antimicrobial effects of B. serrata extract on two oral pathogens associated with periodontitis. Using the minimum inhibitory concentration and crystal violet staining methods, we demonstrated that Porphyromonas gingivalis growth and biofilm formation were impaired by treatment with B. serrata extracts. However, the effects on Fusobacterium nucleatum growth and biofilm formation were not significant. Using quantification of colony-forming units and microscopy techniques, we also showed that concentrations of B. serrata that were not toxic for host cells decreased intracellular P. gingivalis infection in human gingival epithelial cells. Our results show antimicrobial activity of a natural product extracted from Boswellia trees (B. serrata) against periodontopathogens. Thus, B. serrata has the potential for preventing and/or treating periodontal diseases. Future studies will identify the molecular components of B. serrata extracts responsible for the beneficial effects.

Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.

Cognitive impairment (CI) is a common complication of the non-motor symptoms in Parkinson's disease (PD), including PD with mild cognitive impairment (PD-MCI) and PD dementia. Recent studies reported the oral dysbiosis in PD and CI, respectively. Porphyromonas gingivalis (P. gingivalis), a pathogen of oral dysbiosis, plays an important role in PD, whose lysine-gingipain (Kgp) could lead to AD-type pathologies. No previous study investigated the composition of oral microbiota and role of P. gingivalis in PD-MCI. This study aimed to investigate the differences of oral microbiota composition, P. gingivalis copy number, and Kgp genotypes among PD-MCI, PD with normal cognition (PD-NC) and periodontal status-matched control (PC) groups. The oral bacteria composition, the copy number of P. gingivalis, and the Kgp genotypes in gingival crevicular fluid from PD-MCI, PD-NC, and PC were analyzed using 16S ribosomal RNA sequencing, quantitative real-time PCR, and MseI restriction. We found that the structures of oral microbiota in PD-MCI group were significantly different compared to that in PD-NC and PC group. The relative abundances of Prevotella, Lactobacillus, Megasphaera, Atopobium, and Howardella were negatively correlated with cognitive score. Moreover, there was a significant difference of Kgp genotypes among the three groups. The predominant Kgp genotypes of P. gingivalis in the PD-MCI group were primarily Kgp II, whereas in the PD-NC group, it was mainly Kgp I. The Kgp II correlated with lower MMSE and MoCA scores, which suggested that Kgp genotypes II is related to cognitive impairment in PD. [ABSTRACT FROM AUTHOR]

Oral bacteria naturally secrete extracellular vesicles (EVs), which have attracted attention for their promising biomedical applications including cancer therapeutics. However, our understanding of EV impact on tumor progression is hampered by limited in vivo models. In this study, we propose a facile in vivo platform for assessing the effect of EVs isolated from different bacterial strains on oral cancer growth and dissemination using the larval zebrafish model. EVs were isolated from: wild-type Aggregatibacter actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; and wild-type Porphyromonas gingivalis. Cancer cells pretreated with EVs were xenotransplanted into zebrafish larvae, wherein tumor growth and metastasis were screened. We further assessed the preferential sites for the metastatic foci development. Interestingly, EVs from the CDT-lacking A. actinomycetemcomitans resulted in an increased tumor growth, whereas EVs lacking the lipopolysaccharide O-antigen reduced the metastasis rate. P. gingivalis-derived EVs showed no significant effects. Cancer cells pretreated with EVs from the mutant A. actinomycetemcomitans strains tended to metastasize less often to the head and tail compared to the controls. In sum, the proposed approach provided cost- and labor-effective yet efficient model for studying bacterial EVs in oral carcinogenesis, which can be easily extended for other cancer types. Furthermore, our results support the notion that these nanosized particles may represent promising targets in cancer therapeutics. [ABSTRACT FROM AUTHOR]

This article discusses a study on the salivary microbiome in patients with periodontitis. The study found that patients with periodontitis had a higher abundance of certain bacteria in their saliva compared to the control group. Specifically, the study identified Fretibacterium species as a potential biomarker for periodontitis screening. However, further research is needed to fully understand the diagnostic and therapeutic implications of these findings. [Extracted from the article]

Infection is a known cause of abdominal aortic aneurysm (AAA), and matrix metalloproteases‐2 (MMP‐2) secreted by vascular smooth muscle cells (SMCs) plays a key role in the structural disruption of the middle layer of the arteries during AAA progression. The periodontal pathogen Porphyromonas gingivalis is highly associated with the progression of periodontitis. GroEL protein of periodontal pathogens is an important virulence factor that can invade the body through either the bloodstream or digestive tract and is associated with numerous systemic diseases. Although P. gingivalis aggravates AAA by increasing the expression of MMP‐2 in animal studies, the molecular mechanism through which P. gingivalis regulates the expression of MMP‐2 is still unknown and requires further investigation.In this study, we first confirmed through animal experiments that P. gingivalis GroEL promotes MMP‐2 secretion from vascular SMCs, thereby aggravating Ang II‐induced aortic remodeling and AAA formation. In addition, rat vascular SMCs and A7r5 cells were used to investigate the underlying mechanisms in vitro. The results demonstrated that GroEL can promote the interaction between the K639 site of MMP‐2 and SUMO‐1, leading to MMP‐2 SUMOylation, which inhibits the reoccurrence of non–K639‐mediated monoubiquitylation. Hence, the monoubiquitylation‐mediated lysosomal degradation of MMP‐2 is inhibited, consequently promoting MMP‐2 stability and production. SUMOylation may facilitate intra‐endoplasmic reticulum (ER) and Golgi trafficking of MMP‐2, thereby enhancing its transport capacity. In conclusion, this is the first report demonstrating the presence of a novel posttranslational modification, SUMOylation, in the MMP family, suggesting that P. gingivalis GroEL may exacerbate AAA formation by increasing MMP‐2 production through SUMOylation in vascular SMCs. This study also provides a novel perspective on the role of SUMOylation in MMP‐2–induced systemic diseases. [ABSTRACT FROM AUTHOR]

Periodontitis and infections with periodontal bacteria have been highlighted as risk factors for dementia. In recent years, attention has been drawn to the role of microglia cells in neurodegenerative diseases. However, there is limited knowledge of the influence of periodontal bacteria on microglia cells. The aim of the present study was to investigate the interactions between the periodontal bacteria Porphyromonas gingivalis and microglia cells and to unravel whether these interactions could contribute to the pathology of Alzheimer's disease. We found, through microarray analysis, that stimulation of microglia cells with P. gingivalis resulted in the upregulation of several Alzheimer's disease-associated genes, including NOX4. We also showed that P. gingivalis lipopolysaccharides (LPS) mediated reactive oxygen species (ROS) production and interleukin 6 (IL-6) and interleukin 8 (IL-8) induction via NOX4 in microglia. The viability of neurons was shown to be reduced by conditioned media from microglia cells stimulated with P. gingivalis LPS and the reduction was NOX4 dependent. The levels of total and phosphorylated tau in neurons were increased by conditioned media from microglia cells stimulated with P. gingivalis or LPS. This increase was NOX4- dependent. In summary, our findings provide us with a potential mechanistic explanation of how the periodontal pathogen P. gingivalis could trigger or exacerbate AD pathogenesis. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a keystone pathogen for periodontal disease. The bacteria are black-pigmented and require heme for growth. P. gingivalis exhibit resistance to many antimicrobial peptides, which contributes to their success in the oral cavity. P. gingivalis W50 was resistant to the antimicrobial peptide LGL13K but susceptible to the all-D-amino acid stereoisomer, DGL13K. Upon prolonged exposure to DGL13K, a novel non-pigmented mutant was isolated. Exposure to the L-isomer, LGL13K, did not produce a non-pigmented mutant. The goal of this study was to characterize the genomic and cellular changes that led to the non-pigmented phenotype upon treatment with DGL13K. The non-pigmented mutant showed a low minimum inhibitory concentration and two-fold extended minimum duration for killing by DGL13K, consistent with tolerance to this peptide. The DGL13K-tolerant bacteria exhibited synonymous mutations in the hagA gene. The mutations did not prevent mRNA expression but were predicted to alter mRNA structure. The non-pigmented bacteria were deficient in hemagglutination and hemoglobin binding, suggesting that the HagA protein was not expressed. This was supported by whole cell enzyme-linked immunosorbent assay and gingipain activity assays, which suggested the absence of HagA but not of two closely related gingipains. In vivo virulence was similar for wild type and non-pigmented bacteria in the Galleria mellonella model. The results suggest that, unlike LGL13K, DGL13K can defeat multiple bacterial resistance mechanisms but bacteria can gain tolerance to DGL13K through mutations in the hagA gene. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Materials and Methods Results Conclusion Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various gastro‐intestinal tract cancers. However, whether P. gingivalis can promote oral squamous cell carcinoma (OSCC) and the underlying mechanism associated with such promotion remain unclear.In this study, OSCC xenograft models were used to evaluate the effects of P. gingivalis on tumor progression. The functional studies were done on several OSCC cell lines in vitro. P. gingivalis‐specific 16S rRNA fluorescent in situ hybridization (FISH) was used to test its prevalence in clinical samples.We found that P. gingivalis increased tumor volume and tumor growth in OSCC nude models. Functional studies demonstrated that P. gingivalis inhibited the apoptosis of OSCC cells by promoting cellular autophagy. P. gingivalis was more prevalent in FISH samples from patients with OSCC than from patients with leukoplakia or healthy subjects (70% vs. 47.2% vs. 33.3%, p = 0.045 and p < 0.001, respectively).These data suggest that P. gingivalis plays an accelerating role in OSCC progression and contributes to OSCC by enhancing the autophagy pathway to reduce carcinoma apoptosis. [ABSTRACT FROM AUTHOR]

Dental infections, such as apical Periodontitis, periodontitis, and peri-implantitis (PI), are closely associated with specific bacterial species, including Streptococcus mutans (S. mutans), Porphyromonas gingivalis (P. gingivalis), and Fusobacterium nucleatum (F. nucleatum), among others. Antibiotics are extensively utilized for prophylactic and therapeutic purposes in the treatment of dental infections and other dental-related issues. Unfortunately, the rapid emergence of antimicrobial resistance has accompanied the increased use of antibiotics in recent years. Specific bacterial pathogens have reached a critical stage of antibiotic resistance, characterized by the proliferation of pan-resistant strains and the scarcity of viable therapeutic alternatives. Therapeutic use of particular bacteriophage (phage) particles that target bacterial pathogens is one potential alternative to antibiotics that are now being seriously considered for treating bacterial illnesses. A kind of virus known as a phage is capable of infecting and eliminating bacteria. Because they can't infect cells in plants and animals, phages might be a harmless substitute for antibiotics. To control oral disorders including periodontitis and dental caries, several research have been conducted in this area to study and identify phages from human saliva and dental plaque. The capacity of these agents to disturb biofilms expands their effectiveness against dental plaque biofilms and oral pathogens in cases of periodontitis, PI, and apical periodontitis. This review summarizes the current antibacterial properties of phages used to treat a variety of dental infections, such as periodontitis, peri-implantitis, infected dentin, and apical periodontitis. [ABSTRACT FROM AUTHOR]

Background: Porphyromonase gingivalis (P. gingivalis) is a type of bacteria that causes periodontitis, which is strongly correlated with systemic diseases such as diabetes. However, the effect of hyperglycemia on periodontitis are unclear. The present study examined the effects of high glucose levels on the response to P. gingivalis infection. Results: The expression of P. gingivalis-induced interleukin-1β (IL-1β) and inflammasomes increased as the glucose concentration increased. High glucose conditions suppressed P. gingivalis–induced autophagy in human acute monocytic leukemia cell line (THP-1) macrophages. Zingerone increased autophagy and alleviated P. gingivalis-induced inflammatory response in THP-1 macrophages under high glucose conditions. In addition, P. gingivalis- induced inflammation in bone marrow-derived macrophages of diabetic mice was higher than in wild-type mice, but a zingerone treatment decreased the levels. Alveolar bone loss due to a P. gingivalis infection was significantly higher in diabetic mice than in wild-type mice. Conclusions: High-glucose conditions aggravated the inflammatory response to P. gingivalis infection by suppressing of autophagy, suggesting that autophagy induction could potentially to treat periodontitis in diabetes. Zingerone has potential use as a treatment for periodontal inflammation induced by P. gingivalis in diabetes patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Materials and Methods Results Conclusion This study aimed to assess the effect of an oscillating chitosan brush (OCB) compared with an ultrasonic device with PEEK tip (US‐PEEK) for mechanical implant surface decontamination using an in vitro model combining 3D models and a validated dynamic multispecies biofilm.A multispecies biofilm using six bacterial strains (Streptococcus oralis, Veillonella parvula, Actinomyces naeslundii, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans) was seeded on dental implants with machined and sandblasted, large‐grit and acid‐etched (SLA) surfaces. These were installed in 3D models depicting peri‐implant defect. Mechanical decontamination was performed for 120 s using either an OCB or a US‐PEEK. A negative control group received no treatment. Scanning electron microscopy (SEM) was used to evaluate the bacterial composition and quantitative PCR (qPCR) analyzed the number of each bacterial species [colony‐forming units per milliliter (CFU/mL)].Well‐structured biofilms with a dense microbial distribution were observed on the negative control implants after 72 h. qPCR following mechanical decontamination showed a scarce bacterial reduction in the OCB group. The US‐PEEK group exhibited a significant decrease in bacterial species compared to both OCB and control groups (p < 0.05). A biofilm removal effect was also observed in the OCB group for the machined implant surfaces.In vitro assessment using an anatomical 3D model showed that mechanical decontamination effectively reduced biofilm. The US‐PEEK group demonstrated biofilm reduction on the SLA surface, while the OCB group showed a reduction on the machined implant surface. Additionally, the US‐PEEK group demonstrated greater efficacy in reducing bacterial numbers. [ABSTRACT FROM AUTHOR]

Superhydrophobic antimicrobial photodynamic therapy (SH‐aPDT) is advantageous wherein airborne singlet oxygen (1O2) is delivered from a device tip to kill a biofilm with no photosensitizer exposure and no bacterial selectivity (Gram + or Gram −). For effective treatment of periodontitis, the frequency of treatment as well as the optical light fluence required is not known. Thus, we sought to determine whether single or repeated SH‐aPDT treatments would work best in vivo using two fluence values: 60 and 125 J/cm2. We assessed the efficacy of three protocols: single treatment; interval treatments (days 0, 2, and 7); and consecutive treatments (days 0, 1, and 2). After 30 days of evaluation, we found that, SH‐aPDT in 3 consecutive treatments significantly decreased Porphyromonas gingivalis levels compared to single and interval SH‐aPDT treatments, as well as SRP‐chlorhexidine (CHX) controls (p < 0.05). Notably, clinical parameters also improved (p < 0.05), and histological and stereometric analyses revealed that consecutive SH‐aPDT treatments were the most effective for promoting healing and reducing inflammation. Our study shows what works best for SH‐aPDT, while also demonstrating SH‐aPDT advantages to treatment of periodontitis including no bacterial selectivity (Gram + or Gram −) and preventing the development of bacterial resistance. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a major pathogenic oral bacterium that is responsible for periodontal disease. It is linked to chronic periodontitis, gingivitis and aggressive periodontitis. P. gingivalis exerts its pathogenic effects through mechanisms such as immune evasion and tissue destruction, primarily by secreting various factors, including cysteine proteases such as gingipain K (Kgp), gingipain R (RgpA and RgpB) and PrtH (UniProtKB ID P46071). Virulence proteins comprise multiple domains, including the pro‐peptide region, catalytic domain, K domain, R domain and DUF2436 domain. While there is a growing database of knowledge on virulence proteins and domains, there was no prior evidence or information regarding the structure and biological function of the well conserved DUF2436 domain. In this study, the DUF2436 domain of PrtH from P. gingivalis (PgDUF2436) was determined at 2.21 Å resolution, revealing a noncanonical β‐jelly‐roll sandwich topology with two antiparallel β‐sheets and one short α‐helix. Although the structure of PgDUF2436 was determined by the molecular‐replacement method using an AlphaFold model structure as a template, there were significant differences in the positions of β1 between the AlphaFold model and the experimentally determined PgDUF2436 structure. The Basic Local Alignment Search Tool sequence‐similarity search program showed no sequentially similar proteins in the Protein Data Bank. However, DaliLite search results using structure‐based alignment revealed that the PgDUF2436 structure has structural similarity Z‐scores of 5.9–5.4 with the C‐terminal domain of AlgF, the D4 domain of cytolysin, IglE and the extracellular domain structure of PepT2. This study has elucidated the structure of the DUF2436 domain for the first time and a comparative analysis with similar structures has been performed. [ABSTRACT FROM AUTHOR]

The oral cavity harbors a diverse and dynamic bacterial biofilm community which is pivotal to oral health maintenance and, if turning dysbiotic, can contribute to various diseases. Glycans as unsurpassed carriers of biological information are participating in underlying processes that shape oral health and disease. Bacterial glycoinfrastructure—encompassing compounds as diverse as glycoproteins, lipopolysaccharides (LPSs), cell wall glycopolymers, and exopolysaccharides—is well known to influence bacterial fitness, with direct effects on bacterial physiology, immunogenicity, lifestyle, and interaction and colonization capabilities. Thus, understanding oral bacterias' glycoinfrastructure and encoded glycolanguage is key to elucidating their pathogenicity mechanisms and developing targeted strategies for therapeutic intervention. Driven by their known immunological role, most research in oral glycobiology has been directed onto LPSs, whereas, recently, glycoproteins have been gaining increased interest. This review draws a multifaceted picture of the glycolanguage, with a focus on glycoproteins, manifested in prominent oral bacteria, such as streptococci, Porphyromonas gingivalis, Tannerella forsythia, and Fusobacterium nucleatum. We first define the characteristics of the different glycoconjugate classes and then summarize the current status of knowledge of the structural diversity of glycoconjugates produced by oral bacteria, describe governing biosynthetic pathways, and list biological roles of these energetically costly compounds. Additionally, we highlight emerging research on the unraveling impact of oral glycoinfrastructure on dental caries, periodontitis, and systemic conditions. By integrating current knowledge and identifying knowledge gaps, this review underscores the importance of studying the glycolanguage oral bacteria speak to advance our understanding of oral microbiology and develop novel antimicrobials. [ABSTRACT FROM AUTHOR]

Introduction: The worldwide prevalence of periodontitis is considerably high, and its pathogenic mechanisms must be investigated and understood in order to improve clinical treatment outcomes and reduce the disease prevalence and burden. The exacerbation of the host immune system induced by oral microbial dysbiosis and the subsequent tissue destruction are the hallmarks of the periodontitis. However, the oral bacteria involved in periodontitis are not fully understood. We used the Oxford Nanopore Technologies (ONT) sequencing system to analyze metagenomic information in subgingival dental plaque from periodontitis and non‐periodontitis patients. The number of Lactobacillus zeae (L. zeae) in the periodontitis patients was 17.55‐fold higher than in the non‐periodontitis patients, suggesting that L. zeae is a novel periodontitis‐associated pathogen. Although several Lactobacillus species are used in vivo as probiotics to treat periodontitis and compete with Porphyromonas gingivalis (P. gingivalis), the roles of L. zeae in periodontitis progression, and the relationship between L. zeae and P. gingivalis needs to be investigated. Methods: Both L. zeae and P. gingivalis were inoculated in the ligature‐implant site of periodontitis mice. We collected mouse gingival crevicular fluid to analyze inflammatory cytokine secretion using a multiplex assay. Intact or sliced mouse maxilla tissue was used for micro‐computed tomography analysis or hematoxylin and eosin staining, immunohistochemistry, and tartrate‐resistant acid phosphatase staining to evaluate alveolar bone loss, neutrophil infiltration, and osteoclast activation, respectively. Results: We observed that L. zeae competed with P. gingivalis, and it increased inflammatory cytokine secretion at the ligature‐implant site. Similar to P. gingivalis, L. zeae promoted ligature‐induced neutrophile infiltration, osteoclast activation, and alveolar bone loss. Discussion: We, therefore, concluded that L. zeae accelerated the progression of periodontitis in the ligature‐induced periodontitis mouse model. [ABSTRACT FROM AUTHOR]

Periodontitis is a common oral bacterial infection characterized by inflammatory responses. Its high prevalence lowers the quality of life for individuals and increases the global economic and disease burden. As microorganisms in dental plaque are responsible for this oral disease, antibacterial drug treatments are effective strategies for preventing and treating periodontitis. In this study, we investigated the inhibitory effect of nicotinamide (NAM), a vitamin B3 derivative, on the growth and virulence of Porphyromonas gingivalis, a key member of the red complex. Our findings revealed that NAM inhibited bacterial growth and gingipain activities, which played a dominant role in protein hydrolysis and heme acquisition. NAM decreased hemagglutination and hemolysis abilities and changed hemin and hemoglobin binding capacities, controlling bacterial infection through a starvation strategy by blocking access to growth‐essential nutrients from the outside and reducing bacterial virulence. Several experiments in an animal model showed the effectiveness of NAM in preventing alveolar bone loss and reducing inflammatory cell infiltration, shedding light on its potential therapeutic applicability. [ABSTRACT FROM AUTHOR]

Background: Malondialdehyde–acetaldehyde (MAA) adducts lead to generation of anti‐MAA autoantibodies and have been independently identified in inflamed periodontal and rheumatoid arthritis (RA) tissues. This study evaluates serum samples from RA cases and osteoarthritis (OA) controls to quantify associations between periodontal clinical measures, alveolar bone loss (ABL), and anti‐Porphyromonas gingivalis, anti‐Prevotella intermedia, and anti‐Fusobacterium nucleatum antibody concentrations with anti‐MAA antibody concentrations. Methods: Participants (n = 284 RA cases, n = 330 OA controls) underwent periodontal clinical assessments and ABL measurements. Serum immunoglobulin (Ig) A, IgG, and IgM anti‐MAA and serum IgG antibacterial antibody concentrations were quantified by enzyme‐linked immunosorbent assay (ELISA). Analyses utilized simple linear regression and multivariable adjusted models. Results: No significant associations of periodontal clinical measures with serum anti‐MAA were found. Moderate (p = 0.038 and p = 0.036, respectively) and high ABL (p = 0.012 and p = 0.014, respectively) in RA cases (but not in OA) were positively associated with IgG and IgM anti‐MAA. Anti‐P. gingivalis and anti‐P. intermedia antibody concentrations were positively associated with IgA (p = 0.001 for both), IgG (p = 0.007 and p = 0.034, respectively), and IgM anti‐MAA antibody concentrations (p < 0.001 and p = 0.020, respectively), while anti‐F. nucleatum was positively associated with IgG anti‐MAA (p = 0.042), findings that were similar across groups. Conclusions: A positive association was demonstrated between ABL and serum IgG and IgM anti‐MAA antibody concentrations that was unique to RA and not observed in OA. Serum anti‐P. gingivalis, anti‐P. intermedia, and anti‐F. nucleatum antibody concentrations displayed significant associations with anti‐MAA antibody in both groups. These findings suggest MAA may play a role in the interrelationship between the periodontium and RA. [ABSTRACT FROM AUTHOR]

The periodontal disease pathobiont Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) may exert a range of detrimental effects on periodontal diseases in general and, more specifically, with the initiation and progression of Localized Stage III Grade C periodontitis (molar–incisor pattern). In this review of the biogeography of this pathobiont, the full range of geographical scales for A. actinomycetemcomitans, from global origins and transmission to local geographical regions, to more locally exposed probands and families, to the individual host, down to the oral cavity, and finally, to spatial interactions with other commensals and pathobionts within the plaque biofilms at the micron/nanoscale, are reviewed. Using the newest technologies in genetics, imaging, in vitro cultures, and other research disciplines, investigators may be able to gain new insights to the role of this pathobiont in the unique initial destructive patterns of Localized Stage III Grade C periodontitis. These findings may incorporate the unique features of the microbiome that are influenced by variations in the geographic environment within the entire mouth. Additional insights into the geographic distribution of molar–incisor periodontal breakdown for Localized Stage III Grade C periodontitis may derive from the spatial interactions between A. actinomycetemcomitans and other pathobionts such as Porphyromonas gingivalis, Filifactor aclocis, and commensals such as Streptococcus gordonii. In addition, while the association of A. actinomycetemcomitans in systemic diseases is limited at the present time, future studies into possible periodontal disease–systemic disease links may also find A. actinomycetemcomitans and its geographical interactions with other microbiome members to provide important clues as to implications of pathobiological communications. [ABSTRACT FROM AUTHOR]

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Chronic periodontitis and its keystone pathogen, Porphyromonas gingivalis, have increasingly been linked with Alzheimer's disease (AD). However, P.gingivalis-lipopolysaccharide (LPS) mediated release of neuroinflammatory proteins contributes to AD remains underexplored. In this study, we utilized data-independent acquisition mass spectrometry to characterize P.gingivalis-LPS induced profile of differentially expressed proteins associated with the neuroinflammatory response in human neuroblastoma (SH-SY5Y) and human microglial (HMC3) cells. We reported a set of 124 proteins in SH-SY5Y cells and 96 proteins in HMC3 cells whose levels were significantly upregulated or downregulated by exposure to P. gingivalis-LPS. Our findings demonstrate that P. gingivalis-LPS contributed to the elevated expressions of dementia biomarkers and pro-inflammatory cytokines that include APP, Aβ1–42, Aβ1–40, T-Tau, p-Tau, VEGF, TGF-β, IL-1β, IL-6 and TNF-α through 2 distinct pathways of extracellular sensing by cell surface receptors and intracellular cytosolic receptors. Interestingly, intracellular signaling proteins activated with P. gingivalis-LPS transfection using Lipofectamine™ 2000 had significantly higher fold change protein expression compared to the extracellular signaling with P. gingivalis-LPS treatment. Additionally, we also explored P. gingivalis-LPS mediated activation of caspase-4 dependent non canonical inflammasome pathway in both SH-SY5Y and HMC3 cells. In summary, P. gingivalis-LPS induced neuroinflammatory protein expression in SH-SY5Y and HMC3 cells, provided insights into the specific inflammatory pathways underlying the potential link between P. gingivalis-LPS infection and the pathogenesis of Alzheimer's disease and related dementias. [ABSTRACT FROM AUTHOR]

Secretory leukocyte protease inhibitor (SLPI) functions as a protease inhibitor that modulates excessive proteolysis in the body, exhibits broad-spectrum antimicrobial activity, regulates inflammatory responses, and plays an important role in the innate immunity. The purpose of the study was to artificially synthesize a SLPI, an antimicrobial peptide, and investigate its effect on antimicrobial activity against Porphyromonas gingivalis and interleukin-6 (IL-6) production. SLPI protein with a molecular weight of approximately 13 kDa was artificially synthesized using a cell-free protein synthesis (CFPS) system and investigated by western blotting and enzyme-linked immunosorbent assay (ELISA). Disulfide bond isomerase in the protein synthesis mixture increased the amount of SLPI synthesized. The synthesized SLPI (sSLPI) protein was purified and its antimicrobial activity was investigated based on the growth of Porphyromonas gingivalis and bacterial adhesion to oral epithelial cells. The effect of sSLPI on IL-6 production in human periodontal ligament fibroblasts (HPLFs) was examined by ELISA. Our results showed that sSLPI significantly inhibited the growth of Porphyromonas gingivalis and bacterial adhesion to oral epithelial cells and further inhibited IL-6 production by HPLFs. These results suggested that SLPI artificially synthesized using the CFPS system may play a role in the prevention of periodontal diseases through its antimicrobial and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Materials and Methods Results Conclusion Periodontal disease is driven by oral pathogens, including Porphyromonas gingivalis, and the release of inflammatory cytokines. These cytokines (e.g., TNF) or their receptors (e.g., IL‐1R) are substrates of a disintegrin and metalloproteinases (ADAMs). In this study, we aimed to determine the effects of ADAMs on periodontal disease phenotypes.Western blot and FRET‐based activity measurements of the gingival crevicular fluid (GCF) of patients were compared with those of infected (P. gingivalis) or cytokine‐stimulated oral keratinocytes and primary human neutrophils, respectively. This was accompanied by an analysis of the released extracellular vesicles and MMP9 activity.In the GCF of patients, ADAM8 protein expression and activity were correlated with disease stage, whereas ADAM10 protein expression was inversely correlated with disease stage. Infection and the resulting cytokine release orchestrated the release of soluble ADAM8 by oral keratinocytes and primary neutrophils as soluble ectodomain and on exosomes, respectively. Furthermore, ADAM8 regulated the release of ADAM10 and MMP9.Dysregulation of cell‐associated and extracellular ADAM proteolytic activity may be an essential regulatory element in the progression of periodontal disease driven by ADAM8. The influence of ADAM8 on disease onset and the evaluation of targeting ADAM8 as a potential and novel local treatment option should be addressed in future translational in vivo studies. [ABSTRACT FROM AUTHOR]

Periodontitis (PDS) is a chronic inflammatory disease initiated by a dysbiosis of oral pathogenic bacterial species, such as Porphyromonas gingivalis (Pg). These bacteria can penetrate the bloodstream, releasing various endo and exotoxins that fuel the infection, and stimulate toxic inflammation in different compartments, including the brain. However, the specific mechanisms by which PDS/Pg contribute to brain disorders, such as Alzheimer's disease (AD), remain unclear. This study assessed the effects of Pg's virulence factors - lipopolysaccharide (LPS-Pg) and gingipains (gps) K (Kgp) and Rgp - on SH-SY5Y cells. Our results demonstrated that LPS-Pg activated signaling through the Toll-like receptor (TLR)-2/4 induced a significant downregulation of G protein-coupled receptor kinase 5 (GRK5). Additionally, LPS-Pg stimulation resulted in a robust increase in Tau phosphorylation (pTau) and p53 levels, while causing a marked reduction in Bcl2 and increased cell death compared to unstimulated cells (Ns). LPS-Pg also elevated inducible nitric oxide synthase (iNOS) expression, leading to oxidative damage. In cells overexpressing GRK5 via Adenovirus, LPS-Pg failed to increase iNOS and pTau levels compared to GFP control cells. High GRK5 levels also prevented the nuclear accumulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, the overexpression of a GRK5 mutant form lacking the nuclear localization signal (ΔNLS) nearly abolished LPS-Pg induced p53 and iNOS upregulation. Finally, we tested whether Kgp and Rgp mediated similar effects and our data showed that both gps caused a marked downregulation of GRK5 leading to increased p53 and pTau levels. In conclusion, this study provides further insight into the toxic effects elicited by Pg in cells and suggests that preventing GRK5 deficiency may be a valid strategy to mitigate Pg-induced toxic effects (i.e. cell death, oxidative damage, and Tau hyperphosphorylation) in SH-SY5Y cells, which are typical molecular hallmarks of neurodegenerative disorders. • Periodontitis represents a causal risk factor for multiple systemic diseases, including neurodegenerative disorders. • Lipopolysaccharide and gingipains from Porphyromonas gingivalis elicited toxic effects in human SH-SY5Y neuroblastoma cells. • Preventing GRK5 downregulation is a potential strategy to abolish Pg-dependent harmful effects induced in human SH-SY5Y neuroblastoma cells. [ABSTRACT FROM AUTHOR]

Periodontitis is a chronic inflammatory disease driven by dysbiosis in subgingival microbial communities leading to increased abundance of a limited number of pathobionts, including Porphyromonas gingivalis and Treponema denticola. Oral health, particularly periodontitis, is a modifiable risk factor for Alzheimer disease (AD) pathogenesis, with components of both these bacteria identified in postmortem brains of persons with AD. Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers. P. gingivalis displays synergistic virulence with T. denticola during periodontitis. The aim of the current study was to determine the ability of P. gingivalis and T. denticola , grown in physiologically relevant conditions, individually and in combination, to induce AD-like pathology following chronic oral inoculation of female mice over 12 weeks. P. gingivalis alone significantly increased all 7 brain pathologies examined: neuronal damage, activation of astrocytes and microglia, expression of inflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 and production of amyloid-β plaques and hyperphosphorylated tau, in the hippocampus, cortex and midbrain, compared to control mice. T. denticola alone significantly increased neuronal damage, activation of astrocytes and microglia, and expression of IL-1β, in the hippocampus, cortex and midbrain, compared to control mice. Coinoculation of P. gingivalis with T. denticola significantly increased activation of astrocytes and microglia in the hippocampus, cortex and midbrain, and increased production of hyperphosphorylated tau and IL-1β in the hippocampus only. The host brain response elicited by oral coinoculation was less than that elicited by each bacterium, suggesting coinoculation was less pathogenic. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria are closely associated with the occurrence, development and metastasis of oral squamous cell carcinoma (OSCC). Antibacterial therapy has been considered an enhancement strategy to suppress bacteria-associated tumors and promote anti-tumor immune responses. Herein, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for the in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis (Pg), one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, composed of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820, was prepared using a simple dissolve-dry-swell solvent exchange method. Upon 808 nm laser irradiation, PNIPAM/DL@TIR exerted photothermal effects to ablate Pg-colonized OSCC and generate dual tumor and bacterial antigens. Owing to its large number of catechol groups, PNIPAM/DL@TIR efficiently captured these antigens to form an in situ antigen repository, thereby eliciting robust and durable antitumor immune responses. Proteomic analysis revealed that the captured antigens comprised both tumor neoantigens and bacterial antigens. The catechol groups endowed PNIPAM/DL@TIR with antioxidant activity, which was also conducive to stimulating antitumor immunity. Altogether, this study develops an injectable adhesive hydrogel and provides a combination strategy for treating bacteria-associated OSCC. In this study, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis , one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, which consists of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820 exhibited outstanding photothermal performance. Owing to the presence of catechol groups, PNIPAM/DL@TIR has good bioadhesive properties and can capture protein antigens to form in situ antigen repository, thus initiating robust and long-term antitumor immune responses. In addition, PNIPAM/DL@TIR exhibited strong antioxidant activity that is favorable for promoting antitumor immunity. In the mouse model of OSCC with bacterial infection, PNIPAM/DL@TIR not only ablated the primary tumors upon NIR laser irradiation, but also induced tumor and bacterial vaccination in situ to suppress distant tumors and lung metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Our previous research showed that Porphyromonas gingivalis (P. gingivalis) infection can activate the inflammatory signaling pathway and promotes the malignancy development of esophageal squamous cell carcinoma (ESCC). However, the prognostic significance of inflammatory response-related genes (IRRGs) in P. gingivalis -infected ESCC requires further elucidation. Hence, our study constructed a prognostic signature based on P. gingivalis and IRRGs to forecast the survival of patients with ESCC, which may provide insight into new treatment options for ESCC patients. Methods: Differentially expressed genes (DEGs) were identified in P.gingivalis -infected and P.gingivalis -uninfected ESCC cell by RNA sequencing. A risk model was constructed and validated using the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database by using univariate Cox regression analysis, LASSO, and the multivariate Cox regression analysis. Kaplan-Meier analysis was carried out to compare the overall survival (OS) between high-risk and low-risk groups. Single-sample gene set enrichment analysis was used to analyze the immune cell infiltration. The Genomics of Drug Sensitivity in Cancer database was used to predict drug sensitivity. Results: There were 365 DEGs between the P.gingivalis -infected and P.gingivalis -uninfected groups. Four genes including DKK1, ESRRB, EREG, and RELN were identified to construct the prognostic risk model (P =.012, C-index = 0.73). In both the training and validation sets, patients had a considerably shorter OS in the high-risk group than those in the low-risk group (P <.05). A nomogram was established using the risk score, gender, and N stage which could effectively forecast the prognosis of patients (P =.016, C-index = 0.66). The high-risk group displayed lower immune infiltrating cells, such as activated dendritic cells, type 2 T helper cells, and neutrophils (P <.05). A total of 41 drugs, including dactinomycin, luminespib, and sepantronium bromide, had a significant difference in IC50 between the 2 subgroups. Conclusion: We demonstrated the potential of a novel signature constructed from 4 P. gingivalis -related IRRGs for prognostic prediction in ESCC patients. [ABSTRACT FROM AUTHOR]

Objective: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs). Design: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related β-galactosidase (SA-β-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry. Results: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-β-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05). Conclusions: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Oral dysbiosis, characterized by an imbalance in the composition of the oral microbiota, has been linked to the initiation and progression of cancer. Dysbiosis induces and exacerbates chronic inflammation that promotes cell proliferation, apoptosis and tumor signaling pathways. In addition, it drives to the indirect metabolism of several substances, including sulfides, nitrosamines, and toxins, which interfere with tumor progression. It also regulates the host immune response, promoting tumor cell survival by interfering with natural killer (NK) cell function. Finally, it influences systemic inflammation and immune dysfunction, contributing to the pathogenesis of various systemic conditions. Furthermore, specific oral bacteria such as Enterococcus faecalis, Fusobacterium nucleatum, and Porphyromonas gingivalis have been related to the progression of oral cancer. These bacteria modulate cellular signaling pathways, immune responses and epithelial-mesenchymal transition in oral cancer cells. Moreover, oral squamous cell carcinoma (OSCC), the most common oral cancer, is influenced by dysbiosis through multiple mechanisms, that include the production of toxins, hormonal imbalance, immune tolerance, and chronic inflammation. Fusobacterium nucleatum, Porphyromonas gingivalis, and Prevotella intermedia have been strongly associated with the development of the OSCC. Understanding the complex interaction between oral dysbiosis and cancer provides insights into potential therapeutic targets and preventive strategies for oral cancer and related diseases. [ABSTRACT FROM AUTHOR]

Beta-thalassemia major is a severe hereditary anemia that necessitates regular blood transfusions, leading to iron overload. This condition also affects various biological markers, including ferritin and vitamin D levels, and can influence immune responses and oral health. The Aim of Study To examine the relationship between salivary Porphyromonas gingivalis IgA and IgG levels with the concentrations of ferritin and vitamin D in adolescent affected by Beta-Thalassemia Major. A case-control study was conducted from November 2023 to June 2024, involving 45 beta-thalassemia major adolescents and 45 healthy controls. All subjects were within ages ranged between 12-17 years. Saliva sample was collected and analyzed for estimation of salivary anti-Porphyromonas gingivalis IgA and IgG by using ELISA and blood collected and analyzed to measures s.ferritin and s.vitamin D by Cobas E411 system. The study group exhibited significantly lower mean salivary anti-Porphyromonas gingivalis IgA and IgG levels (40.59± 16.71 pg/ml), (15.23±3.21 pg/ml) compared to the control group (93.06± 55.25pg/ml), (18.92±3.32 pg/ml) (p=0.000) respectively. Serum ferritin (4158.37±542.64 ng/ml vs. 25.11±10.93 ng/ml), and vitamin D levels (9.83±4.69 ng/ml vs. 16.40±12.93 ng/ml) showed significant differences (p<0.05) between study and control groups. Beta-thalassemia major significantly impacts salivary and serum biochemical markers, highlighting the importance of regular monitoring and potential targeted therapies to manage iron overload and associated complications. The reduced immune response against Porphyromonas gingivalis in these patients suggests a need for enhanced oral health care and possibly prophylactic measures. [ABSTRACT FROM AUTHOR]

Background: Immune cells from rheumatoid arthritis (RA) patients display a reduced in vitro response to Porphyromonas gingivalis (P. gingivalis), which may have functional immune consequences. The aim of this study was to characterize, by flow cytometry, the frequency/activity of monocytes and naturally occurring myeloid dendritic cells (mDCs) in peripheral blood samples from patients with periodontitis and patients with periodontitis and RA. Methods: The relative frequency of monocytes and mDCs in the whole blood, the frequency of these cells producing TNFα or IL-6 and the protein expression levels for each cytokine, before and after stimulation with lipopolysaccharide (LPS) from Escherichia coli plus interferon-γ (IFN-γ), were assessed by flow cytometry, in peripheral blood samples from 10 healthy individuals (HEALTHY), 10 patients with periodontitis (PERIO) and 17 patients with periodontitis and RA (PERIO+RA). Results: The frequency of monocytes and mDCs producing IL-6 or TNF-α and the expression of IL-6 and TNF-α in the PERIO group were generally higher. Within the PERIO+RA group, P. gingivalis and related antibodies were negatively correlated with the monocyte and mDC expression of IL-6. A subgroup of the PERIO+RA patients that displayed statistically significantly lower frequencies of monocytes producing IL-6 after activation presented statistically significantly higher peptidylarginine deiminase (PAD)2/4 activity, anti-arg-gingipain (RgpB) IgG levels, mean probing depth (PD), periodontal inflamed surface area (PISA) and bleeding on probing (BoP). Conclusions: In the patients with PERIO+RA, innate immune cells seemed to produce lower amounts of pro-inflammatory cytokines, which are correlated with worse periodontitis-related clinical and microbiological parameters. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a gram‐negative anaerobic bacterium recognized for its pivotal role in the pathogenesis of periodontal diseases. This review covers an overview of the virulence factors and lifecycle stages of P. gingivalis, with a specific focus on attachment and colonization, biofilm formation, growth and multiplication, dormancy survival and dissemination. Additionally, we explore the significance of inter‐bacterial cross‐feeding within biofilms. Furthermore, we discuss potential phytochemical‐based strategies to target P. gingivalis, including the use of curcumin, apigenin, quercetin and resveratrol. Understanding the virulence factors and lifecycle stages of P. gingivalis, along with the promising phytochemical‐based interventions, holds promise for advancing strategies in periodontal disease management and oral health promotion. [ABSTRACT FROM AUTHOR]

This study explores the potential role and mechanism of Ginsenoside Rb3 (Rb3) in modulating osteoclastogenesis induced by human periodontal ligament fibroblasts (hPLFs) within the periodontitis microenvironment. We investigated the anti‐inflammatory effects of Rb3 on hPLFs stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g‐LPS) utilizing quantitative polymerase chain reaction (qPCR) and enzyme‐linked immunosorbent assay techniques. Moreover, the functional role of Rb3 in hPLFs‐induced osteoclast formation was assessed by treating human bone marrow‐derived macrophages (hBMMs) with conditioned medium from hPLFs, followed by analyses through qPCR, western blot analysis, and staining for tartrate‐resistant acid phosphatase (TRAP) and phalloidin. The impact of Rb3 on the activation of the STAT3 signaling pathway was determined via western blot analysis. Results indicated that Rb3 treatment significantly suppressed the upregulation of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6, MCP‐1, and IL‐18) at both gene and protein levels in hPLFs induced by P.g‐LPS. Furthermore, conditioned medium from Rb3 plus P.g‐LPS treated hPLFs notably decreased the number of TRAP‐positive cells, actin ring formations, and the expression of osteoclast marker genes (including CTSK, NFATC1, and ACP5). Rb3 also inhibited the P.g‐LPS‐induced activation of the STAT3 pathway, with the activation of STAT3 partially reversing the effects of Rb3 on inflammation and osteoclast differentiation. Collectively, Rb3 ameliorates inflammation in P.g‐LPS‐stimulated hPLFs and reduces hPLFs‐induced osteoclastogenesis by inhibiting the STAT3 signaling pathway, suggesting its potential as a therapeutic agent for periodontitis. Highlights: Ginsenoside Rb3 reduces inflammation in human periodontal ligament fibroblasts in a periodontitis microenvironment.Ginsenoside Rb3 inhibits the formation of osteoclasts mediated by human periodontal ligament fibroblasts.The effect of Ginsenoside Rb3 on the inflammation of human periodontal ligament fibroblasts and osteoclast formation is related to the inhibition of the STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is characterized by rapid renal decline. Periodontitis, a chronic oral inflammatory disease, is increasingly associated with renal dysfunction. Although periodontitis is recognized as a contributor to kidney damage, the mechanisms linking it to AKI remain unclear. Methods: This study explored the effects of Porphyromonas gingivalis (P. gingivalis) W83‐infected periodontitis on AKI in C57BL/6J mice, using ischemia‐reperfusion injury 55 days post‐infection. Gingipain inhibitors, KYT‐1 and KYT‐36, were applied. Detection of P. gingivalis was performed using quantitative real‐time polymerase chain reaction (qRT‐PCR) and PCR, while transcriptome sequencing, qRT‐PCR, immunohistochemistry, and immunofluorescence staining assessed renal damage. In vitro, HK‐2 cells were exposed to P. gingivalis at a multiplicity of infection of 10 for 48 h, with inhibition by gingipain or oncostatin M (OSM). Disruption of tight junctions (TJs) was quantified using qRT‐PCR, transepithelial electrical resistance, and cell counting kit‐8 assays. Results: Periodontitis worsened AKI, linked to P. gingivalis infection and renal TJ disruption in the kidney. P. gingivalis infection activated OSM expression, which correlated positively with gingipain. Significantly, OSM and gingipain might collaboratively contribute to the damage of renal TJs, with the reduced expression of TJ proteins. Suppressing gingipain activity presented itself as a protective strategy against the destruction of TJs and the attendant worsening of AKI due to periodontitis. Conclusions: Our study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of P. gingivalis in AKI. [ABSTRACT FROM AUTHOR]

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Bone loss is a major burden for society and impacts people's health all over the world. In a changing world looking toward a more conscious use of raw materials, efforts are being made to increasingly consider new promising biomaterials that account for, on one side, the ability to provide specific functional biological activities and, on the other, the feature of being well tolerated. In this regard, the use of phenolic compounds in the field of bone-related bioengineering shows a rising interest in the development of medical solutions aimed at taking advantage of the multiple beneficial properties of these plant molecules. In this work, the anti-bacterial and anti-inflammatory power of a biphasic calcium phosphate synthetic bone filler coated with a mixture of phenolic compounds was investigated by evaluating the minimal inhibitory concentration (MIC) value against Streptococcus mutans and Porphyromonas gingivalis and the expression of genes involved in inflammation and autophagy by real-time reverse transcription polymerase chain reaction (RT-qPCR) on J774a.1 murine macrophage cells. Results show a MIC of 0.8 μg/mL, a neat anti-inflammatory effect, and induction of autophagy key genes compared to a ceramic bone filler. In conclusion, functionalization with a polyphenol-rich extract confers to a ceramic bone filler anti-bacterial and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD), a common neurodegenerative disease, has been linked to periodontitis, especially Porphyromonas gingivalis (P. gingivalis) infection. This review summarizes the potential mechanisms and pathways through which P. gingivalis and its virulence factors are involved in AD pathogenesis, aiming to provide the scientific basis for the development of novel prevention and treatment strategies for AD. P. gingivalis can promote AD by exacerbating neuroinflammation, facilitating amyloid beta and Tau deposition, and disrupting the blood-brain barrier. Gingipains, secreted by P. gingivalis, serve as core effector molecules by increasing the blood-brain barrier permeability. The association between P. gingivalis and its effectors and AD pathology has been validated by metagenomic analysis and sample detection, indicating that P. gingivalis may be an environmental susceptibility factor or modifiable risk factor for AD. However, the precise mechanisms by which P. gingivalis influences AD, and its interactions with other potential AD-related factors, remain unclear. Moreover, further research needs to be conducted on the therapeutic potential of P. gingvalis intervention in improving AD.

A 61-year-old man in Japan with abdominal pain was suspected of having a renal tumor. Despite initial treatment, his condition rapidly deteriorated, leading to death. Postmortem examination revealed a renal abscess and sepsis caused by Porphyromonas gingivalis. This case underscores the need to consider atypical pathogens in renal masses.

Objective To investigate the impact of metabolic labeling on Porphyromonas gingivalis (Pg) and compare the imaging effects of two fluorescent probes. Methods This study was reviewed by the unit Ethics Committee and was approved by the Experimental Animal Welfare Ethics Branch of the Unit Experimental Biomedical Ethics Committee. Pg integrated N-azidoacetylgalactosamine (Ac4GalNAz) via a bioorthogonal reaction and was labeled with Cy5-DBCO or Cy7-DBCO via a click chemistry reaction. The bacteria were divided into Pg group (control, not fluorescently labeled), Cy5-Pg group (tagged by Cy5-DBCO), and Cy7-Pg group (tagged by Cy7-DBCO). A live/dead staining kit was applied to test the viability of Pg, Cy5-Pg, and Cy7-Pg. The mRNA levels of interleukin-6 (IL-6) and IL-8 and cell proliferation were examined in human gingival fibroblasts (HGFs) after the challenge of Cy5-Pg, Cy7-Pg, or Pg. To investigate the stability of metabolic labeling, Cy5-Pg or Cy7-Pg was cocultured with Escherichia coli (E. coli). Cy5-Pg and Cy7-Pg signal intensity with serial dilutions were examined using an in vivo imaging system (IVIS). Finally, C57BL/6J mice were orally administered Cy5-Pg or Cy7-Pg for IVIS detection, and the signal-to-background ratios were calculated. Results Metabolic labeling could be applied to label live Pg in vitro. The optimal labeling concentrations for Cy5 and Cy7 were 20 μmol/L and 30 μmol/L, respectively. The area ratios of live to dead bacteria were approximately 2.0 in the three groups (F = 0.318, P>0.05). After a 6-h challenge with Cy5-Pg, Cy7-Pg, or Pg, the mRNA levels of HGFs increased by 7.86-, 7.46-, and 6.56-fold for IL-6, respectively (F = 40.886, PF = 18.781, PP>0.05). HGFs were further challenged by Cy5-Pg, Cy7-Pg, or Pg at different MOIs, and cell proliferation was significantly inhibited (MOI = 104∶1, F = 153.52, P5∶1, F = 331.21, P6∶1, F = 533.65, PP>0.05). Within 24 h of co-culturing Cy5-Pg or Cy7-Pg with E. coli, minimal E. coli was detected. The intensities of Cy5 and Cy7 remained stable for 3 h. Additionally, the fluorescence signal intensities of Cy5 and Cy7 were linearly correlated with the concentration (R2 = 0.97). After oral gavage of Cy5-Pg or Cy7-Pg in mice for the abdominal region at 1 h and 3 h, the signal-to-background ratios of Cy7-Pg were approximately 4.24-fold (t = 6.893, Pt = 4.407, PPg. For the isolated gastrointestinal tracts at 3 h, the signal-to-background ratio of Cy7-Pg was 5.19-fold higher than that of Cy5-Pg (t = 4.418, P

Background: Porphyromonas gingivalis, highly virulent bacteria, is said to play an important role in the pathogenesis of periodontal disease and rheumatoid arthritis (RA). Chronic periodontitis (CP) is a microbial-induced inflammatory disease leading to tooth loss if undetected and untreated. RA is a systemic inflammatory disease affecting the joints with subsequent morbidity and mortality. These two diseases share a common pathobiology. Although the presence of P. gingivalis has been investigated as a bridging link between these two diseases, its quantification has not been fully elicited. Hence, this case–control study primarily aimed at quantifying P. gingivalis using real-time quantitative polymerase chain reaction (qPCR) and secondarily assess the influence of age and gender on the clinical and biochemical parameters of these two diseases. Materials and Methods: The study population consisted of 51 patients divided into two age groups, i.e., 35–55 and 55–76 years. Twenty-five patients belonged to the test group (RA with CP) and 26 to the control group (CP without RA). Both the groups were analyzed for quantification of P. gingivalis using the qPCR technique along with periodontal and biochemical parameters. The study also analyzed the influence of age and gender on clinical characteristics. Results: P. gingivalis count was exponentially raised in younger females having CP with RA. Age had no effect on clinical variables in CP patients with and without RA. However, gender comparison revealed RA factor and erythrocyte sedimentation rate to be more sensitive for females with significant relationship. Conclusion: P. gingivalis count increased exponentially in CP patients with RA compared to those without RA. Younger females harbored more P. gingivalis.

Abstract Over the last decade, accumulating evidence has suggested that tumor-associated macrophages (TAMs) play a significant role in the tumor development. This commentary wishes to highlight the findings by You, et al. that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma (OSCC) via the IL6/Stat3/THBS1 feedback loop. These unprecedented findings identified M1-like TAMs-regulated processes as potentially tumor-promotion in the context of OSCC immunomicroenvironment.

Background: Periodontal disease is the leading cause of tooth loss, and an association between periodontal disease and non-oral systemic diseases has been shown. Formation of biofilm by periodontal pathogens such as Fusobacterium nucleatum, Porphyromonas gingivalis, and Streptococcus mutans and their resistance to antimicrobial agents are at the root of persistent and chronic bacterial infections. Methods: The bactericidal effect of far-ultraviolet (F-UV) light irradiation at 222 nm on periodontal bacteria was assessed qualitatively and quantitatively. The effect of biofilm disruption by F-UV light on periodontal bacteria was examined by crystal violet staining, and the morphologic changes of the biofilm after F-UV irradiation were explored by confocal laser microscopy and scanning electron microscopy. We developed a thin fiber-type 222 nm F-UV irradiator and studied its safety and effect of reducing bacteria in rodent models. Results: F-UV light at 222 nm had a bactericidal effect on F. nucleatum, P. gingivalis, and S. mutans. Irradiation with F-UV light reduced the biofilm formed by the bacteria and sterilized them from within. Confocal laser microscopy showed a clear reduction in biofilm thickness, and scanning electron microscopy confirmed disintegration of the biofilm architecture. F-UV irradiation was less damaging to DNA and less cytotoxic than deep-ultraviolet light, and it reduced bacterial counts on the tooth surface. Conclusion: F-UV irradiation has the potential to destroy biofilm and act as a bactericide against pathogenic bacteria in the biofilm.

Objective: The objective of this study was to evaluate the antibacterial efficacy of wax apple (Syzygium samarangense) fruit extracts (aqueous and ethanol) against Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. Methodology: The stock solution was prepared for microbial analysis (100 mg/ml). A disc diffusion test to determine the zone of inhibition and the serial broth dilution test to determine the minimum inhibitory concentration were done to assess the antimicrobial activity. Data obtained were appraised observationally and interpreted. Results: When assessed for antibacterial activity of extracts by disc diffusion method, both aqueous and ethanolic extracts did not show a zone of inhibition on P. gingivalis and A. actinomycetemcomitans. However, the aqueous extract showed an inhibition zone of 8 mm at the concentration of 50 and 75 µl/ml against F. nucleatum. Similarly, the ethanolic extract showed an inhibition zone of 8 mm at 50 µl/ml and 9 mm at 75 µl/ml volume against F. nucleatum. When assessed for antibacterial activity of extracts by serial broth dilution method, only P. gingivalis (both aqueous and ethanolic extracts at 50 µg/ml) and F. nucleatum (aqueous extracts at 1. 6 µg/ml and ethanolic extract at 0.4 µg/ml) exhibited antibacterial effect, whereas A. actinomycetemcomitans was completely resistant to both extracts at all the concentrations. Conclusion: In the present in vitro study, S. samarangense (wax apple) showed its antibacterial activity against F. nucleatum only by exhibiting MIC at 1.6 µg/ml for aqueous and 0.4 µg/ml for ethanolic extract, but no antibacterial activity was shown against P. gingivalis and A. actinomycetemcomitans.

Abstract Background Epidemiological studies have demonstrated that periodontitis is an independent risk factor for chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the association between these two diseases remains unclear. The lung microbiota shares similarities with the oral microbiota, and there is growing evidence to suggest that the lung microbiome could play a role in the pathogenesis of COPD. This study aimed to investigate whether periodontal pathogens could contribute to the pathogenesis of COPD in a mouse model. Methods We established mouse models with oral infection by typical periodontal pathogens, porphyromonas gingivalis (Pg group) or fusobacterium nucleatum (Fn group), over a three-month period. Mice that did not receive oral infection were set as the control group (C group). We assessed the level of alveolar bone resorption, lung function, and histological changes in the lungs of the mice. Additionally, we measured the levels of inflammatory factors and tissue damage associated factors in the lung tissues. Results Lung function indices, including airway resistance, peak inspiratory/expiratory flow and expiratory flow-50%, were significantly reduced in the Fn group compared to the C group. Additionally, histological examination revealed an increased number of inflammatory cells and bullae formation in the lung tissue sections of the Fn group. Meanwhile, levels of inflammatory factors such as IL-1β, IL-6, IFN-γ, and TNF-α, as well as tissue damage associated factors like matrix metalloproteinase-8 and neutrophil elastase, were significantly elevated in the lung tissue of the Fn group in comparison to the C group. The Pg group also showed similar but milder lung changes compared to the Fn group. Pg or Fn could be detected in the lungs of both oral infected groups. Conclusion The results indicated that oral periodontal pathogens infection could induce COPD-like lung changes in mice, and they may play a biological role in the association between periodontitis and COPD.

Background/purpose: Periodontitis is associated with various systemic diseases, potentially facilitated by the passage of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs). Several recent studies have suggested a connection between Pg-OMVs and neuroinflammation and neurodegeneration, but the precise causal relationship remains unclear. This study aimed to investigate the mechanisms underlying these associations using in vitro models. Materials and methods: Isolated Pg-OMVs were characterized by morphology, size, and gingipain activity. We exposed SH-SY5Y neuroblastoma cells and BV-2 microglial cells to various concentrations of Pg-OMVs. Cell morphology, a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, an enzyme-linked immunosorbent assay, and Western blot analysis were used to evaluate the cellular mechanism underlying Pg-OMV-induced neurotoxicity in neuronal cells and inflammatory responses in microglial cells. Results: Exposure to Pg-OMVs induced neurotoxicity in SH-SY5Y cells, as evidenced by cellular shrinkage, reduced viability, activation of apoptotic pathways, and diminished neuronal differentiation markers. Gingipain inhibition mitigated these effects, suggesting that gingipain mediates Pg-OMVs-induced neurotoxicity in SH-SY5Y cells. Our research on neuroinflammation suggests that upon endocytosis of Pg-OMVs by BV-2 cells, lipopolysaccharide (LPS) can modulate the production of inducible nitric oxide synthase and tumor necrosis factor-alpha by activating pathways that involve phosphorylated AKT and the phosphorylated JNK pathway. Conclusion: Our study demonstrated that following the endocytosis of Pg-OMVs, gingipain can induce neurotoxicity in SH-SY5Y cells. Furthermore, the Pg-OMVs-associated LPS can trigger neuroinflammation via AKT and JNK signaling pathways in BV-2 cells.

Background: Periodontitis is a multifactorial, polymicrobial oral inflammatory illness brought on by oral pathogens. Porphyromonas gingivalis is a Gram-negative, obligatory anaerobic, black-pigmented coccobacillus and is regarded as a primary etiological factor in the progression of periodontitis. Rapid, highly senstitive and specific detection methods are emerging. The present study aimed to evaluate the loop-mediated isothermal amplification (LAMP) technique for efficiently detecting P. gingivalis from subgingival plaque samples of chronic periodontitis patients. Materials and Methods: This study included 50 subgingival plaque samples from patients suffering from chronic periodontitis. The DNA (Deoxyribonucleic acid) was extracted by the “modified proteinase K” method. A set of six primers, targeting the pepO gene of P. gingivalis, was used for conducting LAMP. The amplification was visualized by naked-eye detection and agarose electrophoresis. Conventional polymerase chain reaction (PCR) and real-time qantitative PCR (qPCR) were carried out by targeting the 16SrRNA (16S ribosomal ribonucleic acid) gene of P. gingivalis. Results: The results showed that LAMP detected P. gingivalis in 40 out of 50 samples (80%). Whereas, qPCR and conventional PCR technique detected P. gingivalis in 38 (76%) and 33 (66%) samples respectively. The sensitivity and specificity of the LAMP method were 94.87% and 90.90%, respectively. With qPCR, the sensitivity and specificity were found to be 92.30% and 81.81%, respectively, whereas, with conventional PCR, it was found to be 76.92% and 72.72%, respectively. Conclusion: LAMP is an efficient technique for quick, accurate, and reliable identification of P. gingivalis from subgingival plaque samples. The technique needs to be validated analytically, and further studies can be conducted by taking saliva and/or gingival crevicular fluid samples from periodontitis patients.

Abstract Periodontitis is a chronic inflammatory disease that affects the periodontal tissues. Although it is associated with various systemic diseases, the impact of periodontitis on kidney transplantation (KT) outcomes, particularly allograft rejection, remains unclear. This study investigated the effect of periodontitis on transplant immunity, specifically examining Porphyromonas gingivalis-derived lipopolysaccharide (LPS-PG). In vitro experiments revealed that LPS-PG increased regulatory T cells (Tregs) in Lewis rat spleen cells. In a mixed lymphocyte reaction assay, concentrations of interferon-γ, indicative of alloreactivity, were lower than in controls when LPS-PG was added to the culture and when LPS-PG-administered Lewis rat spleen cells were used as responders. In a rat KT model, LPS-PG administration to recipients promoted mild tubulitis and low serum creatinine and blood urea nitrogen levels 5 days post-KT compared with PBS-administered controls. Furthermore, LPS-PG-administered recipients had an elevated Treg proportion in their peripheral blood and spleen cells, and increased infiltrating Tregs in kidney allografts, compared with controls. The elevated Treg proportion in peripheral blood and spleen cells had a significant negative correlation with serum creatinine, suggesting elevated Tregs modulated allograft rejection. These findings suggest that periodontitis might modulate alloimmune reactivity through LPS-PG and Tregs, offering insights to refine immunosuppressive strategies for KT recipients.