Periodontal Pathogens Research Articles

Impact of Aggregatibacter actinomycetemcomitans on epithelial repair

ABSTRACT: Normal wound healing occurs in four overlapping stages - hemostasis, inflammation, proliferation, and remodeling. In the oral cavity, these processes occur in an infectious environment. Among the pathogens found in the oral community, Aggregatibacter actinomycetemcomitans (Aa) constitutes a well-recognized periodontal pathogen responsible for expressing several virulence factors, which activate a host response. Aim: This study investigated whether Aa’s presence can interfere with oral keratinocyte tissue healing in an in vitro wound healing model. Methods: Two groups were defined: Group KO (n=5) and Group KO+Aa (n=5). The Aa (JP2 strains) were cultivated in anaerobiosis, and the total protein extract was obtained. The keratinocytes were cultivated with the medium of standard culture until their confluence. After confluence, plates were allocated to each group. With the pipette’s tip, a “scratch” was made in the middle of each well of the plate, and the cells were cultured at 37°C in a humidified atmosphere with 5% CO2. The cells received the stimulus according to groups, and, at times 0, 5, 10, 24, and 48 hours, the wound areas were visualized and standardly recorded using an inverted microscope. Results: When analyzing the timeframe, differences in wound measurements indicate a faster closure in the control group compared to the KO+Aa group, although not statistically significant. However, upon examining the wound closure measures, it was observed that the Aa protein extract significantly reduced wound closure at 10 and 48 hours (p<0.05), negatively impacting the keratinocyte’s behavior. Conclusion: In summary, it was demonstrated that the pathogen Aa can interfere with the re-epithelization in vitro.

Pattern Recognition Receptors in Periodontal Disease: Molecular Mechanisms, Signaling Pathways, and Therapeutic Implications

Periodontal disease remains a significant global health concern, characterized by complex host–pathogen interactions leading to tissue destruction. This review explored the role of pattern recognition receptors (PRRs) in the pathogenesis of periodontal disease, synthesizing current knowledge on their molecular mechanisms and potential as therapeutic targets. We examined the diverse family of PRRs, focusing on toll-like receptors (TLRs) and NOD-like receptors (NLRs), elucidating their activation by periodontal pathogens and subsequent downstream signaling cascades. This review highlights the intricate interplay between PRR-mediated pathways, including NF-κB and MAPK signaling, and their impact on inflammatory responses and bone metabolism in periodontal tissues. We discussed the emerging concept of PRR crosstalk and its implications for periodontal homeostasis and disease progression. Furthermore, this review addressed the potential of PRR-targeted therapies, exploring both challenges and opportunities in translating molecular insights into clinical applications. By providing an overview of PRRs in periodontal health and disease, this review aims to stimulate future research directions and inform the development of novel diagnostic and therapeutic strategies in periodontology.

Anti-Porphyromonas gingivalis Antibody Levels in Patients With Stroke and Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) and stroke are two highly related conditions, with periodontitis and periodontal pathogens, such as Porphyromonas gingivalis (Pg), appearing to be the most prominent common risk factors. In this study, we evaluated studies assessing Pg infection via serum/plasma anti-Pg antibodies in patients with AF and/or stroke. Online databases (PubMed, Scopus, Embase, and the Web of Science) were screened for studies showing the association between anti-Pg antibodies with stroke and/or AF. Relevant data were extracted, and a subsequent random-effects meta-analysis was performed to calculate the pooled odds ratio (OR) or standardized mean difference (SMD) and 95% confidence intervals (CIs) for Pg seropositivity or anti-Pg antibody levels in stroke patients compared to controls. Sixteen studies were included in the systematic review. Based on the meta-analysis performed, there was no significant difference in Pg IgA and IgG levels between patients with stroke and controls (IgA: SMD 0.11, 95% CI -0.02 to 0.25, p = 0.1; IgG: SMD -0.12, 95% CI -1.24 to 0.99, p = 0.83). Similarly, no difference was observed between these groups in terms of Pg IgA and IgG seropositivity (IgA: OR 1.63, 95% CI 1.06-2.50, p = 0.026; IgG: OR 2.30, 95% CI 1.39-3.78, p < 0.001). Subsequently, we reviewed the results of six articles investigating serum or plasma IgG antibodies against Pg in patients with AF. Our results revealed a strict association between Pg infection and AF, with AF patients exhibiting either higher anti-Pg antibody levels or a higher prevalence of positive serum Pg antibodies. Our study supports the clinical utility of Pg infection assessment in patients with periodontitis and those with AF and solicits more focused studies to corroborate its use in clinical settings to enhance overall outcomes, reduce the risk of complications like stroke, and help fine-tune personalized therapies.

ApoEVs Transfer Mitochondrial Component to Modulate Macrophages in Periodontal Regeneration.

Macrophages are key players in the host immune response to periodontal pathogens and tissue repair. The aim of this study was to explore the potential of apoptotic cell-derived extracellular vesicles (ApoEVs) in modulating the mitochondrial function of macrophages as a mean to enhance periodontal tissue regeneration. ApoEVs were extracted from periodontal ligament stem cells (PDLSCs) and characterized to observe their effects on macrophage function. Invivo experiments, ApoEVs were mixed with hyaluronic acid and injected into the periodontal pockets of rats with periodontitis to observe their impact on periodontal tissue regeneration and the immune microenvironment. Functional assays were conducted to confirm whether ApoEVs contained mitochondrial components and which specific components were transferred to regulate macrophage function. The experimental findings showed that treatment of ApoEVs efficiently restored the homeostasis of macrophage and improved tissue regeneration in a periodontitis rat model. Mechanism investigation demonstrated that the efferocytosis of ApoEVs resulted in the transfer of mitochondrial components from PDLSCs to macrophage. The increased mitochondrial components within macrophages improved mitochondrial function and polarization of macrophages towards the anti-inflammatory M2 phenotype, resulting in the improvement of inflammatory environment in periodontal tissues. ApoEVs can transfer mtDNA to enhance mitochondrial function in macrophages, fostering their transition to an anti-inflammatory phenotype. Ultimately, this process improves the immune microenvironment in periodontitis and promotes periodontal tissue regeneration.

IDENTIFICATION OF PERIODONTAL PATHOGENS IN PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS DEPENDING ON THE SEVERITY OF INFLAMMATION

Introduction. The progression of chronic generalized periodontitis is associated with gram-negative anaerobic bacteria. Microbiological diagnostics of periodontal disease provides an opportunity for selecting the most effective therapeutic approach for both local and systemic conditions in patients. Aim of this study is to conduct a qualitative assessment of the presence of pathogenic microorganisms in the periodontal pockets of patients, based on the severity of inflammation. Materials and methods. The presence of five key pathogenic microorganisms in the periodontal pocket contents of 90 individuals aged 25-60 years (45 with grade I severity and 45 with grade II) was assessed using real-time polymerase chain reaction (PCR). The analysis was conducted with the CFX96™ Real-Time PCR Detection System (BIO-RAD) and the PeriodontScreen Real-TM reagent kit (Sacace Biotechnologies Srl, Italy). Non-parametric correlation statistical analysis was performed to calculate Kendall’s Tau and Gamma coefficients. In 27 patients (60%) with grade I severity, bacteria of a single species were identified. Two types of periodontal pathogens were detected in 13 patients (28.9%), with the most common combination being Tannerella forsythia and Aggregatibacter actinomycetemcomitans, found in 5 patients (11.1%); 5 patients (11.1%) showed the presence of three microbial species: Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis. Among the patients with grade II severity, 8 patients (17.8%) had bacteria of one species, specifically Prevotella intermedia. Two microbial species were identified in 9 patients (20%), while three species were present in 15 patients (33.3%). The most frequent combination included Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans, found in 5 patients (11.1%). Four types of microbes were detected in 13 patients (28.9%), with the predominant combination being Tannerella forsythia, Porphyromonas gingivalis, Treponema denticola, and Aggregatibacter actinomycetemcomitans (17.8%). None of the patients with grade II severity had all five periodontopathogenic agents. The correlation analysis confirmed that chronic periodontitis is strongly associated with the presence of Tannerella forsythia within microbial associations. Conclusions. The spectrum of periodontal pathogens affects the severity of inflammation in the periodontium. In grade II inflammation, associations of periodontal pathogens were detected by 82.2% of cases, while in grade I by in 40%. Tannerella forsythia was detected in 42.2% of patients with grade I inflammation, 15.6% of them as a mono-infection; in patients with grade II inflammation in 71.1%, in associations with Treponema denticola in 48.9%. Determining the spectrum of periodontal pathogens, taking into account their characteristics and associated virulence factors, is necessary for choosing the effective differentiated treatment approach.

Clinical and Microbiological Periodontal Biofilm Evaluation of Patients with Type I Diabetes

Background/Objectives: The purpose of this study was to assess the microbial composition and density of subgingival plaque samples for periodontal pathogens while correlating the values with glycemic control levels via glycated hemoglobin (HbA1c), a type of hemoglobin that has chemically linked glucose, in type I diabetes individuals who will undergo complex oral rehabilitation through orthodontic treatment and implant surgery. Methods: A cohort of 42 adults with type I diabetes were included in this study. The subjects sustained a comprehensive periodontal clinical examination as well as microbiological assessments of their subgingival plaque samples through quantitative real-time PCR. The samples were collected from the two deepest pockets of each subject. Results: The highest number of periodontopathogenic bacteria was observed in the pockets of 5–7 mm. T. forsythia showed the highest prevalence (20.48%), with decreasing numbers as follows: T. denticola (13.31%), P. gingivalis (11.26%), A. actinomycetemcomitans (7%), and P. intermedia (4.9%). T. denticola and T. forsythia were significantly more commonly observed in individuals with elevated HbA1c serum levels. No correlation was observed between P. gingivalis, A. actinomycetemcomitans, P. intermedia presence, and the HbA1c value. Conclusions: Periodontopathogenic agents’ presence in subgingival biofilm samples varied in accordance with the pocket probing depth and metabolic control of the diabetic individuals. In our study, the appearance of these periodontopathogenic agents was linked to lowered metabolic control in patients with type I diabetes mellitus.

Association between serum antibodies to oral microorganisms and nonalcoholic fatty liver disease in adults

BackgroundAlterations in the bacteria, such as the periodontal bacteria, might be considered potential risk factors for nonalcoholic fatty liver disease (NAFLD). Most studies analyzing this association have focused mainly on a specific periodontal bacteria (Porphyromonas gingivalis) and have involved relatively small study populations (tens or hundreds of individuals). To address this gap, a sizable, nationally representative adult population was utilized to investigate the association between the incidence of NAFLD and high serum IgG antibodies for 19 periodontal bacteria.MethodsTo explore this association, data from the Third National Health and Nutrition Examination Survey (NHANES III)—which provides a cross-sectional representation of the noninstitutionalized U.S. population, encompassing 33,994 individuals—were analyzed. Participants aged 40 years and above with data on NAFLD—determined by the gold standard of ultrasound examination (USON)—as well as comprehensive records of serum IgG antibodies against periodontal bacteria, were included, resulting in a final analysis subset of 6,330 individuals.ResultsUsing a cluster analysis based on the Socransky classification scheme for oral microorganisms, antibody titers for the 19 bacteria were grouped into four clusters—Red-Green, Orange-Blue, Yellow-Orange, and Orange-Red. When these clusters, as well as individual antibody relationships with NAFLD, were examined, the adjusted odds ratios (ORs) ranged from 0.958 [95% confidence interval (CI): 0.916, 1.003] to 1.021 [95% CI: 0.987, 1.055]. This indicated that no statistically significant associations were found (P > 0.05), underscoring the absence of a meaningful link.ConclusionsIn summary, it was discovered that there is currently no evidence to correlate serum antibodies to periodontal pathogens with NAFLD in the nationally representative NHANES III.Clinical trial numberNot applicable.

Evaluation of Periodontitis and Fusobacterium nucleatum Among Colorectal Cancer Patients: An Observational Cross-Sectional Study.

Periodontitis has been associated with an increased risk of CRC, as well as a worse prognosis due to increased inflammation mediators and carcinogenic factors. Moreover, direct and indirect virulence factors from periodontal pathogens, such as Fusobacterium nucleatum, could play a pivotal role in malignant transformation and progression. This cross-sectional study aims to evaluate the presence and the stage of periodontitis in a cohort of patients with CRC. The secondary aim is to assess the presence of F. nucleatum and its relationship with patients' general characteristics, concomitant pathologies, tumor characteristics, and drug therapy. Patients affected by CRC underwent dental examination and periodontal charting with the "North Carolina" probe to assess the presence and stage of periodontitis, according to the new classification of periodontal diseases of the World Workshop of the European Federation of Periodontology (EFP) and the American Academy of Periodontology (AAP) 2017. F. nucleatum presence was assessed by a dorsal tongue swab and related to the patient's general characteristics, concomitant pathologies, tumor characteristics, and drug therapy. Periodontal disease was found in 94.3% of I/II CRC stage patients and 100% of III/IV CRC stage patients. Severe periodontitis was found in 76% of the advanced CRC stage and 87.9% of patients with initial CRC, while initial periodontitis was found in 12.1% of initial CRC and 24% of late CRC stages, respectively, without significant differences. F. nucleatum presence showed no correlation between the patient's and tumor's characteristics, comorbidities, and drug assumed. Periodontal disease showed a high prevalence among CRC patients. Moreover, severe periodontitis has a higher prevalence in CRC patients compared to initial periodontitis. F. nucleatum presence was unrelated to CRC stage, site, other comorbidities, and drug therapies. With these data, it is not possible to admit a direct relationship between CRC and periodontal disease, but further case-control studies must be carried out to further prove this aspect. Preventive and operative targeted strategies to maintain a healthy oral status are suggested in CRC patients.

Photodynamic therapy in the treatment of periodontal diseases. Literature review

Periodontal diseases affect about 90% of the adult population, but the treatment regimens for this pathology are different, with varying degrees of effectiveness. One of the causes of inflammatory phenomena is the microbial factor. In some cases, there is a need for antimicrobial prescriptions, which, against the background of growing antibiotic resistance, becomes a problem. This article describes the possibilities of using such a method of influencing periodontal pathogens as photodynamic therapy. The main conclusions of studies on the effectiveness of PDT in inflammatory periodontal diseases are presented.

Periodontal pathogens in the appearance and progression of chronic periodontitis

Periodontal diseases are considered a public health problem due to their high prevalence worldwide, so the authors set out to describe the role of periodontal pathogens in the onset and progression of chronic periodontitis. The documentary analysis method was used and a total of 18 bibliographies were reviewed. Current scientific evidence supports the association between periodontal pathogens and the development of periodontitis, demonstrating that bacteria such as Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola play a crucial role in the pathogenesis of periodontal disease by triggering inflammatory responses and promoting the destruction of tooth-supporting tissues.

Evaluation of A. actinomycetemcomitans and P. gingivalis from the mouth of patients irradiated in the head and neck region: a cross-sectional study.

This study aimed to quantify Aggregatibacter actinomycetemcomitans (A.a) and Porphyromonas gingivalis (P.g) from the mouth of head and neck irradiated and cancer-free patients. Information such as age, presence of tongue coating, salivary flow, and biofilm were collected from head and neck irradiated patients (Group 1) and compared the results with a group of cancer-free individuals (Group 2). The presence of tongue coating was clinically examined. Sialometry was performed through a stimulating technique by chewing paraffin. Microbiological samples were collected from buccal and labial mucosa and tongue dorsum. Subsequently, the samples were processed and analyzed by qPCR to detect the presence and quantify the bacteria. There was a statistical difference in the quantity of bacteria among the 24 individuals in Group 1 (A.a, 2817 ± 8718; P.g, 3145 ± 11297) and 26 individuals in Group 2 (A.a, 133996 ± 398545; P.g, 60 ± 195) regarding tongue coating (Group 1, A.a 2194.6 ± 4641.5; Group 2, A.a 92767.8 ± 333385.7) and salivary volume (Group 1, 0.69mL; Group 2, 3.09mL). The linear regression analysis found that the variable group was the main responsible for the difference in the quantity of periodontal pathogens (p-value < 0.001). There was no statistical difference in the amount of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis between totally edentulous and partially edentulous (with 12 or fewer teeth) patients. Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were present in significant amounts in patients of both groups, with a greater quantity in cancer-free individuals.

Assessment of Oral Bacterial Microflora in Patients with Stable Chronic Obstructive Pulmonary Disorders

Background &amp; Objectives: Chronic obstructive pulmonary disorder is an inflammatory disease characterized by the progressive deterioration of pulmonary function and increasing airway obstruction, includes chronic bronchitis and emphysema. The oral cavity has been considered a potential reservoir for respiratory pathogens. Oral bacteria may play a vital role in the exacerbation of chronic obstructive pulmonary diseases. Hence, we intend to study the bacterial microflora of oral cavity in stable COPD patients. Methods: In this study 20 patients aged between 20 to 60 years diagnosed with stable COPD and 20 normal healthy controls were selected based on the set inclusion and exclusion criteria. A detailed case history, physical examination and investigations and all the subjects were examined for gingival and periodontal status by recording the Oral hygiene which comprises debris index and calculus index and periodontal index and Quantitative oropharyngeal cultures were obtained by oral washing using isotonic saline as the collecting fluid. Results: A significant higher score of OHI(S) and PI was observed in COPD patients. There is a direct correlation between periodontal pathogens with the severity of COPD. Conclusion: The predominant organisms found in the oropharyngeal secretions were porphyromonas gingivalis and haemophilus influenza, in COPD patients.

Porphyromonas gingivalis GroEL accelerates abdominal aortic aneurysm formation by matrix metalloproteinase-2 SUMOylation in vascular smooth muscle cells: A novel finding for the activation of MMP-2.

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.

Formulation and evaluation of herbal gel containing ethanolic extract of Momordica charantia against socransky’s periodontal pathogens of the oral cavity-an in vitro study

Background: Periodontitis is a multifaceted disease initiated by periodontal pathogens which when left untreated results in inflammation of the supporting tissues of the teeth, resorption of alveolar bone, loss of the periodontal ligament attachment, periodontal pocket formation and/or recession of the gingiva. Hence, the current study aimed at evaluating the efficacy of Momordica charantia leaves extract on Socransky’s periodontal pathogens and formulating a herbal gel for subgingival local drug delivery for the potential treatment of moderate periodontitis. Methods: M. charantia leaves were authenticated from a recognized taxonomist. They were coarsely powdered following which an ethanol-based extract preparation was done. The extract obtained was then assessed for minimum inhibitory concentration, minimum bactericidal concentration followed by gel formulation which was then subjected to time kill assay and zone of inhibition on periodontal pathogens, the efficacy of which was comparatively evaluated against 0.12% chlorhexidine (CHX) gluconate. Kruskal-Wallis Test was employed with the statistical significance set at p≤0.05. Results: The concentration of M. charantia ethanolic extract against periodontal pathogens was determined to be 1 gm/100 ml and a statistically significant difference was found in the effectiveness between the gel so formulated and CHX. Conclusion: The antibacterial activity was evident in the ethanolic extract of M. charantia which when used to formulate a herbal gel against anaerobic periodontal pathogens demonstrated efficacy comparable to that of CHX.

Porphyromonas gingivalis Promotes Oral Squamous Cell Carcinoma Progression by Modulating Autophagy.

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 invitro. P. gingivalis-specific 16S rRNA fluorescent insitu 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.

Characterization of thioredoxin-thioredoxin reductase system in Filifactor alocis.

Filifactor alocis is a newly appreciated member of the periodontal community with a strong periodontal disease correlation. Little is known about the survival mechanisms by which F.alocis copes with oxidative stress and establishes the infection within the local inflammatory microenvironment of the periodontal pocket. The aim of this study is to investigate if F.alocis putative peroxiredoxin/AhpC protein FA768 may constitute an alkyl hydroperoxide reductase system utilizing putative thioredoxin reductase protein FA608, and putative thioredoxin/glutaredoxin homolog FA1411/FA455. FA768, FA608, FA1411 and FA455 proteins from F.alocis were expressed and purified from Escherichia coli. Insulin and 5,5-dithio-bis-2-nitrobenzoic acid (DTNB) reduction assays were performed to determine if purified FA1411 and FA455 proteins could be a substrate for FA608. The peroxidase activity of FA768 was examined by measuring its ability to reduce hydrogen peroxide (H2O2) with FA608 and FA1411/FA455 provided as the reducing systems. Further, the hydroperoxide substrate specificity of FA768 was analyzed by monitoring the NADPH oxidation in the presence of different peroxides, including H2O2, cumyl hydroperoxide (CHP), and tert-butyl hydroperoxide (t-BHP). In this study, we have demonstrated the existence of a functioning thioredoxin-dependent alkyl hydroperoxide system in F.alocis. This system is comprised of a thioredoxin reductase (FA608), a thioredoxin/glutaredoxin homolog (FA1411/FA455), and a typical 2-cysteine peroxiredoxin/AhpC (FA768). FA608, together with FA1411/FA455, can function as a thioredoxin reductase system to reduce insulin, DTNB, and FA768. FA455 is a glutaredoxin-like protein with thioredoxin functions in F.alocis. Both the FA768/FA608/FA1411 and FA768/FA608/FA455 reductase systems were NADPH-dependent and exhibited specificity for broad hydroperoxide substrates H2O2, CHP, and t-BHP. This is the first study of a thioredoxin dependent alkyl hydroperoxide system from a periodontal pathogen. This system is proposed to protect F.alocis against oxidative stress due to the likely absence of a catalase or an additional peroxiredoxin homolog.

Correlation between Periodontitis and Onset of Alzheimer's Disease: A Literature Review.

Alzheimer's disease is a slowly progressing neurodegenerative illness and the most common form of dementia. This pathology leads to an increase in cognitive decline and is responsible, in patients, for several difficulties in performing various activities of daily living, such as oral hygiene. Several experimental studies have shown that oral health in patients with Alzheimer's disease worsens in direct proportion to the progression of the disease due to the appearance of gingivitis and periodontitis. This clinical literature review aims to evaluate a possible correlation between periodontal disease and Alzheimer's disease, trying to understand if the periopathogens can contribute to the onset or the progression of Alzheimer's disease (AD). The study was conducted on the database PubMed (MEDLINE) of full-text systematic reviews in English on humans and animals that were published in the last five years, from 2018 to 2023. This returned 50 publications, which, once the eligibility criteria were applied, resulted in the 10 publications examined in this review. The selected articles were organized through the construction of tables, analyzed, and compared through Judith Garrard's Matrix method to arrive at the review results. Infection by periopathogens can increase the risk of developing Alzheimer's disease, but also the onset of the latter can make it more difficult to maintain proper oral hygiene, favoring the onset of periodontal disease: it is possible to affirm the existence of a correlation between periodontitis and AD. It was found that patients exposed to chronic periodontitis have a greater risk of developing a cognitive decline or AD and that oral pathogens can be responsible for neuropathologies and increasing systemic inflammation. Periodontitis and periodontal pathogens represent a real risk factor for the onset or worsening of AD; however, the pathogenetic mechanism is still not completely clear.

Discovery, characterization, and structure of a cofactor-independent histidine racemase from the oral pathogen Fusobacterium nucleatum

Fusobacterium nucleatum is an oral commensal bacterium that can act as an opportunistic pathogen, and is implicated in diseases such as periodontitis, adverse pregnancy outcomes, colorectal cancer, and Alzheimer’s disease. F. nucleatum synthesizes lanthionine for its peptidoglycan, rather than meso-2,6-diaminopimelic acid (DAP) used by most Gram-negative bacteria. Despite lacking the biosynthetic pathway for DAP, the genome of F. nucleatum ATCC 25586 encodes a predicted DAP epimerase. A recent study hypothesized that this enzyme may act as a lanthionine epimerase, but the authors found a very low turnover rate, suggesting that this enzyme likely has another more favored substrate. Here, we characterize this enzyme as a histidine racemase (HisR), and found that catalytic turnover is ∼10,000× faster with L-histidine than with L,L-lanthionine. Kinetic experiments suggest that HisR functions as a cofactor-independent racemase and that turnover is specific for histidine, while crystal structures of catalytic cysteine to serine mutants (C67S or C209S) reveal this enzyme in its substrate-unbound, open conformation. Currently, the only other reported cofactor-independent histidine racemase is CntK from Staphylococcus aureus, which is used in the biosynthesis of staphylopine, a broad-spectrum metallophore that increases virulence of S. aureus. However, CntK shares only 28% sequence identity with HisR, and their genes exist in different genomic contexts. Knock-out of hisR in F. nucleatum results in a small but reproducible lag in growth compared to wild-type during exponential phase, suggesting that HisR may play a role in growth of this periodontal pathogen.

Porphyromonas gingivalis triggers microglia activation and neurodegenerative processes through NOX4.

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.

Green-synthesized carbon dots from ginger: Multifunctional agents against oral pathogens with biocompatibility in human gingival fibroblast cells

Persistent antibiotic use in treating oral infections often leads to drug resistance in pathogenic bacteria, notably impacting conditions like periodontitis. Addressing this challenge, the study pioneers the use of carbon dots (CDs) synthesized from ginger rhizomes (Zingiber officinale) as a novel biocompatible material. CDs were synthesized via the hydrothermal method, emphasizing a green approach, and comprehensively characterized for their optical properties and structural uniformity. The synthesized CDs showed a zeta potential of −24.9 mV, confirming the formation of stable and well-dispersed particles. Dynamic Light Scattering (DLS) confirmed an average particle size of 2.9 nm, thus validating the formation of CDs. Biomedical assessments demonstrated that the synthesized CDs were non-cytotoxic to human gingival fibroblast cell lines, with effective free radical scavenging activity and high total antioxidant capacity, as indicated by their IC50 values. CDs also exhibited moderate inhibition of protein denaturation compared to the standard. Moreover, they showed significant inhibitory effects against bacterial strains (Pseudomonas aeruginosa, Lactobacillus acidophilus, Escherichia coli, Staphylococcus aureus) and fungal strains (Aspergillus niger, Candida albicans) at minimal concentrations. Notably, CDs inhibited the growth of periodontal pathogens including Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, and Prevotella intermedia. These findings underscore the potential of CDs as multifunctional agents possessing anti-inflammatory, antifungal, antioxidant, and antibacterial properties. Remarkably, they offer a promising alternative to conventional antibiotics, potentially revolutionizing oral healthcare. Their proven biocompatibility and potent bioactivity underscore their innovative potential in biomedical research. Future studies should further assess their efficacy in vivo to fully harness their clinical potential.