Search Results (21)

The oral cavity harbors one of the most diverse microbial ecosystems in the human body, second only to the gut. Periodontitis, a chronic inflammatory disease arising from oral microbiota dysbiosis, has been increasingly associated with systemic disorders such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and neurodegenerative conditions. Although hematogenous dissemination of oral pathogens and inflammatory mediators has long been proposed as a mechanistic link, emerging evidence identifies the oral–gut axis as a novel bidirectional pathway. Swallowed oral pathobionts, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can colonize the gut, disrupt the intestinal barrier, and induce dysbiosis, immune imbalance, and metabolic alterations that aggravate systemic inflammation and disease progression. In contrast, gut dysbiosis, especially in obesity or high-fat-diet models, can exacerbate periodontal tissue destruction through hyperuricemia, altered bone metabolism, and Th17/Treg immune imbalance. Experimental and clinical studies further support this reciprocal relationship, implicating microbial, metabolic, and immune crosstalk in both oral and systemic pathology. Understanding this oral–gut–systemic axis offers a paradigm shift in diagnostics and therapeutics, focusing on precision interventions such as microbiome modulation, probiotics, and integrated oral care to mitigate systemic inflammatory burden and improve overall health outcomes. Full article

In guided bone regeneration (GBR) procedures, d-PTFE membranes are often used as a barrier to promote alveolar ridge regeneration. The aim of this randomized clinical trial was to examine the microbial diversity and structure of biofilms on two types of d-PTFE membranes, Permamem^® and Cytoplast™, over four-week oral cavity exposure periods. Bacterial biofilm analysis was performed using 16S rRNA next-generation sequencing (NGS) on 36 samples (20 Permamem^® and 16 Cytoplast™). The results showed significant differences in the microbial profiles: Cytoplast™ membranes showed reduced microbial diversity and an enhanced proportion of pathobionts like Selenomonas, Segatella, Fusobacterium and Parvimonas, which are associated with periodontal and peri-implant diseases and alveolar bone loss. Permamem^® membranes promoted colonization by bacteria associated with healthy oral conditions, such as the genera Streptococcus, Kingella and Corynebacterium. Overall, our results showed that Cytoplast™ membranes generate a specific type of biofilm, leading to reduction in health-related bacterial species and facilitating growth conditions for dysbiosis shift. Further research and patient follow-ups are essential to thoroughly evaluate the clinical implications of different d-PTFE membranes used in guided bone regeneration. Full article

The interaction between microorganisms in the dental microfilm (plaque) at the gingival margin, the immune system, and the brain is vital for gingival health. The brain constantly receives information regarding microbial composition and inflammation status through afferent nerves and the bloodstream. It modulates immune responses via efferent nerves and hormonal systems to maintain homeostasis. This relationship determines whether the gingiva remains healthy or develops into gingivitis (non-destructive inflammation) or periodontitis (a destructive condition), collectively referred to as periodontal disease. Factors associated with severe periodontitis heighten the responsiveness of this homeostatic system, diminishing the adaptive immune system’s defence against symbiotic microorganisms with pathogenic properties, known as pathobionts. This leads to excessive innate immune system activation, effectively preventing infection but damaging the periodontium. Consequently, investigating the microbiota–brain axis is vital for understanding its impact on periodontal health and disease. Herein, we examine recent advancements in how the defence against pathobionts is organised within the brain, and how it regulates and adapts the pro-inflammatory and anti-inflammatory immune balance, controlling microbiota composition. It also discussed how pathobionts and emotional stress can trigger neurodegenerative diseases, and how inadequate coping strategies for managing daily stress and shift work can disrupt brain circuits linked to immune regulation, weakening the adaptive immune response against pathobionts. Full article

Periodontitis is a prevalent chronic inflammatory disease that has been increasingly recognized for its systemic impacts, including its connection to respiratory diseases such as pneumonia, chronic obstructive pulmonary disease (COPD), Obstructive Sleep Apnea (OSA), asthma, lung cancer, and COVID-19. This review explores the potential role of periodontal pathobionts, particularly Porphyromonas gingivalis (Pg), Treponema denticola (Td), Fusobacterium nucleatum (Fn), Aggregatibacter actinomycetemcomitans (Aa), and Tannerella forsythia (Tf), in respiratory health. These pathobionts contribute to respiratory diseases by facilitating pathogen adhesion, inducing epithelial cell apoptosis, and promoting inflammation. The review also highlights the beneficial effects of periodontal treatment in reducing pathobiont burden and systemic inflammation, thereby mitigating the risk of respiratory complications. This interdisciplinary approach underscores the need to consider oral health as a critical component in managing and preventing respiratory diseases, with future research needed to further clarify these associations and develop targeted interventions. Full article

With increasing life expectancy and an aging population, the demand for dental treatments that preserve natural teeth has grown significantly. Among these treatments, endodontic therapies for pulpitis and apical periodontitis play a vital role, not only in keeping occlusal function, but also in preventing the exacerbation of systemic diseases. Both pulpitis and apical periodontitis are primarily caused by infections of the oral pathobiont within the root canal, leading to inflammation and destruction of the pulp, apical periodontal tissue, and bone. Standard root canal therapy aims to remove the infection source and facilitate natural tissue healing through the body’s regenerative capacity. However, challenges remain, including limited tooth functionality after complete pulp removal in pulpitis and insufficient recovery of the large bone defect in apical periodontitis. To address these limitations, endodontic regenerative therapies have emerged as promising alternatives. Pulp regeneration therapy seeks to restore the functionality of dental pulp, while bone regeneration therapy aims to repair and regenerate large bone defects affected by apical periodontal tissue. Full article

Background: This review synthesizes the role of Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) in modulating immune responses through citrullination and assesses its impact on periodontitis and systemic conditions. Methods: A systematic review was conducted on preclinical and clinical studies focusing on P. gingivalis- and A. actinomycetemcomitans-induced citrullination and its effects on immune responses, particularly inflammatory pathways, and systemic diseases. The search included PubMed, Scopus, Google Scholar, Web of Science, and gray literature. Quality and risk of bias were assessed using OHAT Rob Toll and QUIN-Tool. The review is registered in PROSPERO (ID: CRD42024579352). Results: 18 articles published up to August 2024 were included. Findings show that P. gingivalis and A. actinomycetemcomitans citrullination modulates immune responses, leading to neutrophil dysfunction and chronic inflammation. Key mechanisms include citrullination of antimicrobial peptides, CXCL10, histone H3, α-enolase, and C5a, impairing neutrophil activation and promoting NET formation. Conclusions: This review suggests that P. gingivalis and A. actinomycetemcomitans citrullination modulates immune responses and may influence periodontitis and systemic conditions like RA. Beyond ACPA production, these pathogens affect key proteins such as H3, C5a, and CXCL10, as well as antimicrobial peptides, NET formation, and phagocytosis. These interactions lead to neutrophil dysfunction and potentially affect other cells, subsequently disrupting local and systemic inflammatory responses. Full article

Oral pathobionts are essential in instigating local inflammation within the oral cavity and contribute to the pathogenesis of diseases in the gastrointestinal tract and other distant organs. Among the Gram-negative pathobionts, Porphyromonas gingivalis and Fusobacterium nucleatum emerge as critical drivers of periodontitis, exerting their influence not only locally but also as inducers of gut dysbiosis, intestinal disturbances, and systemic ailments. This dual impact is facilitated by their ectopic colonization of the intestinal mucosa and the subsequent mediation of distal systemic effects by releasing outer membrane vesicles (OMVs) into circulation. This review elucidates the principal components of oral pathobiont-derived OMVs implicated in disease pathogenesis within the oral–gut axis, detailing virulence factors that OMVs carry and their interactions with host epithelial and immune cells, both in vitro and in vivo. Additionally, we shed light on the less acknowledged interplay between oral pathobionts and the gut commensal Akkermansia muciniphila, which can directly impede oral pathobionts’ growth and modulate bacterial gene expression. Notably, OMVs derived from A. muciniphila emerge as promoters of anti-inflammatory effects within the gastrointestinal and distant tissues. Consequently, we explore the potential of A. muciniphila-derived OMVs to interact with oral pathobionts and prevent disease in the oral–gut axis. Full article

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. Full article

This study investigated the impact of tobacco exposure, specifically through heating and burning, on periodontopathogens in the subgingival microbiome among clinically healthy individuals and those diagnosed with periodontitis. The sample comprised 66 subjects (26–56 years, median 38 yrs; 64% females) classified as non-smokers, classic cigarette smokers, and tobacco heating system (THS) smokers (each N = 22). Full-mouth periodontal examination was performed, and 330 paper-point samples from periodontal pockets were collected. Next-generation sequencing of 16S rRNA genes was conducted to identify the composition of subgingival microbiome. Periodontitis prevalence among the groups was ranked as THS (41%) < non-smokers (44%) < cigarette smokers (68%), without statistically significant differences between the groups. The number of perio-pathogenic species was higher in subjects with periodontitis compared to those without (median 7 vs. 6 species; p = 0.005) but without significant differences between exposure groups: non-smokers (6) = smokers (6) < THS (6.5). When combining exposure and periodontal status, each smoker group had more perio-pathogenic species than non-smokers: non-smokers without periodontitis (5) < smokers without periodontitis (5.5) < THS without periodontitis (6); non-smokers with periodontitis (6.5) < THS with periodontitis (7) = smokers with periodontitis (7). Multiple linear regression indicated periodontitis as the sole predictor of perio-pathogenic species quantity, irrespective of the type of tobacco consumption, sex, age, or oral hygiene (R² = 0.163; p = 0.005). In conclusion, the quantity of perio-pathogenic species in the subgingival microbiome was more influenced by periodontitis than by exposure to tobacco smoke, regardless of whether it was heated or burned. Full article

Gynecological and obstetric infectious diseases are crucial to women’s health. There is growing evidence that links the presence of Fusobacterium nucleatum (F. nucleatum), an anaerobic oral commensal and potential periodontal pathogen, to the development and progression of various human diseases, including cancers. While the role of this opportunistic oral pathogen has been extensively studied in colorectal cancer in recent years, research on its epidemiological evidence and mechanistic link to gynecological diseases (GDs) is still ongoing. Thus, the present review, which is the first of its kind, aims to undertake a comprehensive and critical reappraisal of F. nucleatum, including the genetics and mechanistic role in promoting adverse pregnancy outcomes (APOs) and various GDs, including cancers. Additionally, this review discusses new conceptual advances that link the immunomodulatory role of F. nucleatum to the development and progression of breast, ovarian, endometrial, and cervical carcinomas through the activation of various direct and indirect signaling pathways. However, further studies are needed to explore and elucidate the highly dynamic process of host–F. nucleatum interactions and discover new pathways, which will pave the way for the development of better preventive and therapeutic strategies against this pathobiont. Full article

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles. Full article

Periodontitis has been linked to an increased risk of various chronic non-communicable diseases, including gastrointestinal cancers. Indeed, dysbiosis of the oral microbiome and immune-inflammatory pathways related to periodontitis may impact the pathophysiology of the gastrointestinal tract and its accessory organs through the so-called “gum–gut axis”. In addition to the hematogenous spread of periodontal pathogens and inflammatory cytokines, recent research suggests that oral pathobionts may translocate to the gastrointestinal tract through saliva, possibly impacting neoplastic processes in the gastrointestinal, liver, and pancreatic systems. The exact mechanisms by which oral pathogens contribute to the development of digestive tract cancers are not fully understood but may involve dysbiosis of the gut microbiome, chronic inflammation, and immune modulation/evasion, mainly through the interaction with T-helper and monocytic cells. Specifically, keystone periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum, are known to interact with the molecular hallmarks of gastrointestinal cancers, inducing genomic mutations, and promote a permissive immune microenvironment by impairing anti-tumor checkpoints. The evidence gathered here suggests a possible role of periodontitis and oral dysbiosis in the carcinogenesis of the enteral tract. The “gum–gut axis” may therefore represent a promising target for the development of strategies for the prevention and treatment of gastrointestinal cancers. Full article

The pathogenesis of periodontitis depends on a sustained feedback loop where bacterial virulence factors and immune responses both contribute to inflammation and tissue degradation. Periodontitis is a multifactorial disease that is associated with a pathogenic shift in the oral microbiome. Within this shift, low-abundance Gram-negative anaerobic pathobionts transition from harmless colonisers of the subgingival environment to a virulent state that drives evasion and subversion of innate and adaptive immune responses. This, in turn, drives the progression of inflammatory disease and the destruction of tooth-supporting structures. From an evolutionary perspective, bacteria have developed this phenotypic plasticity in order to respond and adapt to environmental stimuli or external stressors. This review summarises the available knowledge of genetic, transcriptional, and post-translational mechanisms which mediate the commensal-pathogen transition of periodontal bacteria. The review will focus primarily on Porphyromonas gingivalis. Full article

Periodontal disease is a chronic oral inflammatory disorder initiated by pathobiontic bacteria found in dental plaques—complex biofilms on the tooth surface. The disease begins as an acute local inflammation of the gingival tissue (gingivitis) and can progress to periodontitis, which eventually leads to the formation of periodontal pockets and ultimately results in tooth loss. The main problem in periodontology is that the diagnosis is based on the assessment of the already obvious tissue damage. Therefore, it is necessary to improve the current diagnostics used to assess periodontal disease. Using lipidomic analyses, we show that both crucial periodontal pathogens, Porphyromonas gingivalis and Tannerella forsythia, synthesize ceramide phosphoethanolamine (CPE) species, membrane sphingolipids not typically found in vertebrates. Previously, it was shown that this particular lipid can be specifically detected by an aegerolysin protein, erylysin A (EryA). Here, we show that EryA can specifically bind to CPE species from the total lipid extract from P. gingivalis. Furthermore, using a fluorescently labelled EryA-mCherry, we were able to detect CPE species in clinical samples of dental plaque from periodontal patients. These results demonstrate the potential of specific periodontal pathogen-derived lipids as biomarkers for periodontal disease and other chronic inflammatory diseases. Full article

For the treatment of periodontitis stage III/IV, a quadrant/week-wise debridement (Q-SRP) was compared with three full-mouth approaches: full-mouth scaling (FMS, accelerated Q-SRP within 24 h), full-mouth scaling with chlorhexidine-based disinfection (FMD), and FMD with adjuvant erythritol air polishing (FMDAP). The objective of this prospective, randomized study (a substudy of ClinicalTrials.gov, identifier: NCT03509233) was to compare the clinical and microbiological effects of the treatments. In total, 105 patients were randomized to one of the four aforementioned treatment groups, with n = 25, 28, 27, and 25 patients allocated to each group, respectively. At baseline and 3 and 6 months after treatment, the clinical parameters, including the pocket probing depths, clinical attachment level, and bleeding on probing, were recorded, and the prevalence of the total bacteria and four periodontal pathobionts (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia) was determined using real-time quantitative PCR. Concerning the clinical outcomes, all the treatment modalities were effective, but the full-mouth approaches, especially FMDAP, were slightly superior to Q-SRP. Using the FMD approach, the reduction in the bacterial load and the number of pathobionts was significantly greater than for FMS, followed by Q-SRP. FMDAP was the least effective protocol for microbial reduction. However, after a temporary increase 3 months after therapy using FMDAP, a significant decrease in the key pathogen, P. gingivalis, was observed. These findings were not consistent with the clinical results from the FMDAP group. In conclusion, the dynamics of bacterial colonization do not necessarily correlate with clinical outcomes after full-mouth treatments for periodontitis stage III/IV. Full article