The biology of cancer is characterized by an intricate interplay of cells originating not only from the tumor mass, but also its surrounding environment. Different microbial species have been suggested to be enriched in tumors and the impacts of these on tumor phenotypes is subject to intensive investigation. For these efforts, model systems that accurately reflect human-microbe interactions are rapidly gaining importance. Here we present a guide for selecting a suitable in vitro co-culture platform used to model different cancer-microbiome interactions. Our discussion spans a variety of in vitro models, including 2D cultures, tumor spheroids, organoids, and organ-on-a-chip platforms, where we delineate their respective advantages, limitations, and applicability in cancer microbiome research. Particular focus is placed on methodologies that facilitate the exposure of cancer cells to microbes, such as organoid microinjections and co-culture on microfluidic devices. We highlight studies offering critical insights into possible cancer-microbe interactions and underscore the importance of in vitro models in those discoveries. We anticipate the integration of more complex microbial communities and the inclusion of immune cells into co-culture systems to more accurately simulate the tumor microenvironment. The advent of ever more sophisticated co-culture models will aid in unraveling the mechanisms of cancer-microbiome interplay and contribute to exploiting their potential in novel diagnostic and therapeutic strategies.

This narrative review explores the multifaceted links between periodontal diseases (gingivitis and periodontitis) and systemic health conditions, including cardiovascular disease, diabetes, adverse pregnancy outcomes, Alzheimer's disease, cancers, rheumatoid arthritis, and respiratory infections. It aims to synthesize evidence on how local oral infections exert systemic effects and evaluate the potential of diagnostic technologies to monitor these interactions.

This narrative review synthesizes current scientific literature on periodontal disease pathogenesis, focusing on key pathogens (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum) and their roles in driving local and systemic inflammation via virulence factors and microbial dysbiosis. It examines biomarker-based diagnostic approaches (e.g., IL-1β, TNF-α, microbial DNA) in saliva, blood, and gingival crevicular fluid (GCF) and evaluates current and emerging diagnostic tools (e.g., ELISA, PCR, lateral flow assays, biosensors, microfluidics).

The review highlights that periodontal pathogens contribute to systemic disease through complex mechanisms including persistent inflammation (driven by cytokines like IL-1β, TNF-α), endotoxemia (via LPS, noting pathogen-specific structural variations impacting immune response), molecular mimicry, and immune modulation. Current diagnostic methods provide valuable information but often face limitations in speed, portability, and multiplexing capability needed for comprehensive point-of-care assessment. Emerging technologies, particularly multiplex platforms integrating biosensors or microfluidics, demonstrate significant potential for rapid, user-friendly analysis of multiple biomarkers, facilitating earlier detection and personalized risk stratification, especially in high-risk populations.

Periodontal diseases significantly impact systemic health via intricate microbial and inflammatory pathways. The complexity of these interactions necessitates moving beyond conventional diagnostics towards integrated, advanced technologies. Implementing rapid, multiplex biomarker detection platforms within a multidisciplinary healthcare framework holds the potential to revolutionize early detection of linked conditions, improve personalized management strategies, and ultimately reduce the systemic burden of periodontal disease.

Cancers of the oral cavity, lip, salivary gland, and oropharynx cause substantial global disease burden. While tobacco-use and alcohol use are highly associated with oral cancers, the rising incidence of disease in patients who do not use tobacco or alcohol points to additional carcinogenic risk factors. Chronic inflammation, disruption of the oral microbiome, and dysbiosis are becoming more widely implicated in the pathogenesis of oral cancer. Several studies have identified specific bacterial species enriched in patients with oral cancer, including Porphyromonas gingivalis and Fusobacterium nucleatum. In this narrative review, we describe potential carcinogenic mechanisms exhibited by these species and other microbes in the development of oral cancer.

Periodontal disease (PD) is an inflammatory condition that can contribute to the development of oral cancer. Chronic inflammation from PD can lead to the release of inflammatory mediators and growth factors that promote tumorigenesis. Porphyromonas gingivalis (P. gingivalis) is one of several pathogens implicated in PD and its potential link to oral cancer. However, other viral infections, such as human cytomegalovirus (HCMV), can also contribute to chronic inflammation, creating a favorable environment for oral cancer development.

The present literature review tries to investigate the possible influence of P. gingivalis and HCMV co-infection in fostering the development of oral cancer and chronic periodontitis.

A comprehensive search was conducted in PubMed and Google Scholar, focusing on the relevance and significance of articles that examine the role of P. gingivalis and HCMV in periodontal disease and oral cancer.

The evidence suggests that P. gingivalis and HCMV may act synergistically to modulate host immunity, disrupt epithelial integrity, and interfere with key cellular pathways. These interactions may enhance tissue destruction and foster a microenvironment conducive to malignant transformation. However, most of these findings stem from in vitro models and small-scale clinical studies, limiting the generalizability and clinical relevance of current conclusions.

Although the proposed interaction between P. gingivalis and HCMV provides a compelling framework for understanding how microbial co-infections may influence oral cancer, the evidence remains preliminary and largely associative. To support these mechanistic hypotheses, future studies should give top priority to in vivo models, bigger patient cohorts, and longitudinal clinical studies.

Adjunctive use of photodynamic therapy in combination with scaling and root planing for periodontal maintenance offers an alternative to antibiotic therapy, potentially mitigating the risk of antibiotic resistance and its genotoxic or mutagenic effects. This systematic review analyzed studies, as of January 2023, that included the effects of a single application of photodynamic therapy in residual periodontal pockets with the probing depth and clinical attachment level as the primary and secondary outcomes, respectively.

PubMed, Scopus, and Web of Science databases, as well as the US National Institutes of Health and WHO Clinical Trials Registry, were searched for eligible studies on January 14, 2023.

Excluding non-English language articles, a total of nine studies examining 286 subjects were considered. Six of the nine studies resulted in decreased probing depth levels. Likewise, six of the nine studies exhibited a positive trend in terms of clinical attachment levels with photodynamic therapy. A limited number of studies revealed significant probing depth levels and clinical attachment levels after photodynamic therapy. The overall risk of bias was high in four studies, four studies showed some concerns regarding the study limitations, and one study had a low risk of bias.

Photodynamic therapy in combination with scaling and root planing may result in modest reductions in residual periodontal pocket depth levels and improvements in clinical attachment levels. The use of PDT in periodontal maintenance can reduce or eliminate the need for periodontal surgery, which may be more invasive and lead to a longer recovery time.

As per the recent research findings, there is a significant difference between the bacteriome of normal tissue (NT) and tumor tissues (TT) of oral squamous cell carcinoma (OSCC). Identifying this distinct bacteriome is crucial for understanding their potential contribution to oral carcinogenesis. This systematic review (SR) aims to identify exclusive and relative bacterial abundance and bacterial diversity in TT and NT.

The review was conducted following the PRISMA guidelines. PUBMED and SCOPUS databases were searched for studies in English published till 31st August 2024. The inclusion criteria focused on identifying bacteriome in NT versus TT at either species,/genus, and/or phylum level through 16 s ribosomal RNA sequencing. Quality assessment was performed using an eleven-parameter tool combining the Newcastle-Ottawa Scale and customized criteria.

Evaluating the selected 13 articles, we have identified the exclusive and relative abundance of bacteriome in TT and NT at phylum, genus, and species levels. Three phyla such as Chloroflexota, Deinococcus-Thermus, and Mycoplasmatota, are found exclusively in TT. Seven genus such as Eubacterium, Campylobacter, Aeromonas, Oceanivigra, Rheinheimera, Weissella, and Catonella are exclusively found in TT. Ten species such as Micrococcus luteus, Prevotella melaninogenica, Exiguobacterium oxidotolerans, Fusobacterium naviforme, Staphylococcus aureus, Veillonella parvula, Parvimonas sp oral taxon 110, Eubacterium II G1 infirmum, Eubacterium XI G3 Brachy, Weissella viridescens are found in TT. Six genus such as Capnocytophaga, Selenomonas, Leptothrix, Desulfovibrio, Desulfoplanes, Pelospora are found exclusively in NT. Eleven species, such as Streptococcus sp. Oral taxon 071,Selenomonas sputigena, Treponema pedis, Acholeplasmatales bacterium, Capnocytophaga haemolytica, Eubacterium sp., Syntrophomonadaceae genomosp.,Treponema putidum, Mitsuokella sp., Actinomyces sp. Oral taxon 848 str. F0332, p- 2534 - 18B5-gut-group are found in NT. Seven common genera within which different species are identified in TT and NT, suggesting differences in bacterial behaviour and characteristics within the same genus. A total of 12 phyla, 35 genera, and 54 species were found to be relatively more abundant in TT compared to NT. Conversely, 7 phyla, 32 genera, and 45 species were relatively more abundant in NT than in TT. Considerable variations in diversity metrics were found between TT and NT.

This systematic review is the first to identify a distinct bacteriome exclusive to OSCC tumour tissue compared to normal tissue using 16S ribosomal RNA sequencing. This pioneering work lays the foundation for future studies on the oral microbiome as a potential diagnostic or therapeutic target in oral cancer management. It emphasizes the importance of exploring species-level differences for a deeper understanding of their roles in OSCC.

Not applicable.

Matrix metalloproteinases (MMPs) are key enzymes involved in extracellular matrix (ECM) remodeling, regulating a wide range of cellular and immune processes in both homeostatic and pathological conditions. Host-microbiota interactions play a critical role in maintaining ECM balance; however, during dysbiosis, this regulation is disrupted, leading to compromised barrier integrity, pathogen translocation into circulation, and the development of systemic diseases and cancer. This review highlights the bidirectional relationship between MMP expression/activity and microbiota dysbiosis, emphasizing tissue-specific alterations in MMP activity that contribute to disease progression. In addition, it integrates interdisciplinary evidence to illustrate the MMP-dependent mechanisms underlying various pathologies associated with oral and gut microbiome dysbiosis, including long-range effects through the gut-skin and gut-brain axes. Thus, this review introduces the emerging field of MatrixBiome, which explores the complex interactions between the ECM, microbiota, and host tissues. Finally, it also outlines therapeutic strategies to modulate MMP levels, either indirectly through microbiome-targeted approaches (e.g., prebiotics, probiotics, and postbiotics) or directly using MMP inhibitors, offering promising avenues for future clinical interventions.

Pancreatic cancer, one of the most lethal malignancies, remains challenging due to late diagnosis, aggressive progression, and therapeutic resistance. Recent advances have revealed the presence of intratumoral microbiota, predominantly originating from the oral and gut microbiomes, which play pivotal roles in pancreatic cancer pathogenesis. The dynamic interplay between oral and gut microbial communities, termed the "oral-gut microbiota axis," contributes multifacetedly to pancreatic ductal adenocarcinoma (PDAC). Microbial translocation via anatomical or circulatory routes establishes tumor-resident microbiota, driving oncogenesis through metabolic reprogramming, immune regulation, inhibition of apoptosis, chronic inflammation, and dysregulation of the cell cycle. Additionally, intratumoral microbiota promote chemoresistance and immune evasion, further complicating treatment outcomes. Emerging evidence highlights microbial signatures in saliva and fecal samples as promising non-invasive diagnostic biomarkers, while microbial diversity correlates with prognosis. Therapeutic strategies targeting this axis-such as antibiotics, probiotics, and engineered bacteria-demonstrate potential to enhance treatment efficacy. By integrating mechanisms of microbial influence on tumor biology, drug resistance, and therapeutic applications, the oral-gut microbiota axis emerges as a critical regulator of PDAC, offering novel perspectives for early detection, prognostic assessment, and microbiome-based therapeutic interventions.

Cancer continues to be the leading cause of mortality worldwide, with metastasis being the primary contributor to cancer-related deaths. Despite significant advancements in cancer therapies, metastasis remains a major challenge in effective cancer management. Metastasis, the process by which cancer cells spread from the primary tumor to distant organs, is a complex phenomenon influenced by multiple factors, including the human microbiota. The human body encompasses various microorganisms, comprising bacteria, viruses, fungi, and protozoa, collectively known as microbiota. In fact, the microbiota is more abundant than human cells, and its disruption, leading to an imbalance in host-microbiota interactions (dysbiosis), has been linked to various diseases, including cancer. Among all microbiota, bacteria are one of the key contributors to cancer progression. Bacteria and bacteria-derived components such as secondary metabolites, QSPs, and toxins play a pivotal role in the metastatic progression of cancers. This review explores the intricate relationship between the human microbiota and cancer progression, focusing on different bacterial species which have been implicated in tumorigenesis, immune evasion, and metastasis. The present review explores the role of the human microbiome, specifically of bacteria in promoting metastasis in different types of cancers, demonstrating its ability to impact both the spread of tumors and their underlying mechanisms. This review also highlights the therapeutic potential and challenges of microbiome-based interventions in combating metastatic cancers. By addressing these challenges and by integrating microbiome-targeted strategies into clinical cancer treatment could represent a transformative approach in the fight against metastasis.

Targeted therapy represents a form of cancer treatment that specifically focuses on molecular markers regulating the growth, division, and dissemination of cancer cells. It serves as the cornerstone of precision medicine and is associated with fewer adverse effects compared to conventional chemotherapy, thus enhancing the quality of patient survival. These make targeted therapy as a vital component of contemporary anti-cancer strategies. Although targeted therapy has achieved excellent anti-cancer results, there are still many factors affecting its efficacy. Among the numerous factors affecting anti-cancer treatment, the role of intestinal bacteria and its metabolites are becoming increasingly prominent, particularly in immunotherapy. However, their effects on anticancer targeted therapy have not been systematically reviewed. Herein, we discuss the crosstalk between gut bacteria and anticancer targeted therapies, while also highlighting potential therapeutic strategies and future research directions.

This study aimed to identify periodontal pathogens involved in the onset and progression of OSCC.

Saliva samples were collected from 112 patients without oral mucosal diseases (OMDs) as controls; 36 patients with oral potentially malignant disorders (OPMDs); and 104 patients with OSCC. Periodontal examinations were performed on all patients. Endpoint PCR was performed for seven species of oral pathogens. The 16S rRNA analysis was performed using 20 DNA samples from each group.

Periodontitis tended to worsen in the OMDs group compared to the control group. The number of oral bacteria was significantly higher in the OSCC group than in the other groups. The detection rates of P. gingivalis and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) were significantly higher in the OSCC group than those in the control group. From 16S rRNA analysis, the relative abundance of Prevotella buccae and intermedia was significantly higher in OSCC than in the control. Moreover, LPS derived from P. gingivalis contributes to the early development of oral epithelial precancerous lesions and carcinomas in mice.

Specific periodontal pathogens are present in the oral cavities of patients with OPMDs and OSCC, and changes in the bacterial flora due to their presence may contribute to the onset and progression of OMDs.

Epithelial barriers serve as critical defense lines against microbial infiltration and maintain tissue homeostasis. E-cadherin, an essential component of adherens junctions, has emerged as a pivotal molecule that secures epithelial homeostasis. Lately, its pleiotropic role beyond barrier function, including its involvement in immune responses, has become more evident. Herein, we delve into the intricate relationship between (dys)regulation of epithelial homeostasis and the versatile functionality of E-cadherin, describing complex mechanisms that underlie barrier integrity and disruption in disease pathogenesis such as bacterial infection and inflammation, among others. Clinical implications of E-cadherin perturbations in host pathophysiology are emphasized; downregulation, proteolytic phenomena, abnormal localization/signaling and aberrant immune reactions are linked with a broad spectrum of pathology beyond infectious diseases. Finally, potential therapeutic interventions that may harness E-cadherin to mitigate barrier-associated tissue damage are explored. Overall, this review highlights the crucial role of E-cadherin in systemic health, offering insights that could pave the way for strategies to reinforce/restore barrier integrity and treat related diseases.

Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer's disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly Porphyromonas gingivalis, has garnered significant attention. P. gingivalis, a major driver of periodontitis, is recognized for its potential systemic effects and its putative role in AD pathogenesis. This review examines evidence connecting P. gingivalis to hallmark AD features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, and other neuropathological features consistent with AD. Virulence factors, such as gingipains and lipopolysaccharides, were shown to be implicated in blood-brain barrier disruption, neuroinflammation, and neuronal damage. P. gingivalis-derived outer membrane vesicles may serve to disseminate virulence factors to brain tissues. Indirect mechanisms, including systemic inflammation triggered by chronic periodontal infections, are also supposed to exacerbate neurodegenerative processes. While the exact pathways remain uncertain, studies detecting P. gingivalis virulence factors and its other components in AD-affected brains support their possible role in disease pathogenesis. This review underscores the need for further investigation into P. gingivalis-mediated mechanisms and their interplay with host responses. Understanding these interactions could provide critical insights into novel strategies for reducing AD risk through periodontal disease management.

There is growing evidence suggesting a strong association between members of the oral microbiota and various types of cancer, including oral cancer, colorectal cancer, esophageal squamous cell carcinoma, and pancreatic cancer. Periodontal diseases closely associated with pathogenic bacteria in the oral cavity have been shown to be correlated with the occurrence and development of cancers. Among the periodontal disease-associated bacteria in the oral cavity, two prominent oral pathogens, Porphyromonas gingivalis and Fusobacterium nucleatum, have been found to promote tumor cell proliferation, invasion, and migration, as well as to inhibit immune cell function, thereby facilitating tumor progression. The presence of other oral pathogenic bacteria, such as Treponema denticola, Tannerella forsythia, Parvimonas micra, and Aggregatibacter actinomycetemcomitans, has also been found to be associated with cancer worsening. Oral commensal bacteria play a crucial role in maintaining the normal oral homeostasis. However, the relationship between oral commensal bacteria and the occurrence and development of cancers remains controversial. Some studies suggest an increase in oral commensal bacteria during tumor development, while others suggest an association of certain commensal bacteria with lower tumor risk. The microbiota can significantly alter responses and toxicity to various forms of cancer treatment through interactions with the human body, thereby influencing disease progression. In this chapter, we provide a concise overview of current understanding of the role of the oral microbiota in cancer.

Oral squamous cell carcinoma (OSCC) is a prevalent oral malignancy, which poses significant health risks with a high mortality rate. Regulatory T cells (Tregs), characterized by their immunosuppressive capabilities, are intricately linked to OSCC progression and patient outcomes. The metabolic reprogramming of Tregs within the OSCC tumor microenvironment (TME) underpins their function, with key pathways such as the tryptophan-kynurenine-aryl hydrocarbon receptor, PI3K-Akt-mTOR and nucleotide metabolism significantly contributing to their suppressive activities. Targeting these metabolic pathways offers a novel therapeutic approach to reduce Treg-mediated immunosuppression and enhance anti-tumor responses. This review explores the metabolic dependencies and pathways that sustain Treg function in OSCC, highlighting key metabolic adaptations such as glycolysis, fatty acid oxidation, amino acid metabolism and PI3K-Akt-mTOR signaling pathway that enable Tregs to thrive in the challenging conditions of the TME. Additionally, the review discusses the influence of the oral microbiome on Treg metabolism and evaluates potential therapeutic strategies targeting these metabolic pathways. Despite the promising potential of these interventions, challenges such as selectivity, toxicity, tumor heterogeneity, and resistance mechanisms remain. The review concludes with perspectives on personalized medicine and integrative approaches, emphasizing the need for continued research to translate these findings into effective clinical applications for OSCC treatment.

Heterogeneous cancers that lack strong driver mutations with high penetrance, such as head and neck squamous cell carcinoma (HNSCC), present unique challenges to understanding their aetiology due to the complex interactions between genetics and environmental factors. The interplay between lifestyle factors (such as poor oral hygiene, smoking, or alcohol consumption), the oral and gut microbiome, and host genetics appears particularly important in the context of HNSCC. The complex interplay between the gut microbiota and cancer treatment outcomes has also received increasing attention in recent years. This review article describes the bidirectional communication between the host and the oral/gut microbiome, focusing on microbiome-derived metabolites and their impact on systemic immune responses and the modulation of the tumour microenvironment. In addition, we review the role of host lifestyle factors in shaping the composition of the oral/gut microbiota and its impact on cancer progression and therapy. Overall, this review highlights the rationality of considering the oral/gut microbiota as a critical determinant of cancer therapy outcomes and points to therapeutic opportunities offered by targeting the oral/gut microbiota in the management of HNSCC.

To characterize the oral microbiome of patients with head and neck squamous cell carcinoma (HNSCC) before and during radiotherapy (RT), compared to healthy individuals. Evaluating the impact of oral microbiome in the clinical outcomes one year following the end of RT.

Oral samples were collected from HNSCC patients who underwent RT using the following regimens: no dose received (T0), dose 12-16 Gy (T1), dose 30-36 Gy (T2) and dose ≥ 60 Gy (T3). Samples from healthy individuals were also collected only once as a control group. Regions V1-V2 of the 16S rRNA were sequenced by Illumina and analyzed using Mothur.

49 patients with HNSCC and 25 healthy individuals were included. At T0, HNSCC patients showed a lower abundance of Firmicutes and Streptococcus (p = 0.011, p = 0.002) and a higher abundance of Bacteroidetes (p = 0.005) compared to healthy individuals. During RT, Fusobacterium (p = 0.017) and Porphyromonas (p = 0.0008) decreased, while Streptococcus increased at T1 (p = 0.001). By T3, the differences in Firmicutes, Bacteroidetes, and Streptococcus between the control and HNSCC groups were no longer significant (p > 0.3). Patients with higher initial abundances of Porphyromonas (p = 0.012) and Fusobacterium (p = 0.017) had poorer outcomes, including recurrence, metastasis, and death. In contrast, disease-free patients had a higher abundance of Streptococcus (p = 0.004).

Oral microbiome dysbiosis was found in HNSCC patients. By the end of RT, the main initial differences in phylum and genus abundance observed at T0 between the control and HNSCC groups were no longer present. Higher abundances of Fusobacterium and Porphyromonas were associated with poor outcomes.

Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host's immune system, activate cell invasion and proliferation, possess anti-apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement.

Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research has highlighted the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between the microbiome and esophageal carcinogenesis, focusing on the following eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target the microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.

Oral squamous cell carcinoma (OSCC) is the predominant form of head and neck cancer, often diagnosed at late stages, resulting in a poor prognosis. Recent studies indicate a potential association between OSCC and microbial presence. Microorganisms have been identified in various tumors and lesions, including OSCC and oral potentially malignant disorders (OPMDs). Intralesional microbiota are considered important components of the tumor microenvironment (TME) and may contribute to carcinogenesis.

Sources were collected through thorough searches of databases PubMed and Embase. The review focused on microbial characteristics, potential origins, and their impact on cancer progression.

Bacteria display varying abundance and diversity throughout the stages of OSCC and OPMDs. Intraleisional bacteria may have diverse sources, including not only oral plaque and saliva but also potentially the gut. Intralesional bacteria have both pro-carcinogenic and anti-carcinogenic effects, affecting processes like cell proliferation, invasion, and immune response.

Intralesional microbiota are crucial in OSCC and OPMDs, influencing both disease progression and treatments. Despite their significance, challenges like inconsistent sampling and microbial identification remain. Future research is required to fully understand their role and improve clinical applications.

Periodontitis is a severe gum infection that begins as gingivitis and can lead to gum recession, bone loss, and tooth loss if left untreated. It is primarily caused by bacterial infection, which triggers inflammation and the formation of periodontal pockets. Notably, periodontitis is associated with systemic health issues and has been linked to heart disease, diabetes, respiratory diseases, adverse pregnancy outcomes, and cancers. Accordingly, the presence of chronic inflammation and immune system dysregulation in individuals with periodontitis significantly contributes to the initiation and progression of various cancers, particularly oral cancers. These processes promote genetic mutations, impair DNA repair mechanisms, and create a tumor-supportive environment. Moreover, the bacteria associated with periodontitis produce harmful byproducts and toxins that directly damage the DNA within oral cells, exacerbating cancer development. In addition, chronic inflammation not only stimulates cell proliferation but also inhibits apoptosis, causes DNA damage, and triggers the release of pro-inflammatory cytokines. Collectively, these factors play a crucial role in the progression of cancer in individuals affected by periodontitis. Further, specific viral and bacterial agents, such as hepatitis B and C viruses, human papillomavirus (HPV), Helicobacter pylori (H. pylori), and Porphyromonas gingivalis, contribute to cancer development through distinct mechanisms. Bacterial infections have systemic implications for cancer development, while viral infections provoke immune and inflammatory responses that can lead to genetic mutations. This review will elucidate the link between periodontitis and cancers, particularly oral cancers, exploring their underlying mechanisms to provide insights for future research and treatment advancements.

An association between periodontal disease and oral squamous cell carcinoma (OSCC) has been recognized. However, there is no causal relationship between the two. The polymicrobial etiology of periodontal disease is confirmed, and so are the proven etiological factors for OSCC. Inflammation lies at the core of periodontal pathogenesis induced by the putative microbes. OSCC has inflammatory overtures in its pathobiology. Bacterial species involved in periodontal disease have been extensively documented and validated. The microbial profile in OSCC has been explored with no specific conclusions. The scientific reasoning to link a common microbial signature that connects periodontal disease to OSCC has led to many studies but has not provided conclusive evidence. Therefore, it would be beneficial to know the status of any plausible microbiota having a similarity in periodontal disease and OSCC. This brief review attempted to clarify the existence of a dysbiotic "fingerprint" that may link these two diseases. The review examined the literature with a focused objective of identifying periodontal microbial profiles in OSCC that could provide insights into pathogen commonality. The review concluded that there is great diversity in microbial association, but important bacterial species that correlate with periodontal disease and OSCC are forthcoming.

The impact of gut and oral microbiota on the clinical outcomes of patients with oral squamous cell carcinoma (OSCC) is unknown. We compared the bacterial composition of dental plaque and feces between patients with OSCC and healthy controls (HCs). Fecal and dental plaque samples were collected from 7 HCs and 18 patients with OSCC before treatment initiation. Terminal restriction fragment-length polymorphism analysis of 16S rRNA genes was performed. Differences in bacterial diversity between the HC and OSCC groups were examined. We compared the occupancy of each bacterial species in samples taken from patients with OSCC and HCs and analyzed the correlation between PD-L1 expression in the tumor specimens and the occupancy of each bacterial species. The gut and oral microbiota of patients with OSCC were more varied than those of HCs. Porphyromonas and Prevotella were significantly more abundant in patients with OSCC than in HCs. The abundance of Clostridium subcluster XIVa in the gut microbiota of the PD-L1-positive group was significantly greater than that in the PD-L1-negative group. The oral and gut microbiomes of patients with OSCC were in a state of dysbiosis. Our results suggest the possibility of new cancer therapies targeting these disease-specific microbiomes using probiotics and synbiotics.

Periodontitis is linked to the onset and progression of oral squamous cell carcinoma (OSCC), an epidemiologically frequent and clinically aggressive malignancy. In this context, Fusobacterium (F.) nucleatum and Porphyromonas (P.) gingivalis, two bacteria that cause periodontitis, are found in OSCC tissues as well as in oral premalignant lesions, where they exert pro-tumorigenic activities. Since the two bacteria are present also in endodontic diseases, playing a role in their pathogenesis, here we analyze the literature searching for information on the impact that endodontic infection by P. gingivalis or F. nucleatum could have on cellular and molecular events involved in oral carcinogenesis. Results from the reviewed papers indicate that infection by P. gingivalis and/or F. nucleatum triggers the production of inflammatory cytokines and growth factors in dental pulp cells or periodontal cells, affecting the survival, proliferation, invasion, and differentiation of OSCC cells. In addition, the two bacteria and the cytokines they induce halt the differentiation and stimulate the proliferation and invasion of stem cells populating the dental pulp or the periodontium. Although most of the literature confutes the possibility that bacteria-induced endodontic inflammatory diseases could impact on oral carcinogenesis, the papers we have analyzed and discussed herein recommend further investigations on this topic.

Aggregatibacter actinomycetemcomitans is an opportunistic Gram-negative periodontopathogen strongly associated with periodontitis and infective endocarditis. Recent evidence suggests that periodontopathogens can influence the initiation and progression of oral squamous cell carcinoma (OSCC). Herein we aimed to investigate the effect of A. actinomycetemcomitans-derived extracellular vesicles (EVs) on OSCC cell behavior compared with EVs from periodontopathogens known to associate with carcinogenesis. EVs were isolated from: A. actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; Porphyromonas gingivalis; Fusobacterium nucleatum; and Parvimonas micra. The effect of EVs on primary and metastatic OSCC cells was assessed using cell proliferation, apoptosis, migration, invasion, and tubulogenesis assays. A. actinomycetemcomitans-derived EVs reduced the metastatic cancer cell proliferation, invasion, tubulogenesis, and increased apoptosis, mostly in CDT- and LPS O-antigen-dependent manner. EVs from F. nucleatum impaired the metastatic cancer cell proliferation and induced the apoptosis rates in all OSCC cell lines. EVs enhanced cancer cell migration regardless of bacterial species. In sum, this is the first study demonstrating the influence of A. actinomycetemcomitans-derived EVs on oral cancer in comparison with other periodontopathogens. Our findings revealed a potential antitumorigenic effect of these EVs on metastatic OSCC cells, which warrants further in vivo investigations.

The oral cavity harbors a diverse microbiota that plays a significant role in maintaining homeostasis. Disruption of this balance can lead to various oral diseases, including periodontitis. Accumulating evidence suggests a connection between periodontitis and extra-oral diseases such as cardiovascular disease, rheumatoid arthritis, obesity, and diabetes. During periodontitis, oral bacteria enter the bloodstream directly, impacting extra-oral organs. Furthermore, recent studies have uncovered another pathway, the direct oral-gut axis, where oral bacteria translocate to the gut through an enteral route, influencing gut microbiota and metabolism. Oral pathobionts associated with exacerbation of periodontal disease are implicated in gut pathology, including inflammatory bowel disease and colorectal cancer through ectopic gut colonization. Furthermore, oral bacteria can provoke host immune responses, leading to colitis and other inflammatory diseases. Conversely, mechanisms by which extra-oral conditions exacerbate oral diseases, such as periodontitis, are also beginning to be elucidated. This review discusses the bidirectional interrelationship between oral and systemic diseases based on the oral-gut linkage.

Periodontal disease is a risk factor for head and neck squamous cell carcinoma (HNSCC), and Porphyromonas gingivalis, a major periodontal pathogen, has been identified as a specific and potentially independent microbial factor that increases the risk of cancer mortality. Gene expression in HNSCC due to P. gingivalis infection and how changes in gene expression affect the prognosis of HNSCC patients are not clarified. When P. gingivalis was cultured with HNSCC cells, it efficiently adhered to these cells and enhanced their invasive ability. A transcriptome analysis of P. gingivalis -infected HNSCC cells showed that genes related to migration, including CCL20, CITED2, CTGF, C8orf44-SGK3, DUSP10, EGR3, FUZ, HBEGF, IL1B, IL24, JUN, PLAU, PTGS2, P2RY1, SEMA7A, SGK1 and SIX2, were highly up- or down-regulated. The expression of up-regulated genes was examined using the expression data of HNSCC patients obtained from The Cancer Genome Atlas (TCGA) database, and the expression of 5 genes, including PLAU, was found to be higher in cancer tissue than in solid normal tissue. An analysis of protein-protein interactions revealed that these 5 genes formed a dense network. A Cox regression analysis showed that high PLAU expression levels were associated with a poor prognosis in patients with TCGA-HNSCC. Furthermore, the prognostic impact correlated with tumour size and the presence or absence of lymph node metastasis. Collectively, these results suggest the potential of PLAU as a molecular prognostic marker in HNSCC patients. Further in vivo and in vitro studies are needed to verify the findings of this study.

Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.

Expression of programmed death ligand-1 (PD-L1) is related to the prognosis of many solid malignancies, including oral squamous cell carcinoma (OSCC), but the mechanism of PD-L1 induction remains obscure. In this study, we examined the expression of PD-L1 and partial epithelial-mesenchymal transition (pEMT) induced by bacterial lipopolysaccharide (LPS) in OSCC.

The expression of Toll-like receptor 4 (TLR4) recognizing LPS in OSCC cell lines was analyzed. Moreover, the induction of PD-L1 expression by Porphyromonas gingivalis (P.g) or Escherichia coli (E. coli) LPS and EMT was analyzed by western blotting and RT-PCR. Morphology, proliferation, migration, and invasion capacities were examined upon addition of LPS. PD-L1 within EXOs was examined.

PD-L1 expression and pEMT induced by LPS of P.g or E. coli in TLR4-expressing OSCC cell lines were observed. Addition of LPS did not change migration, proliferation, or cell morphology, but increased invasive ability. Moreover, higher expression of PD-L1 was observed in OSCC EXOs with LPS.

Oral bacterial LPS is involved in enhanced invasive potential in OSCC cells, causing PD-L1 expression and induction of pEMT. The enhancement of PD-L1 expression after addition of LPS may be mediated by EXOs.

Head and neck cancer (HNC) is the seventh most prevalent malignancy worldwide in 2020. Cancer metastasis is the main cause of poor prognosis in HNC patients. Recently, circular RNAs (circRNAs), initially thought to have no biological function, are attracting increasing attention, and their crucial roles in mediating HNC metastasis are being extensively investigated. Existing studies have shown that circRNAs primarily function through miRNA sponges, transcriptional regulation, interacting with RNA-binding proteins (RBPs) and as translation templates. Among these functions, the function of miRNA sponge is the most prominent. In this review, we summarized the reported circRNAs involved in HNC metastasis, aiming to elucidate the regulatory relationship between circRNAs and HNC metastasis. Furthermore, we summarized the latest advances in the epidemiological information of HNC metastasis and the tumor metastasis theories, the biogenesis, characterization and functional mechanisms of circRNAs, and their potential clinical applications. Although the research on circRNAs is still in its infancy, circRNAs are expected to serve as prognostic markers and effective therapeutic targets to inhibit HNC metastasis and significantly improve the prognosis of HNC patients.

Oral squamous cell carcinoma (OSCC) is the most common oral cavity malignancy associated with multiple risk factors. In the last 14 years, oral dysbiosis has attracted the scientific community's attention as a potential oncogenic factor, in parallel with the development of omics technologies that have revolutionized microbiological research. The present umbrella review aimed to investigate the oral microbiological content (bacilli, viruses, and fungi) of tissue and saliva samples from adult (>18 years) patients with OSCC. The secondary objective was to compare the oral microbiome of OSCC subjects with non-OSCC subjects. The study protocol was under the PRISMA statement and registered on PROSPERO (CRD42023448153). Data from 32 systematic reviews were extracted, qualitatively summarized, and analyzed using AMSTAR-2. An increase in oral bacteria of the phylum Fusobacteria, Proteobacteria, and Bacteroidetes and a decrease in Firmicutes and Actinobacteria were observed in OSCC patients. The increased bacterial genera were periodontopathogens. The most common viruses were EBV and HPV, especially the high-risk genotypes. Candida was the most studied oral fungus and was always increased in OSCC subjects. Further studies should investigate the possible carcinogenic mechanisms of oral microorganisms found increased in tissue samples and saliva from adult subjects with OSCC.

The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.

Head and neck cancer (HNSCC) is a heterogeneous group of cancers, affecting multiple regions such as oral cavity, pharynx, larynx, and nasal region, each showing a distinct molecular profile. HNSCC accounts for more than 6 million cases worldwide, soaring mainly in the developing countries.

The aetiology of HNSCC is complex and multifactorial, involving both genetic and environmental factors. The critical role of microbiome, which includes bacteria, viruses, and fungi, is under spotlight due to the recent reports on their contribution in the development and progression of HNSCC. This review focuses on the effect of opportunistic pathogens on the host genome and epigenome, which contributes to the disease progression. Drawing parallels from the host-pathogen interactions observed in other tumour types arising from the epithelial tissue such as colorectal cancer, the review also calls attention to the potential explorations of the role of pathogens in HNSCC biology and discusses the clinical implications of microbiome research in detection and treatment of HNSCC.

Our understanding of the genomic effects of the microbes on the disease progression and the mechanistic insights of the host-pathogen interaction will pave way to novel treatment and preventive approaches in HNSCC.

Background: Since the discovery of PCR and ELISA, in vitro research in the realm of molecular biology pertaining to oral squamous cell carcinoma (OSCC) has witnessed significant expansion. Objective: to provide a comprehensive overview of molecular biology research on OSCC through visual mapping techniques. Methods: We conducted an analysis of publications within the "oral squamous cell carcinoma" category from Scopus' core collection. On 20 January 2023, we screened these publications using an advanced search employing the keywords "oral squamous cell cancer" and "cell line." Data analysis was performed using Microsoft Excel 2010 and VOSviewer, facilitating the examination of author contributions, journal productivity, institutional affiliations, and contributions by nations. VOSviewer was further utilized for co-occurrence and reference analysis of keywords. Results: A total of 781 papers spanning from 1992 to 2023 were collected. Notably, Japan, China, and the United States emerged as significant contributors in this field. The Osaka University Graduate School of Dentistry (Japan) ranked first with 21 publications. Chae J-I of Chonbuk National University (South Korea) emerged as the most prolific author, with 14 publications. The International Journal of Oncology and the Journal of Oral Pathology and Medicine were identified as the two most prolific journals. The central themes that emerged were epidermal growth factor receptor, invasion, epithelial-mesenchymal transition, angiogenesis, apoptosis, and metastasis. Conclusion: The rate of publications focused on the molecular biology of OSCC has seen a remarkable increase. Research priorities have shifted from topics such as "radiation, RANKL, cyclin D1, RNA interference, and matrix metalloproteinase" to encompass areas such as "chemoresistance due to cisplatin, other therapeutic agents (metformin and monoclonal antibody), autophagy, inflammation, microRNA, cancer-associated fibroblasts, and STAT3 (with roles in cell migration and tumorigenesis)." These seven significant future research areas hold promise in identifying reliable biological markers for oral cancer detection and treatment, thereby improving clinical outcomes.

The tumor microbiome, a relatively new research field, affects tumor progression through several mechanisms. The Cancer Microbiome Atlas (TCMA) database was recently published. In the present study, we used TCMA and The Cancer Genome Atlas and examined microbiome profiling in head and neck squamous cell carcinoma (HNSCC), the role of the intratumoral microbiota in the prognosis of HNSCC patients, and differentially expressed genes in tumor cells in relation to specific bacterial infections. We investigated 18 microbes at the genus level that differed between solid normal tissue (n = 22) and primary tumors (n = 154). The tissue microbiome profiles of Actinomyces, Fusobacterium, and Rothia at the genus level differed between the solid normal tissue and primary tumors of HNSCC patients. When the prognosis of groups with rates over and under the median for each microbe at the genus level was examined, rates for Leptotrichia which were over the median correlated with significantly higher overall survival rates. We then extracted 35 differentially expressed genes between the over- and under-the-median-for-Leptotrichia groups based on the criteria of >1.5 fold and p < 0.05 in the Mann-Whitney U-test. A pathway analysis showed that these Leptotrichia-related genes were associated with the pathways of Alzheimer disease, neurodegeneration-multiple diseases, prion disease, MAPK signaling, and PI3K-Akt signaling, while protein-protein interaction analysis revealed that these genes formed a dense network. In conclusion, probiotics and specific antimicrobial therapy targeting Leptotrichia may have an impact on the prognosis of HNSCC.

Red ginseng is an herb with many medicinal properties and aids as a mouth rinse with fewer side effects than chlorhexidine.

The study aimed to compare the efficacy of red ginseng herbal mouth rinses with those of chlorhexidine and saline in oral cancer patients.

The present pilot study was a double-blinded randomized control trial with 45 histopathologically diagnosed oral squamous cell carcinoma patients divided into three groups: two intervention groups (herbal and chlorhexidine mouth rinse) and one control group (saline). Saliva samples for each patient were collected at baseline and after 14 days of using the mouth rinses. A microbiological examination of salivary samples was done by analysing total oral bacterial load along with specific counts for Porphyromonas gingivalis and Fusobacterium nucleatum at baseline and after the usage of mouth rinse.

The data normality was analysed using the Shapiro-Wilk test, and following the normal distribution of data, parametric tests were employed. Paired t-test and one-way analysis of variance, followed by post hoc Bonferroni test, were used for inter-group and intra-group differences.

There was a significant mean difference in total colony count, Fusobacterium nucleatum, and Porphyromonas gingivalis with oral hygiene index and gingival index improvement in the red ginseng herbal mouth rinse group when compared to the chlorhexidine and saline groups.

In this study, red ginseng mouth rinse exhibited an increased antibacterial effect compared to chlorhexidine and saline. Hence, red ginseng mouth rinse can be used in oral cancer patients to maintain oral health, thereby improving the prognosis of these patients.

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.

Epithelial cells line mucosal surfaces such as in the gingival crevice and provide a barrier to the ingress of colonizing microorganisms. However, epithelial cells are more than a passive barrier to microbial intrusion, and rather constitute an interactive interface with colonizing organisms which senses the composition of the microbiome and communicates this information to the underlying cells of the innate immune system. Microorganisms, for their part, have devised means to manipulate host cell signal transduction pathways to favor their colonization and survival. Study of this field, which has become known as cellular microbiology, has revealed much about epithelial cell physiology, bacterial colonization and pathogenic strategies, and innate host responses.

The microbial community structure in saliva differs at different altitudes. However, the impact of acute high-altitude exposure on the oral microbiota is unclear. This study explored the impact of acute high-altitude exposure on the salivary microbiome to establish a foundation for the future prevention of oral diseases. Methods. Unstimulated whole saliva samples were collected from 12 male subjects at the following three time points: one day before entering high altitude (an altitude of 350 m, pre-altitude group), seven days after arrival at high altitude (an altitude of 4,500 m, altitude group) and seven days after returning to low altitude (an altitude of 350 m, post-altitude group). Thus, a total of 36 saliva samples were obtained. 16S rRNA V3-V4 region amplicon sequencing was used to analyze the diversity and structure of the salivary microbial communities, and a network analysis was employed to investigate the relationships among salivary microorganisms. The function of these microorganisms was predicted with a Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis.

In total, there were 756 operational taxonomic units (OTUs) identified, with 541, 613, and 615 OTUs identified in the pre-altitude, altitude, and post-altitude groups, respectively. Acute high-altitude exposure decreased the diversity of the salivary microbiome. Prior to acute high-altitude exposure, the microbiome mainly consisted of Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria. After altitude exposure, the relative abundance of Streptococcus and Veillonella increased, and the relative abundance of Prevotella, Porphyromonas, and Alloprevotella decreased. The relationship among the salivary microorganisms was also affected by acute high-altitude exposure. The relative abundance of carbohydrate metabolism gene functions was upregulated, while the relative abundance of coenzyme and vitamin metabolism gene functions was downregulated.

Rapid high-altitude exposure decreased the biodiversity of the salivary microbiome, changing the community structure, symbiotic relationships among species, and abundance of functional genes. This suggests that the stress of acute high-altitude exposure influenced the stability of the salivary microbiome.

During recent years, considerable progress has been made in understanding the etiopathogenesis of periodontitis in its various forms and their interactions with the host. Furthermore, a number of reports have highlighted the importance of oral health and disease in systemic conditions, especially cardiovascular diseases and diabetes. In this regard, research has attempted to explain the role of periodontitis in promoting alteration in distant sites and organs. Recently, DNA sequencing studies have revealed how oral infections can occur in distant sites such as the colon, reproductive tissues, metabolic diseases, and atheromas. The objective of this review is to describe and update the emerging evidence and knowledge regarding the association between periodontitis and systemic disease and to analyse the evidence that has reported periodontitis as a risk factor for the development of various forms of systemic diseases in order to provide a better understanding of the possible shared etiopathogenetic pathways between periodontitis and the different forms of systemic diseases.

Electronic cigarette (EC) usage or vaping has seen a significant rise in recent years across various parts of the world. They have been publicized as a safe alternative to smoking; however, this is not supported strongly by robust research evidence. Toxicological analysis of EC liquid and aerosol has revealed presence of several toxicants with known carcinogenicity. Oral cavity is the primary site of exposure of both cigarette smoke and EC aerosol. Role of EC in oral cancer is not as well-researched as that of traditional smoking. However, several recent studies have shown that it can lead to a wide range of potentially carcinogenic molecular events in oral cells. This review delineates the oral carcinogenesis potential of ECs at the molecular level, providing a summary of the effects of EC usage on cancer therapy resistance, cancer stem cells (CSCs), immune evasion, and microbiome dysbiosis, all of which may lead to increased tumor malignancy and poorer patient prognosis. This review of literature indicates that ECs may not be as safe as they are perceived to be, however further research is needed to definitively determine their oncogenic potential.

This systematic review aims to investigate possible connections between the oral microbiome and the onset and carcinogenesis of oral epithelial dysplasia (OED).

A systematic search was performed on PubMed, Embase, Cochrane Database, and SCOPUS by two authors independently, addressing the focused question- "Has oral microbiome dysbiosis been involved in the onset and carcinogenesis of oral epithelial dysplasia?" We used the Newcastle-Ottawa scale to assess the quality of studies included in the review.

Out of 580 references screened, ten studies were found eligible for inclusion. All studies were case-control studies, and only qualitative analysis was conducted due to heterogeneous characteristics. The overall risk of bias in the eligible studies was considered as high. Microbiome diversity indices showed inconsistent evidence among studies. A significant increase of phylum Bacteroidetes in OED patients was reported in five studies. Five studies reported an increase of genus Fusobacterium in both the OED and oral squamous cell carcinoma (OSCC) patients and six different studies respectively reported a reduction of genus Streptococcus in both the OED and OSCC groups when compared to normal controls. Other predominant bacteria that were specific to different patient groups varied in each study.

The results of the included studies showed that the composition of the oral microbiome in patients with OED compared to healthy controls and OSCC patients was inconsistent. However, all ten studies showed non-negligible heterogeneity in the type and size of the sample, and the comparability between groups, which strongly limited the external validity of results. Further studies are strongly recommended.

Innate immunity serves as the frontline to combat invading pathogens. Oral microbiota is the total collection of microorganisms colonized within the oral cavity. By recognizing the resident microorganisms through pattern recognition receptors, innate immunity is capable of interacting with oral microbiota and maintaining homeostasis. Dysregulation of interaction may lead to the pathogenesis of several oral diseases. Decoding the crosstalk between oral microbiota and innate immunity may be contributory to developing novel therapies for preventing and treating oral diseases.

This article reviewed pattern recognition receptors in the recognition of oral microbiota, the reciprocal interaction between innate immunity and oral microbiota, and discussed how the dysregulation of this relationship leads to the pathogenesis and development of oral diseases.

Many studies have been conducted to illustrate the relationship between oral microbiota and innate immunity and its role in the occurrence of different oral diseases. The impact and mechanisms of innate immune cells on oral microbiota and the mechanisms of dysbiotic microbiota in altering innate immunity are still needed to be investigated. Altering the oral microbiota might be a possible solution for treating and preventing oral diseases.

The Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays a crucial role in immune evasion and inhibition of apoptosis in host cells and has the potential to cause cancer. However, its structure has not yet been characterized. We used an in-silico approach to determine the 3D structure of the P. gingivalis NDK. Furthermore, structural characterization and functional annotation were performed using computational approaches. The 3D structure of NDK was predicted through homology modeling. The structural domains predicted for the model protein belong to the NDK family. Structural alignment of prokaryotic and eukaryotic NDKs with the model protein revealed the conservation of the domain region. Structure-based phylogenetic analysis depicted a significant evolutionary relationship between the model protein and the prokaryotic NDK. Functional annotation of the model confirmed structural homology, exhibiting similar enzymatic functions as NDK, including ATP binding and nucleoside diphosphate kinase activity. Furthermore, molecular dynamic (MD) simulation technique stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.