Interconnection of periodontal disease and comorbidities: Evidence, mechanisms, and implications

Periodontology 2000, Год журнала: 2022, Номер 89(1), С. 9 - 18

Опубликована: Март 4, 2022

Abstract Periodontitis, a microbiome‐driven inflammatory disease of the tooth‐attachment apparatus, is epidemiologically linked with other disorders, including cardio‐metabolic, cognitive neurodegenerative and autoimmune diseases, respiratory infections, certain cancers. These associations may, in part, be causal, as suggested by interventional studies showing that local treatment periodontitis reduces systemic inflammation surrogate markers comorbid diseases. The potential cause‐and‐effect connection between comorbidities corroborated preclinical models disease, which additionally provided mechanistic insights into these associations. This overview discusses recent advances our understanding periodontitis‐systemic connection, may potentially lead to innovative therapeutic options reduce risk periodontitis‐linked comorbidities.

Язык: Английский

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Fusobacterium nucleatum and cancer

Periodontology 2000, Год журнала: 2022, Номер 89(1), С. 166 - 180

Опубликована: Март 4, 2022

Abstract Accumulating evidence demonstrates that the oral pathobiont Fusobacterium nucleatum is involved in progression of an increasing number tumors types. Thus far, mechanisms underlying tumor exacerbation by F. include enhancement proliferation, establishment a tumor‐promoting immune environment, induction chemoresistance, and activation checkpoints. This review focuses on mediate tumor‐specific colonization fusobacteria. Elucidating mediating fusobacterial tropism promotion might provide new insights for development novel approaches detection treatment.

Язык: Английский

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Oral polymicrobial communities: Assembly, function, and impact on diseases

Cell Host & Microbe, Год журнала: 2023, Номер 31(4), С. 528 - 538

Опубликована: Март 17, 2023

Язык: Английский

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F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production

EBioMedicine, Год журнала: 2023, Номер 88, С. 104444 - 104444

Опубликована: Янв. 27, 2023

Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of in shaping OSCC microenvironment remains elusive.We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum progression. Xenograft tumor model, metabolic screening RNA sequencing were performed elucidate mechanisms pro-tumor role nucleatum.We show that a major protumorigenic bacterium, nucleatum, accumulates invasive margins tissues drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows OSCC-resident triggers GalNAc-Autophagy-TBC1D5 signaling, leading GLUT1 aggregation plasma membrane deposition extracellular lactate. Simultaneous functional inhibition GalNAc efficiently reduces TAMs formation restrains progression.These findings suggest tumor-resident affects immunomodulatory via modulating glycolysis lactate deposition. targeted intervention this process could provide distinct strategy patients advanced OSCC.This work was supported by National Natural Science Foundation China Key Program Projects (82030070, LC) Distinguished Young Scholars (31725011, LC), as well Innovation Team Project Hubei Province (2020CFA014, LC).

Язык: Английский

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Fusobacterium nucleatum in tumors: from tumorigenesis to tumor metastasis and tumor resistance

Cancer Biology & Therapy, Год журнала: 2024, Номер 25(1)

Опубликована: Янв. 30, 2024

Fusobacterium nucleatum, an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role cancer progression and prognosis. While extensive research revealed mechanistic links between nucleatum colorectal cancer, a comprehensive review spanning presence metastatic implications cancers beyond origin is conspicuously absent. This paper broadens our perspective from to various malignancies associated with including oral, pancreatic, esophageal, breast, gastric cancers. Our central focus unravel mechanisms governing colonization, initiation, promotion of metastasis across diverse types. Additionally, we explore nucleatum's adverse impacts on therapies, particularly within domains immunotherapy chemotherapy. Furthermore, this underscores clinical significance as potential tumor biomarker therapeutic target, offering novel outlook applicability detection prognostic assessment.

Язык: Английский

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Periodontitis and risk of cancer: Mechanistic evidence

Periodontology 2000, Год журнала: 2023, Номер 96(1), С. 83 - 94

Опубликована: Дек. 15, 2023

Abstract This review aims to critically analyze the pathways of interaction and pathogenic mechanisms linking periodontitis oral bacteria with initiation/progression cancer at different body compartments. A higher risk head neck has been consistently associated periodontitis. relationship explained by local promotion dysbiosis, chronic inflammation, immune evasion, direct (epi)genetic damage epithelial cells periodontal pathobionts their toxins. Epidemiological reports have also studied a possible link between incidence other malignancies distant sites, such as lung, breast, prostate, digestive tract cancers. Mechanistically, involved, including induction systemic inflammatory state spreading carcinogenic potential. Indeed, may promote low‐grade inflammation phenotypic changes in mononuclear cells, leading release free radicals cytokines, well extracellular matrix degradation, which are all involved metastatic processes. Moreover, transient hematogenous spill out or micro‐aspiration/swallowing virulence factors (i.e., lipopolysaccharides, fimbriae), lead non‐indigenous bacterial colonization multiple microenvironments. These events turn replenish tumor‐associated microbiome thus influence molecular hallmarks cancer. Particularly, specific strains (e.g., Porphyromonas gingivalis Fusobacterium nucleatum ) translocate through enteral routes, being implicated esophageal, gastric, pancreatic, colorectal tumorigenesis modulation gastrointestinal antitumor system tumor‐infiltrating T cells) increased expression pro‐inflammatory/oncogenic genes. Ultimately, potential common factors, relevant comorbidities, upstream drivers, gerovulnerability diseases, explaining cannot be disregarded. The evidence analyzed here emphasizes relevance stimulates future research endeavors.

Язык: Английский

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The interplay between Helicobacter pylori and the gut microbiota: An emerging driver influencing the immune system homeostasis and gastric carcinogenesis

Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12

Опубликована: Авг. 15, 2022

The human gut microbiota are critical for preserving the health status because they required digestion and nutrient acquisition, development of immune system, energy metabolism. microbial composition is greatly influenced by colonization recalcitrant pathogen Helicobacter pylori ( H. ) conventional antibiotic regimens that follow. considered to be main microorganism in gastric carcinogenesis, it appears early stages process. However, a non- profile also suggested, primarily later tumorigenesis. On other hand, specific groups microbes may produce beneficial byproducts such as short-chain fatty acids (acetate, butyrate, propionate) can modulate inflammation tumorigenesis pathways. In this review, we aim present how influences population modify host immunity trigger carcinogenesis. We will highlight effect on immunotherapeutic approaches checkpoint blockade cancer treatment perspective further innovative therapeutic paradigms prevent progression -induced stomach cancer.

Язык: Английский

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Biological biomarkers of oral cancer

Periodontology 2000, Год журнала: 2023, Номер 96(1), С. 250 - 280

Опубликована: Дек. 10, 2023

The oral squamous cell carcinoma (OSCC) 5 year survival rate of 41% has marginally improved in the last few years, with less than a 1% improvement per from 2005 to 2017, higher rates when detected at early stages. Based on histopathological grading dysplasia, it is estimated that severe dysplasia malignant transformation 7%-50%. Despite these numbers, does not reliably predict its clinical behavior. Thus, more accurate markers predicting progression cancer would enable better targeting lesions for closer follow-up, especially stages disease. In this context, molecular biomarkers derived genetics, proteins, and metabolites play key roles oncology. These signatures can help likelihood OSCC development and/or have potential detect disease an stage and, support treatment decision-making responsiveness. Also, identifying reliable detection be obtained non-invasively enhance management OSCC. This review will discuss emerged different biological areas, including genomics, transcriptomics, proteomics, metabolomics, immunomics, microbiomics.

Язык: Английский

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Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach

Vaccines, Год журнала: 2023, Номер 11(3), С. 525 - 525

Опубликована: Фев. 23, 2023

Colorectal cancer (CRC) is one of the most common cancers and second-highest in cancer-related deaths worldwide. The changes gut homeostasis microbial dysbiosis lead to initiation tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nucleatum are principal contributors induction pathogenesis CRC. Thus, inhibiting growth survival these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) an essential membrane protein F. that promotes adherence bacterium colon cells, recruitment immune tumorigenesis. present study depicts design silico vaccine candidate comprising B-cell T-cell epitopes Fap2 for improving cell-mediated humoral responses against Notably, this participates significant protein-protein interactions with human Toll-like receptors, especially TLR6 reveals, which likely correlated its efficacy eliciting potential responses. immunogenic trait designed was verified by simulation approach. cDNA construct cloned within expression vector pET30ax expression. Collectively, proposed may serve as promising therapeutic intervening nucleatum-induced

Язык: Английский

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The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review

Pathogens, Год журнала: 2024, Номер 13(1), С. 93 - 93

Опубликована: Янв. 20, 2024

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

Язык: Английский

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