References (Periodontal Disease and Cancer)

Ahn, J., Segers, S., & Hayes, R. B. Periodontal disease, Porphyromonas gingivalis serum antibody levels and orodigestive cancer mortality. Carcinogenesis 33, 5 (2012). doi:10.1093/carcin/bgs112.
Clinically ascertained periodontitis and serum IgG levels against P. gingivalis were associated with increased orodigestive cancer mortality, particularly colorectal and possibly pancreatic cancers, suggesting P. gingivalis as a biomarker for microbe-associated cancer risk.

Ahn, S. H., Chun, S. M., Park, C., Lee, J. H., Lee, S. W., & Lee, T. H. Transcriptome profiling analysis of senescent gingival fibroblasts in response to Fusobacterium nucleatum infection. PLoS ONE 12, e0188755 (2017). https://doi.org/10.1371/journal.pone.0188755.
Aged gingival fibroblasts exhibit impaired defense and inflammatory responses to F. nucleatum, revealing age-dependent susceptibility to periodontal infections and highlighting potential targets for age-specific interventions.

Al Asqah, M., Al Hamoudi, N., Anil, S., et al. Is the presence of Helicobacter pylori in the dental plaque of patients with chronic periodontitis a risk factor for gastric infection? Canadian Journal of Gastroenterology 23, 3 (2009). doi:10.1155/2009/950527
Patients with chronic periodontitis harbored higher levels of H. pylori in dental plaque and the stomach, suggesting the oral cavity may act as a reservoir, with potential implications for gastric infection and reinfection.

Al-Nawas, B., Grötz, K.A. Prospective study of the long term change of the oral flora after radiation therapy. Support Care Cancer 14, 195–202 (2006).
Long-term follow-up after radiotherapy in head and neck cancer patients showed persistent periodontal pathogen presence, indicating high risk for oral infections despite hygiene interventions.

Alnuaimi, A. D., Wiesenfeld, D., O'Brien-Simpson, N. M., Reynolds, E. C. & McCullough, M. J. Oral Candida colonization in oral cancer patients and its relationship with traditional risk factors of oral cancer: a matched case-control study. Oral Oncol. 51, 1062–1068 (2015). doi:10.1016/j.oraloncology.2014.11.008.
Study of 52 oral cancer patients and matched controls revealed higher oral Candida carriage in cancer patients. Alcohol consumption and high Candida colonization were significant risk factors, and genotype differences of C. albicans may contribute to oral carcinogenesis.

Amar, S., Leeman, S. Periodontal innate immune mechanisms relevant to obesity. Molecular Oral Microbiology 28, 291–301 (2013). doi:10.1111/omi.12035.
Obesity exacerbates periodontal disease by modulating host immune responses. This review explores the interactions between obesity-related inflammation and P. gingivalis infection, highlighting the impact of metabolic status on periodontal pathogen susceptibility and disease severity.

Amit Kumar, Pragna Lakshmi Thotakura, Basant Kumar Tiwary, Ramadas Krishna. Target identification in Fusobacterium nucleatum by subtractive genomics approach and enrichment analysis of host-pathogen protein-protein interactions. BMC Microbiol 16, 117 (2016). doi:10.1186/s12866-016-0700-0.
F. nucleatum, a periodontal pathogen, may enhance colorectal cancer progression through modulation of host inflammatory responses, oncogene activation, and suppression of DNA repair mechanisms, highlighting potential druggable targets for therapeutic intervention.

Ampomah, N. K., Teles, F., Martin, L. M., Lu, J., Koestler, D. C., Kelsey, K. T., Beck, J. D., Platz, E. A., & Michaud, D. S. Circulating IgG antibodies to periodontal bacteria and lung cancer risk in the CLUE cohorts. JNCI Cancer Spectrum 7, 3 (2023); doi:10.1093/jncics/pkad029. Investigates serum IgG antibodies to 13 periodontal bacteria and lung cancer risk. Some antibodies, such as to Prevotella intermedia, Actinomyces naeslundii, and Veillonella parvula, were inversely associated with lung cancer, suggesting immune surveillance may modulate cancer risk. A positive association with Porphyromonas gingivalis highlights the pathogen-specific effects.

Anand, S., Kaur, H., & Mande, S. S. Comparative in silico analysis of butyrate production pathways in gut commensals and pathogens. Front. Microbiol. 7, 1945 (2016). doi:10.3389/fmicb.2016.01945
A genomic analysis compared butyrate biosynthesis pathways in gut commensals and pathogens. While commensals primarily use pyruvate fermentation, pathogens like Fusobacterium utilize amino acid-based pathways, producing harmful by-products. Oral pathogens (Porphyromonas and Filifactor) retain both pathways, reflecting butyrate’s cytotoxic role in oral diseases. These insights can guide therapeutic or probiotic interventions targeting microbial butyrate metabolism.

Atanasova, K.R., Yilmaz, Ö. Prelude to oral microbes and chronic diseases: Past, present and future. Microbes Infect. 17, 507–518 (2015). doi:10.1016/j.micinf.2015.03.007.
Oral pathogens such as P. gingivalis and F. nucleatum are implicated not only in periodontal disease but in systemic conditions including cancer, diabetes, and rheumatoid arthritis, highlighting their central role in chronic disease pathogenesis.

Baima, G., et al. Can periodontitis affect the health and disease of the digestive system? A comprehensive review of epidemiological evidence and biological mechanisms. Curr. Oral Health Rep. 8, 45–61 (2021). https://doi.org/10.1007/s40496-021-00302-9.
Evidence supports the “gum-gut axis,” where periodontitis and oral pathogens may influence gastrointestinal disease and cancers, including colorectal, esophageal, and pancreatic cancers.

Baima, G., Ribaldone, D. G., Romano, F., Aimetti, M. & Romandini, M. The Gum–Gut Axis: Periodontitis and the Risk of Gastrointestinal Cancers. Cancers 15, 10.3390/cancers15184594 (2023). Dysbiosis of the oral microbiome, including Porphyromonas gingivalis and Fusobacterium nucleatum, may affect gastrointestinal carcinogenesis through the “gum–gut axis.” Pathogens can translocate via saliva or the bloodstream, promoting inflammation, genomic mutations, and immune evasion, highlighting a potential target for cancer prevention strategies.

Bapat, R. A., Bedia, S. V., Bedia, A. S., Yang, H. J., Dharmadhikari, S., Abdulla, A. M., Chaubal, T. V., Bapat, P. R., Abullais, S. S., Wahab, S., Kesharwani, P. Current appraises of therapeutic applications of nanocurcumin: A novel drug delivery approach for biomaterials in dentistry. Environmental Research 238, 116971 (2023). doi:10.1016/j.envres.2023.116971.
Curcuma longa-derived curcumin suffers from poor bioavailability, prompting the development of nanocurcumin (nCur). This narrative review outlines its antibacterial, anti-inflammatory, and anticancer effects, particularly against oral pathogens (S. mutans, P. gingivalis, E. faecalis), and evaluates its potential to improve clinical outcomes in oral diseases such as periodontitis, dental caries, and oral lichen planus.

Bommareddy, P. K., Mrinal, B. K., Depass, A. L. Antibacterial and anti-proliferative activity of isolated fractions of aqueous extract from the rhubarb stem. FASEB J. 27, S1 (2013). doi:10.1096/fasebj.27.1_supplement.lb582.
This study identifies a carbohydrate fraction from rhubarb stem with broad-spectrum antibacterial activity against periodontal pathogen Aggregatibacter actinomycetemcomitans and anti-proliferative effects on breast cancer cells, suggesting potential therapeutic applications with low cytotoxicity.

Boonyaleka, K., Okano, T., Iida, T. et al. Fusobacterium nucleatum infection activates the noncanonical inflammasome and exacerbates inflammatory response in DSS-induced colitis. Eur. J. Immunol. 53, 11 (2023). https://doi.org/10.1002/eji.202350455.
This study demonstrates that F. nucleatum infection in mice exacerbates colitis by activating caspase-11-mediated pyroptosis and IL-1β release. It reveals how this periodontal pathogen can modulate immune responses and drive inflammation in distant organs, illustrating its systemic impact.

Bourgeois, D., Inquimbert, C., Ottolenghi, L. & Carrouel, F. Periodontal pathogens as risk factors of cardiovascular diseases, diabetes, rheumatoid arthritis, cancer, and chronic obstructive pulmonary disease—Is there cause for consideration? Microorganisms 7, 424 (2019). doi:10.3390/microorganisms7100424.
Review discussing the potential role of periodontal pathogens as risk factors in multiple noncommunicable diseases, including cancer, and emphasizing preventive strategies despite the lack of clear causality.

Bu, T., Lan, J., Jo, I., et al. Structural basis of the inhibition of L-methionine γ-lyase from Fusobacterium nucleatum. International Journal of Molecular Sciences 24, 2 (2023). doi:10.3390/ijms24021651
The study elucidates the crystal structure of Fn1419, a hydrogen sulfide-producing enzyme in F. nucleatum, and identifies gallic acid and dihydromyricetin as selective inhibitors. This provides a molecular basis for targeted therapeutic development against pathogenic F. nucleatum.

Buetas, E., Jordán-López, M., López-Roldán, A., et al. Impact of Periodontitis on the Leakage of Oral Bacteria to the Gut. Journal of Dental Research 103, 3 (2024). doi:10.1177/00220345231221709.
Investigating oral-to-gut bacterial translocation, this study found minimal leakage of oral bacteria to the gut in both healthy and periodontitis individuals, suggesting periodontal pathogens could serve as biomarkers for gastrointestinal disorders.

Buetas, E., Jordán-López, M., López-Roldán, A., Mira, A., & Carda-Diéguez, M. Impact of Periodontitis on the Leakage of Oral Bacteria to the Gut. Journal of Dental Research 103, 3 (2024). doi:10.1177/00220345231221709
This study analyzes oral-to-gut bacterial translocation in healthy and periodontitis individuals, finding limited leakage and no enrichment of periodontal pathogens in feces. Oral bacteria could serve as biomarkers for gastrointestinal disorders.

Bui, F. Q., Almeida-da-Silva, C. L. C., Huynh, B. et al. Association between periodontal pathogens and systemic disease. Biomed. J. 42, 1 (2019). https://doi.org/10.1016/j.bj.2018.12.001.
This review explores evidence linking periodontitis to systemic disorders including cardiovascular disease, colorectal cancer, diabetes, Alzheimer’s disease, and adverse pregnancy outcomes. The authors focus on how periodontal pathogens and their metabolic by-products modulate immune responses beyond the oral cavity, potentially contributing to disease development.

Bullon, P., Pavillard, L. E., & de la Torre-Torres, R. Inflammasome and Oral Diseases. Experientia Suppl. 108, 123–141 (2018). https://doi.org/10.1007/978-3-319-89390-7_7.
Inflammasome activation contributes to oral inflammatory conditions including periodontitis, candidiasis, and oral cancer, linking local molecular processes to systemic disease susceptibility.

C., C., Geng, F., Shi, X., et al. The prevalence rate of periodontal pathogens and its association with oral squamous cell carcinoma. Appl. Microbiol. Biotechnol. 103, 3 (2019).
This study shows that P. gingivalis and F. nucleatum are enriched in oral squamous cell carcinoma tissues, with correlations to late-stage cancer, low differentiation, and lymph node metastasis, indicating that periodontal pathogens may contribute to oral carcinogenesis.

Carl, W. Oral complications of local and systemic cancer treatment. Curr. Opin. Oncol. 7, 4 (1995); doi:10.1097/00001622-199507000-00005. Details therapy-related oral complications, including mucositis, which can exacerbate periodontal disease and facilitate microbial invasion in cancer patients.

Chang, C., Geng, F., Shi, X., et al. The prevalence rate of periodontal pathogens and its association with oral squamous cell carcinoma. Applied Microbiology and Biotechnology 103, 3 (2019). doi:10.1007/s00253-018-9475-6
Analysis of OSCC patient tissues revealed enrichment of P. gingivalis and F. nucleatum, linking periodontal pathogens to tumor tissue colonization. Infection correlated with late-stage disease, poor differentiation, and lymph node metastasis, supporting a role in oral carcinogenesis.

Chen, M.F., Lu, M.S., Hsieh, C.C., & Chen, W.C. Porphyromonas gingivalis promotes tumor progression in esophageal squamous cell carcinoma. Cellular Oncology 44, 281–296 (2021). https://doi.org/10.1007/s13402-020-00573-x.
Oral infection with P. gingivalis increases EsoSCC risk, promotes epithelial-mesenchymal transition, IL-6–mediated tumor growth, and recruitment of myeloid-derived suppressor cells in vitro and in vivo.

Chen, Y., Chen, X., Yu, H., et al. Oral microbiota as promising diagnostic biomarkers for gastrointestinal cancer: A systematic review. OncoTargets and Therapy 12, 2019. doi:10.2147/OTT.S230262.
This review summarized evidence that oral microbiota, particularly periodontal pathogens like Porphyromonas gingivalis and Tannerella forsythia, may serve as early noninvasive biomarkers for gastrointestinal cancers. Differences in microbiota profiles between upper and lower digestive tract cancers were noted, emphasizing anatomical influences on microbial-cancer interactions.

Chen, Y., Huang, Z., Tang, Z. et al. More than just a periodontal pathogen – research progress on Fusobacterium nucleatum. Front. Cell. Infect. Microbiol. 12, 815318 (2022). https://doi.org/10.3389/fcimb.2022.815318.
This review details the multifaceted role of F. nucleatum, a common oral opportunistic bacterium, in periodontal diseases, halitosis, dental pulp infection, oral cancer, and systemic disorders. It synthesizes recent findings on epidemiology, pathogenic mechanisms, and therapeutic strategies, underlining the bacterium’s significant contribution to both oral and systemic health.

Cho, B.H., Jung, Y.H., Kim, D.J., Woo, B.H., Jung, J.E., Lee, J.H., Choi, Y.W., Park, H.R. Acetylshikonin suppresses invasion of Porphyromonas gingivalis-infected YD10B oral cancer cells by modulating the interleukin-8/matrix metalloproteinase axis. Mol. Med. Rep. 17, 1875–1884 (2018). doi:10.3892/mmr.2017.8151.
Acetylshikonin, a flavonoid with anti-inflammatory properties, inhibited the invasiveness of oral cancer cells infected with the periodontal pathogen P. gingivalis by suppressing IL-8–dependent MMP release, suggesting potential for both preventive and therapeutic use in oral cancer associated with chronic periodontal infection.

Claudio Passariello, Dario Di Nardo, Marco Seracchiani, et al. Harnessing the power of biologic agents on the oral microbiota: A way to promote oral and systemic health? J Contemp Dent Pract 21, 1125–1133 (2021). doi:10.5005/JP-JOURNALS-10024-2949.
Oral dysbiosis, including overgrowth of pathobionts like P. gingivalis, A. actinomycetemcomitans, and F. nucleatum, is implicated in periodontal disease and systemic comorbidities. Biologic agents and microbiome modulation may restore oral-systemic health balance.

Cong, S., Tong, Q., Peng, Q., et al. In vitro anti-bacterial activity of diosgenin on Porphyromonas gingivalis and Prevotella intermedia. Molecular Medicine Reports 22, 6 (2020). doi:10.3892/mmr.2020.11620.
Diosgenin, a natural steroidal sapogenin, exhibits dose-dependent inhibition of P. gingivalis and P. intermedia, both in planktonic and biofilm forms, suggesting potential as a natural agent for periodontitis prevention and therapy.

Cong, S., Tong, Q., Peng, Q., Shen, T., Zhu, X., Xu, Y., & Qi, S. In vitro anti-bacterial activity of diosgenin on Porphyromonas gingivalis and Prevotella intermedia. Molecular Medicine Reports 22, 6 (2020). doi:10.3892/mmr.2020.11620
This study demonstrates dose-dependent antimicrobial activity of diosgenin against P. gingivalis and P. intermedia, including biofilm inhibition. The findings suggest diosgenin as a potential natural agent to prevent and treat periodontitis.

Conway de Macario, E., Macario, A. J. L. Methanogenic archaea in health and disease: A novel paradigm of microbial pathogenesis. Int. J. Med. Microbiol. 299, 85–97 (2009). doi:10.1016/j.ijmm.2008.06.011.
Methanogens in the oral cavity and gut contribute indirectly to disease by supporting pathogenic microbial communities, suggesting a new paradigm of microbial pathogenesis.

Corega, C., et al. The benefits of Quercetin for dentistry and maxillofacial surgery: A systematic review. Minerva Stomatologica 62 (2013)
Quercetin exhibits antioxidant, anti-inflammatory, and antimicrobial effects, showing preventive and therapeutic potential in oral diseases including periodontitis, oral lesions, and dental caries.

Corega, C., Vaida, L., Festila, D. G., et al. The benefits of Quercetin for dentistry and maxillofacial surgery: A systematic review. Minerva Stomatologica 62 (2013).
Quercetin, a polyphenolic flavonoid, demonstrates anti-inflammatory, antioxidant, and anti-cancer effects in oral medicine, showing preventive and therapeutic potential against dental caries, periodontal disease, and oral lesions.

Crump, K. E., Sahingur, S. E. Microbial Nucleic Acid Sensing in Oral and Systemic Diseases. Journal of Dental Research 95, 14–22 (2016). doi:10.1177/0022034515609062.
Intracellular pattern recognition receptors, including TLRs, detect microbial nucleic acids and propagate inflammatory responses, linking oral diseases such as periodontitis to systemic conditions like atherosclerosis, cancer, and autoimmune disorders.

Czesnikiewicz-Guzik, M., Bielanski, W., Guzik, T. J., Loster, B., & Konturek, S. J. Helicobacter pylori in the oral cavity and its implications in gastric infection, periodontal health, immunology and dyspepsia. J. Physiol. Pharmacol. 56, SUPPL. 6, 111–132 (2005).
Oral H. pylori alone does not significantly alter gastric hormone levels or act as a primary source for gastric infection, but may coexist with periodontal disease, highlighting complex host-microbe interactions.

Dai, L., Barrett, L., Plaisance-Bonstaff, K., Post, S. R., Qin, Z. Porphyromonas gingivalis coinfects with KSHV in oral cavities of HIV+ patients and induces viral lytic reactivation. Journal of Medical Virology 92, 2881–2891 (2020). doi:10.1002/jmv.26028.
This study demonstrates that P. gingivalis can promote lytic reactivation of Kaposi’s sarcoma-associated herpesvirus (KSHV) in HIV+ patients, revealing pathogen-virus interactions that may exacerbate oral oncogenesis in immunocompromised individuals.

Dai, L., Qiao, J., Yin, J., Goldstein, A., et al. Kaposi sarcoma-associated herpesvirus and Staphylococcus aureus coinfection in oral cavities of HIV-positive patients: A unique niche for oncogenic virus lytic reactivation. J. Infect. Dis. 221, 1458–1468 (2020). https://doi.org/10.1093/infdis/jiz249.
PAMPs from S. aureus and other oral bacteria promote KSHV lytic reactivation in HIV-positive patients, suggesting oral coinfections may facilitate virus-associated cancer.

Damek-Poprawa, M., Volgina, A., Korostoff, J., et al. Targeted inhibition of CD133+ cells in oral cancer cell lines. Journal of Dental Research 90, 2011. doi:10.1177/0022034510393511.
This study targeted cancer stem cells (CD133+) in oral squamous cell carcinoma using a toxin conjugated to anti-CD133 antibodies. Findings demonstrated selective inhibition of CD133+ cells without affecting healthy gingival epithelial cells, providing a potential therapeutic strategy for early-stage oral cancers influenced by periodontal pathogens.

Dan Sindelar. Virulent Porphyromonas gingivalis as the root cause of chronic inflammation—a chronic oral health perspective. Alzheimer’s Dement 19, S12 (2023). doi:10.1002/alz.079331.
Pg can modulate the oral microbiome and host immune response, promoting systemic inflammation and contributing to cardiovascular, autoimmune, neurodegenerative diseases, cancer, and metabolic disorders. Targeted early interventions in dental settings could reduce systemic disease burden.

De Carvalho Oliveira, G. R., Sant’Anna, C. D. C., Lamarão, L. M., et al. Quantitative difference of oral pathogen between individuals with gastric cancer and individuals without cancer. Oncotarget 12, 2021. doi:10.18632/ONCOTARGET.28034.
In this study, oral pathogen levels were quantitatively compared between gastric cancer patients and controls. Higher bacterial loads, including periodontal pathogens, were observed in cancer patients. While causality is not established, these findings suggest that oral hygiene and pathogen burden may influence digestive tract cancer risk.

Deng, Z.L., et al. Dysbiosis in chronic periodontitis: Key microbial players and interactions with the human host. Sci. Rep. 7, 995 (2017). https://doi.org/10.1038/s41598-017-03804-8.
Transcriptomic analysis shows red-complex pathogens upregulate virulence and metabolic functions in periodontitis, with potential systemic effects and links to cancer.

Di Spirito, F., Toti, P., Pilone, V., Carinci, F., Lauritano, D., & Sbordone, L. The association between periodontitis and human colorectal cancer: Genetic and pathogenic linkage. Life 10, 9 (2020); doi:10.3390/life10090211. Computer simulation analysis identifies 12 “leader genes” linking periodontitis to colorectal cancer, implicating dysregulated cell cycle control and immune-inflammatory pathways as mechanisms for oral-systemic carcinogenic interactions.

Dong, J., Li, W., Wang, Q., Chen, J., Zu, Y., Zhou, X., & Guo, Q. Relationships Between Oral Microecosystem and Respiratory Diseases. Front. Mol. Biosci. 8, 718222 (2022). https://doi.org/10.3389/fmolb.2021.718222.
Dysbiosis of the oral microecosystem, particularly via periodontal pathogens, contributes to respiratory diseases by acting as a reservoir for opportunistic pathogens and promoting inflammation, emphasizing oral health interventions as a preventive measure against pulmonary infections.

du Teil Espina, M., Fu, Y., van der Horst, D., Hirschfeld, C., López-Álvarez, M., Mulder, L. M., et al. Coating and Corruption of Human Neutrophils by Bacterial Outer Membrane Vesicles. Microbiol. Spectrum 10, e00753-22 (2022). https://doi.org/10.1128/spectrum.00753-22.
OMVs secreted by P. gingivalis coat neutrophils and degrade antimicrobial proteins while evading killing, creating a proinflammatory niche that favors bacterial survival and chronic periodontal inflammation.

Du, Q., Ma, X. Research progress of correlation between periodontal pathogens and systemic diseases. J. South. Med. Univ. 40, 24–31 (2020). doi:10.12122/j.issn.1673-4254.2020.05.24.
This review discusses how periodontal pathogens, including P. gingivalis, Tannerella forsythia, and Fusobacterium nucleatum, contribute to cardiovascular disease, diabetes, rheumatoid arthritis, and cancer through systemic inflammation.

Șurlin, P., Nicolae, F. M., Șurlin, V. M., et al. Could periodontal disease through periopathogen Fusobacterium nucleatum be an aggravating factor for gastric cancer? Journal of Clinical Medicine 9, 2020. doi:10.3390/jcm9123885.
This review highlighted the potential role of Fusobacterium nucleatum in linking periodontal disease and gastric cancer. Evidence suggests that chronic periodontal infection may exacerbate gastroenterological cancers, providing a rationale for future studies on oral-systemic disease connections.

Eady, E. A., Ingham, E. E. Propionibacterium acnes - friend or foe? Rev. Med. Microbiol. 5, 3 (1994). doi:10.1097/00013542-199407000-00003.
P. acnes exhibits both beneficial and pathogenic properties depending on host conditions. The bacterium can contribute to tissue destruction in dental and periodontal diseases, yet its immunomodulatory effects may have therapeutic potential in cancer, highlighting the complexity of commensal bacteria in oral health.

Elebyary, O., Barbour, A., Fine, N., Tenenbaum, H. C. & Glogauer, M. The crossroads of periodontitis and oral squamous cell carcinoma: immune implications and tumor promoting capacities. Front. Oral Health 1, 584705 (2020). https://doi.org/10.3389/froh.2020.584705

This review discusses how periodontitis (PD) can promote oral squamous cell carcinoma (OSCC) by creating an inflammatory microenvironment that favors cancer cell invasion, proliferation, and immune evasion. Altered immune and stromal responses in PD contribute to a tumor-promoting niche, highlighting potential targets for preventive and therapeutic strategies.

Emmadi, P., Krishna, P., Namasi, A., Nugala, B. Role of green tea as an antioxidant in periodontal disease: The Asian paradox. J. Indian Soc. Periodontol. 16, 131–135 (2012). doi:10.4103/0972-124X.100902.
Green tea catechins, including epigallocatechin gallate, can inhibit periodontal pathogens and reduce tissue destruction, suggesting a preventive role in oral inflammatory diseases.

F. Somma, R. Castagnola, D. Bollino, L. Marigo. Oral inflammatory process and general health. Part 1: The focal infection and the oral inflammatory lesion. Eur Rev Med Pharmacol Sci 14, 1065–1074 (2010).
Oral infections can act as focal points of systemic inflammation, influencing autoimmune responses, atherogenesis, and cancer development. Periodontal therapy reduces systemic inflammatory markers, illustrating oral-systemic disease connections.

Fan, X., Alekseyenko, A. V., Wu, J., et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based, nested case-control study. Cancer Research 76, 2016. doi:10.1158/1538-7445.am2016-4350.
This population-based study found that oral carriage of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans was associated with increased pancreatic cancer risk, while higher Fusobacteria abundance was linked to reduced risk. Results indicate that oral microbiota may play a direct role in pancreatic cancer etiology and highlight potential avenues for early prevention.

Fan, X., Alekseyenko, A. V., Wu, J., Peters, B. A., et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut 67, 120–127 (2018). doi:10.1136/gutjnl-2016-312580.
Nested case-control study revealed that oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were associated with higher pancreatic cancer risk, whereas Fusobacteria and Leptotrichia were linked to lower risk, supporting a role for oral microbiota in pancreatic oncogenesis.

Fan, Z., Tang, P., Li, C., et al. Fusobacterium nucleatum and its associated systemic diseases: epidemiologic studies and possible mechanisms. Journal of Oral Microbiology 15, 1 (2023). doi:10.1080/20002297.2022.2145729
This review summarizes how F. nucleatum contributes to systemic diseases—including cardiovascular disease, cancer, inflammatory bowel disease, and Alzheimer's—through immune modulation and inflammation, emphasizing its role beyond oral health.

Fernández-Rojas, B., Gutiérrez-Venegas, G. Flavonoids exert multiple periodontic benefits including anti-inflammatory, periodontal ligament-supporting, and alveolar bone-preserving effects. Life Sci. 209, 2018. doi:10.1016/j.lfs.2018.08.029.
The authors review flavonoids as multifunctional plant polyphenols with beneficial effects on periodontal tissues, including modulation of inflammatory responses, protection of periodontal ligament fibroblasts, and preservation of alveolar bone. Mechanistic evidence suggests flavonoids counteract pathogen-induced TLR-mediated inflammation, offering potential preventive and therapeutic applications.

Fitzsimonds, Z. R., Rodriguez-Hernandez, C. J., Bagaitkar, J., Lamont, R. J. From Beyond the Pale to the Pale Riders: The Emerging Association of Bacteria with Oral Cancer. Journal of Dental Research 99, 2020. doi:10.1177/0022034520907341.
This review described how periodontal pathogens like Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola contribute to oral squamous cell carcinoma through dysbiosis, proinflammatory signaling, and epithelial-to-mesenchymal transition. Functional interactions within microbial communities, rather than individual species, were highlighted as key drivers of oral cancer progression.

Fu, C., Brand, H. S., & Bikker, F. J. The applications of carbon dots in oral health: A scoping review. Oral Diseases 30, 4 (2024). doi:10.1111/odi.14702.
This scoping review summarizes 19 studies exploring carbon dots (CDs) in oral health, highlighting antimicrobial effects against oral pathogens, potential photodynamic therapeutic effects in oral cancer, and promotion of dental pulp and periodontal bone regeneration, emphasizing the broad applicability of CDs across oral health.

Fu, C., Brand, H. S., & Bikker, F. J. The applications of carbon dots in oral health: A scoping review. Oral Diseases 30, 4 (2024). doi:10.1111/odi.14702
This scoping review highlights the versatile potential of carbon dots (CDs) in oral health, including antimicrobial activity against oral pathogens, photodynamic killing of oral cancer cells, and promotion of dental pulp and periodontal bone regeneration. Among 152 articles screened, 19 studies were selected, illustrating CDs’ broad-spectrum applications beyond oral health.

Fu, Y., Haider Rubio, A., Gscheider, C. et al. Oral and dental infections: bacteria. In Encyclopedia of Infection and Immunity 3, 207 (2022). https://doi.org/10.1016/B978-0-12-818731-9.00207-X.
This chapter discusses major oral infections, including tooth decay, periodontal disease, and oral cancer, and emphasizes the role of P. gingivalis, F. nucleatum, and A. actinomycetemcomitans. It underscores the systemic impact of oral bacteria and the importance of a healthy oral microbiome.

Gallimidi, A. B., et al. Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Oncotarget 6, 26 (2015). doi:10.18632/oncotarget.4209
Using a murine model, chronic infection with P. gingivalis and F. nucleatum accelerated OSCC via IL-6/STAT3 signaling, demonstrating direct bacterial contribution to tumor progression.

Ganly, I., Yang, L., Giese, R.A., Hao, Y., Nossa, C.W., et al. Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus. Int. J. Cancer 145, 150–162 (2019). doi:10.1002/ijc.32152.
Enrichment of Fusobacterium, Prevotella, and Alloprevotella in OC-SCC patients lacking traditional risk factors highlights the independent role of periodontal pathogens in oral carcinogenesis.

Gao, S., Li, S., Ma, Z., Liang, S., Shan, T., Zhang, M., Zhu, X., Zhang, P., Liu, G., Zhou, F., Yuan, X., Jia, R., Potempa, J., Scott, D. A., Lamont, R. J., & Wang, H. Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer. Infectious Agents and Cancer 11, 1 (2016); doi:10.1186/s13027-016-0049-x. Detected P. gingivalis in 61% of esophageal squamous cell carcinoma tissues. Infection correlated with poor differentiation, metastasis, and reduced survival, suggesting the pathogen may serve as a biomarker and potential therapeutic target.

Gao, S.G., Yang, J.Q., Ma, Z.K., Yuan, X., Zhao, C., et al. Preoperative serum immunoglobulin G and A antibodies to Porphyromonas gingivalis are potential serum biomarkers for the diagnosis and prognosis of esophageal squamous cell carcinoma. BMC Cancer 18, 27 (2018). doi:10.1186/s12885-017-3905-1.
Elevated serum IgG and IgA against P. gingivalis were associated with early detection and poor prognosis in esophageal cancer, indicating the potential utility of these antibodies as biomarkers.

García-Arévalo, F., Leija-Montoya, A. G., González-Ramírez, J., et al. Modulation of myeloid-derived suppressor cell functions by oral inflammatory diseases and important oral pathogens. Frontiers in Immunology 15 (2024). doi:10.3389/fimmu.2024.1349067
This review highlights how oral pathogens, including P. gingivalis and F. nucleatum, modulate MDSC expansion, recruitment, and immunosuppressive activity. MDSC plasticity in response to oral inflammation may contribute to disease progression and could be a therapeutic target.

Geng, F., Liu, J., Guo, Y., Li, C., Wang, H., Wang, H., Zhao, H., Pan, Y. Persistent exposure to Porphyromonas gingivalis promotes proliferative and invasion capabilities, and tumorigenic properties of human immortalized oral epithelial cells. Frontiers in Cellular and Infection Microbiology 7, 57 (2017). doi:10.3389/fcimb.2017.00057.
Chronic P. gingivalis infection enhances proliferation, migration, and tumor-like transformation in oral epithelial cells, suggesting its role as a risk factor in oral squamous cell carcinoma and potential biomarker for disease monitoring.

Gholizadeh, P., Eslami, H., Yousefi, M., et al. Role of oral microbiome on oral cancers, a review. Biomedicine and Pharmacotherapy 84, 2016. doi:10.1016/j.biopha.2016.09.082.
This review highlights the role of oral microbiome in oral cancer development. Chronic periodontitis, particularly with Porphyromonas gingivalis and Fusobacterium nucleatum, creates a pro-inflammatory environment that may facilitate squamous cell carcinoma progression. The interplay between microbial communities and host inflammation is suggested as a key factor linking oral disease to carcinogenesis.

Gilliam, K. The critical role of the oral-systemic link in clinical practice. RDH 37, 4 (2017).
This article discusses the connection between periodontal disease and systemic conditions such as cardiovascular disease, diabetes, respiratory disease, hypertension, kidney disease, rheumatoid arthritis, pregnancy complications, and cancer. It emphasizes how oral inflammation, driven by periodontal pathogens, can trigger systemic immune responses, highlighting the importance of managing oral health to mitigate broader health risks.

Gölz, L., et al. Genome-wide transcriptome induced by Porphyromonas gingivalis LPS supports the notion of host-derived periodontal destruction and its association with systemic diseases. Innate Immunity 22, 1–15 (2016). https://doi.org/10.1177/1753425915616685.
LPS from P. gingivalis triggers broad monocyte transcriptional changes linked to immune dysregulation and systemic diseases, expanding insights into periodontal-systemic disease connections.

Groeger, S. E., Hudel, M., Zechel-Gran, S., Herrmann, J. M., Chakraborty, T., Domann, E., Meyle, J. Recombinant Porphyromonas gingivalis W83 FimA alters immune response and metabolic gene expression in oral squamous carcinoma cells. Clinical and Experimental Dental Research 8, 588–602 (2022). doi:10.1002/cre2.588.
Recombinant FimA protein from P. gingivalis W83 induces strong immunological and metabolic gene expression changes in oral carcinoma cells, highlighting its role in periodontitis pathogenesis and potential cancer-related effects.

Groeger, S., Domann, E., Gonzales, J. R., Chakraborty, T., & Meyle, J. B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by Porphyromonas gingivalis. Immunobiology 216, 1231–1241 (2011). https://doi.org/10.1016/j.imbio.2011.05.005.
P. gingivalis induces upregulation of B7-H1 and B7-DC receptors in oral squamous carcinoma cells and gingival keratinocytes, potentially facilitating immune evasion and linking periodontitis with enhanced tumor survival mechanisms.

Groeger, S., Herrmann, J. M., Chakraborty, T., Domann, E., Ruf, S., Meyle, J. Porphyromonas gingivalis W83 Membrane Components Induce Distinct Profiles of Metabolic Genes in Oral Squamous Carcinoma Cells. International Journal of Molecular Sciences 23, 3442 (2022). doi:10.3390/ijms23073442.
P. gingivalis W83 membranes trigger profound transcriptomic changes in oral squamous carcinoma cells, affecting immune response and metabolic pathways, illuminating molecular links between periodontal infection and oral cancer progression.

Gu, W. J., Lu, H. X., Zhang, Y., & Feng, X. P. Research progress on the study of the relationship between periodontitis and cancers of the digestive system. J. Prev. Treat. Stomatol. Dis. 29, 5 (2021). doi:10.12016/j.issn.2096-1456.2021.05.009.
Review of mechanisms linking periodontitis to esophageal, gastric, and colorectal cancers, highlighting microbial virulence factors, inflammation, immune modulation, and gene pathways, emphasizing oral health as a potential preventive target.

Guedes, R. A., et al. Association of SOCS1-820 (rs33977706) gene polymorphism with chronic periodontitis: A case-control study in Brazilians. Meta Gene 5 (2015). doi:10.1016/j.mgene.2015.06.005
Genetic variations in SOCS1 were linked to susceptibility to chronic periodontitis, highlighting the influence of host genetics in periodontal disease severity.

Hajishengallis, G. & Chavakis, T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat. Rev. Immunol. 21, 7 (2021). https://doi.org/10.1038/s41577-020-00488-6.
This review examines how periodontitis can exacerbate systemic inflammation and contribute to chronic diseases. It emphasizes mechanisms involving dissemination of pathogens, systemic inflammatory mediators, and bone marrow progenitor adaptation, suggesting novel therapeutic opportunities.

Hajishengallis, G. Interconnection of periodontal disease and comorbidities: evidence, mechanisms, and implications. Periodontol. 2000 89, 1 (2022). https://doi.org/10.1111/prd.12430.
This overview synthesizes evidence linking periodontitis with cardio-metabolic, cognitive, autoimmune, respiratory, and cancer-related comorbidities. Mechanistic insights from preclinical and interventional studies suggest causal relationships mediated by systemic inflammation, offering pathways for innovative therapeutic interventions.

Hakeem, K. R., Abdul, W. M., Hussain, M. M. & Razvi, S. S. I. Oral hygiene for healthy life. In SpringerBriefs in Public Health (Springer, 2019). https://doi.org/10.1007/978-3-030-04336-0_2.
This chapter stresses the central role of oral hygiene in preventing microbial invasion, dental decay, periodontal disease, and oral cancers. It highlights saliva’s enzymatic defense mechanisms and the broader implications of oral health on systemic well-being and longevity.

Hamada, M., Inaba, H., Nishiyama, K., Yoshida, S., et al. Transcriptomic analysis of Porphyromonas gingivalis-infected head and neck cancer cells: identification of PLAU as a candidate prognostic biomarker. J. Cell. Mol. Med. 28, 18167 (2024). doi:10.1111/jcmm.18167.
In vitro infection of HNSCC cells with P. gingivalis altered migration-related gene expression, highlighting PLAU as a prognostic biomarker linked to tumor size and lymph node metastasis.

Han, Y. W. Fusobacterium nucleatum: a commensal-turned pathogen. Curr. Opin. Microbiol. 23, 1–7 (2015). https://doi.org/10.1016/j.mib.2014.11.013.
This review highlights F. nucleatum’s dual role as an oral commensal and pathogen implicated in pregnancy complications, colorectal cancer, cardiovascular disease, rheumatoid arthritis, and respiratory infections. It details virulence mechanisms including adhesion, systemic dissemination, and host immune modulation, emphasizing its clinical significance.

Han, Y. W., Houcken, W., Loos, B. G., Schenkein, H. A., & Tezal, M. Periodontal disease, atherosclerosis, adverse pregnancy outcomes, and head-and-neck cancer. Adv. Dent. Res. 26, 1 (2014). doi:10.1177/0022034514528334.
This review emphasizes the systemic impact of periodontal infection, linking periodontitis with cardiovascular disease, pregnancy complications, and head-and-neck cancers, through mechanisms including endothelial dysfunction, molecular mimicry, and migration of oral pathogens like Fusobacterium nucleatum.

Harrandah, A., Chukkapalli, S. S., Dunn, W. J. R., Progulske-Fox, A., & Chan, E. K. Modulation of oral cancer cells survival and invasiveness by fusobacteria. Cancer Res. 79, 13 Suppl. (2019); doi:10.1158/1538-7445.am2019-2824. Demonstrates that F. nucleatum increases IL-8, TGF-β, MMP1/9, and oncogene expression (ZEB1, MYC, JAK1, STAT3), enhancing oral cancer cell invasiveness in vitro and in vivo.

Harrandah, A., Chukkapalli, S. S., Dunn, W. J. R., Progulske-Fox, A., & Chan, E. K. Modulation of oral cancer cells survival and invasiveness by fusobacteria. Proc. SABCS 2824 (2019). doi:10.1158/1538-7445.sabcs18-2824.
Experimental infection of oral cancer cells with periodontal pathogens (Tannerella forsythia, Treponema denticola, Porphyromonas gingivalis, Fusobacterium nucleatum) revealed enhanced invasiveness, IL-8 and TGF-β secretion, and upregulation of EMT and oncogenic markers. F. nucleatum alone sufficed to drive invasive phenotypes, confirmed in a murine oral tumorigenesis model.

Hayashi, M. et al. Intratumor Fusobacterium nucleatum promotes the progression of pancreatic cancer via the CXCL1-CXCR2 axis. Cancer Science 114, 9 (2023); doi:10.1111/cas.15901. Shows that F. nucleatum within pancreatic tumors enhances CXCL1-mediated autocrine/paracrine signaling, suppresses CD8+ T cells through MDSC recruitment, and accelerates tumor progression.

Helena Tlaskalová-Hogenová, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 93, 97–108 (2004). doi:10.1016/j.imlet.2004.02.005.
Commensal bacteria play a crucial role in mucosal immune development, but dysbiosis or pathogenic shifts may trigger chronic inflammation, autoimmunity, and systemic diseases, emphasizing the importance of host-microbiota homeostasis.

Henne, K., Schilling, H., Stoneking, M., Conrads, G., Horz, H. P. Sex-specific differences in the occurrence of Fusobacterium nucleatum subspecies and Fusobacterium periodonticum in the oral cavity. Oncotarget 9, 29 (2018). doi:10.18632/oncotarget.25042.
This study reports sex-specific prevalence of F. nucleatum subspecies in healthy individuals, with implications for systemic disease risk including colorectal cancer. Findings underscore the need for subspecies-level analysis in epidemiological studies of periodontal pathogens.

Hirschfeld, J., Higham, J., Blair, F., Richards, A. & Chapple, I. L. C. Systemic disease or periodontal disease? Distinguishing causes of gingival inflammation: a guide for dental practitioners. Part 2: cancer-related, infective, and other causes of gingival pathology. Br. Dent. J. 227, 1061–1071 (2019). doi:10.1038/s41415-019-1053-5.
Provides a clinical guide for distinguishing gingival inflammation caused by systemic disease, infection, or cancer from traditional plaque-induced periodontitis.

Huang, S., Yang, Z., Zou, D., Dong, D., Liu, A., Liu, W., & Huang, L. Rapid detection of nusG and fadA in Fusobacterium nucleatum by loop-mediated isothermal amplification. Journal of Medical Microbiology 65, 8 (2016). doi:10.1099/jmm.0.000300
This study developed a highly sensitive LAMP assay for rapid detection of F. nucleatum genes nusG and fadA. The method demonstrated 10-fold higher sensitivity than conventional PCR and high specificity, providing a practical tool for clinical diagnosis and detection of this pathogen’s virulence factor.

Ibieta-Zarco, B.R., de la Garza-Salazar, J.G., Ortiz-Hernández, J.F. Microbiota oral asociada a cáncer. J. Cancerol. 6, 1–11 (2019).
Metagenomic studies implicate oral microbiota, particularly P. gingivalis and F. nucleatum, in oral squamous cell carcinoma development via epithelial cell transformation and dysbiosis.

Idrissi Janati, A., Karp, I., Latulippe, J.-F., Charlebois, P., & Emami, E. Periodontal disease as a risk factor for sporadic colorectal cancer: results from COLDENT study. Cancer Causes and Control 33, 3 (2022); doi:10.1007/s10552-021-01541-y. This population-based case-control study found a 1.45-fold increased risk of colorectal cancer among individuals with a history of periodontal disease. Adjusted for multiple lifestyle and medical confounders, supporting the hypothesis that chronic oral inflammation may contribute to colorectal carcinogenesis.

Irani, S., Barati, I., & Badiei, M. Periodontitis and oral cancer—current concepts of the etiopathogenesis. Oncol. Rev. 14, 1 (2020); doi:10.4081/oncol.2020.465. Chronic periodontitis triggers inflammatory responses in gingival tissues that may predispose oral epithelium to malignant transformation, with risk factors including smoking, alcohol, and HPV.

Isah, A. D., Xue, X., Wang, X., & Dang, S. Commentary on the presence of periodontal pathogens in gastric cancer. Explor. Res. Hypothesis Med. 000 (2020); doi:10.14218/erhm.2020.00043. Identifies F. nucleatum, Parvimonas micra, and Peptostreptococcus stomatis as tumor-associated species in gastric and colorectal cancers, suggesting potential upstream periodontal reservoirs.

Isela, R. S.-N., Sergio, N.-C. & Juan J. M.-S. Ascorbic acid on oral microbial growth and biofilm. Pharma Innov. J. 2, 4 (2013).
This study demonstrates that ascorbic acid exhibits bactericidal activity against oral pathogens including S. mutans, P. gingivalis, and S. aureus. It inhibits biofilm formation and presents a potential natural therapeutic approach to prevent oral infections.

J. Lee, V. Taneja, R. Vassallo. Cigarette smoking and inflammation: Cellular and molecular mechanisms. J Dent Res 91, 142–149 (2012). doi:10.1177/0022034511421200.
Cigarette smoke induces chronic oral and systemic inflammation, impairing immunity and promoting periodontal disease and oral cancer via multiple molecular pathways, including Toll-like receptors, NF-κB, and MAPK signaling.

Jacob, V., Vellappally, S., Smejkalová, J. The influence of cigarette smoking on various aspects of periodontal health. Acta Med. Hradec Králové 50, 25–32 (2007). doi:10.14712/18059694.2017.52.
Smoking exacerbates periodontal disease by affecting immune response, promoting pathogen colonization, and impairing tissue healing, thereby increasing oral cancer risk.

Jain, P., Hassan, N., Khatoon, K., Mirza, M. A., Naseef, P. P., Kuruniyan, M. S., Iqbal, Z. Periodontitis and systemic disorder—an overview of relation and novel treatment modalities. Pharmaceutics 13, 81175 (2021). doi:10.3390/pharmaceutics13081175.
This review highlights mechanistic links between chronic periodontitis and systemic diseases such as cardiovascular disorders, diabetes, respiratory conditions, preterm birth, and cancer. It emphasizes the role of periodontal pathogens entering the bloodstream and discusses periodonto-therapeutic strategies for early intervention to prevent systemic complications.

Jan, M.-S., Chen, W.-T., Chen, Y.-J., et al. Probiotics ameliorate Porphyromonas gingivalis-promoted pancreatic cancer progression in oncogenic Kras transgenic mice. Cancer Research 77, 2017. doi:10.1158/1538-7445.AM2017-235.
In a murine model, oral administration of Lactobacillus reuteri and Lactobacillus paracasei mitigated Porphyromonas gingivalis-induced pancreatic cancer progression. Probiotics suppressed EMT marker expression and oncogenic signaling, highlighting the therapeutic potential of microbiota modulation in cancer prevention.

Jan, M.-S., Chen, W.-T., Chen, Y.-J., Lin, C.-W., Chang, W.-W., Tsai, C.-H., & Peng, J.-S. Probiotics ameliorate Porphyromonas gingivalis-promoted pancreatic cancer progression in oncogenic Kras transgenic mice. Cancer Research 77, 13 Suppl. 1 (2017); ISSN 1538-7445. Demonstrates in vivo that oral administration of probiotics (Lactobacillus reuteri and L. paracasei) reduces pancreatic cancer progression promoted by P. gingivalis, suppressing epithelial-mesenchymal transition (EMT) markers. Suggests that modulation of the microbiota can enhance anti-tumor immunity.

Jia, J., Zhou, Y., Wang, X., & Liu, Y. Subgingival microbiome dynamic alteration associated with necrotizing periodontal disease: A case report. Medicine 100, e24311 (2021). doi:10.1097/MD.0000000000024311
A case study of a 33-year-old female with necrotizing periodontal disease revealed early-stage microbial shifts, with enrichment of Neisseria, Corynebacterium, and Prevotella in lesions and Fusobacteria in unaffected sites. Local minocycline and systemic doxycycline led to rapid recovery. The study highlights subgingival microbial dynamics preceding clinical disease.

Jia, X., Liu, J., He, Y., Huang, X. Porphyromonas gingivalis secretion leads to dysplasia of normal esophageal epithelial cells via the Sonic hedgehog pathway. Front. Cell. Infect. Microbiol. 12 (2022). doi:10.3389/fcimb.2022.982636.
P. gingivalis culture media induces dysplastic changes in normal esophageal epithelium by activating the Sonic hedgehog pathway, enhancing proliferation and migration. The work supports mechanistic links between oral pathogens and esophageal carcinogenesis.

Jian, T.W., Mokhtar, N.M., Raja Ali, R.A., Wong, K.K. Manipulation of gut microbiota in in vitro model of colorectal cancer: positive effects of Lactobacillus rhamnosus against Fusobacterium nucleatum. IDDF2018-ABS-0149. (2018). doi:10.1136/gutjnl-2018-iddfabstracts.130.
In vitro assays using SW480 colorectal cancer cells demonstrated that the probiotic L. rhamnosus can outcompete the periodontal pathogen F. nucleatum, reducing pathogen-induced cell proliferation and highlighting its potential role in colorectal cancer prevention.

John A. Loudon. Preventing and correcting communicable and non-communicable chronic disease via amlexanox—dual 'no-nonsense' and inflammatory axis targeting. J Bioanal Biomed 5, 95–105 (2013). doi:10.4172/1948-593X.1000095.
Amlexanox, an immune-modulatory agent, may mitigate inflammation-driven diseases and pathogen-mediated effects, emphasizing its potential in managing chronic infectious and non-infectious conditions.

Kageyama, S., Nagao, Y., Ma, J., Asakawa, M., Yoshida, R., Takeshita, T., Hirosue, A., Yamashita, Y., & Nakayama, H. Compositional Shift of Oral Microbiota Following Surgical Resection of Tongue Cancer. Front. Cell. Infect. Microbiol. 10, 600884 (2020). doi:10.3389/fcimb.2020.600884.
This study analyzed the salivary microbiota of 25 tongue cancer patients before and after surgical resection. While total bacterial density remained unchanged, the composition shifted, with decreases in Streptococcus salivarius, Prevotella melaninogenica, and Prevotella histicola, and increases in dental plaque-associated bacteria such as Lautropia mirabilis, Neisseria flava, Streptococcus sanguinis, and Fusobacterium nucleatum. The findings underscore the need for careful postoperative oral care.

Kaiumov, K. A., Lyamin, A. V., Zhestkov, A. V., Bazhutova, I. V. Fusobacterium nucleatum: from a classic periodontal pathogen to a complete participant of carcinogenesis. Kliniceskaa Mikrobiologia i Antimikrobnaa Himioterapia 25, 13–18 (2023). doi:10.36488/cmac.2023.1.13-18.
This article reviews the transition of F. nucleatum from a periodontal pathogen to a contributor in colorectal and multiple other cancers, highlighting its mechanisms via adhesion proteins FadA and Fap2, inflammation, and β-catenin signaling.

Kamarajan, P., Ateia, I., Shin, J.M., Fenno, J.C., Kapila, Y.L. Treponema denticola, a periodontal pathogen, promotes stemness and migration in oral squamous cell carcinoma. Cancer Res. 76, 3294 (2016). doi:10.1158/1538-7445.am2016-3294.
T. denticola enhances stemness and migration in oral squamous carcinoma cells, potentially contributing to tumor progression, which can be mitigated by nisin treatment.

Kamarajan, P., Ateia, I., Shin, J.M., Fenno, J.C., Le, C., Zhan, L., Chang, A., Darveau, R., Kapila, Y.L. Periodontal pathogens promote cancer aggressivity via TLR/MyD88 triggered activation of Integrin/FAK signaling that is therapeutically reversible by a probiotic bacteriocin. PLoS Pathog. 16, e1008881 (2020). doi:10.1371/journal.ppat.1008881.
Key periodontal pathogens, including P. gingivalis, T. denticola, and F. nucleatum, enhanced oral squamous cell carcinoma aggressivity through TLR/MyD88-mediated integrin/FAK signaling, which could be inhibited by nisin, a probiotic bacteriocin.

Kapoor, S., Arora, P. & Wazir, S. S. Periodontal vaccines: need of an hour. Glob. Dent. (2018). https://doi.org/10.36879/gsl.dcr.2018.000118.
This article outlines the need for vaccines targeting key periodontal pathogens. Current treatments can only arrest disease progression, whereas vaccines could offer preventive strategies, reduce pathogen colonization, and serve as adjuncts to mechanical therapies, potentially mitigating systemic complications linked to periodontitis.

Kato, I., Vasquez, A. A., Moyerbrailean, G., et al. Oral microbiome and history of smoking and colorectal cancer. J. Epidemiol. Res. 2, 2 (2016); doi:10.5430/jer.v2n2p92. Analyzes oral rinse samples from 190 participants; smoking alters oral microbiome composition, and shifts in genera such as Lactobacillus and Rothia may influence colorectal cancer risk.

Kato, I., Zhang, J., & Sun, J. Bacterial-viral interactions in human orodigestive and female genital tract cancers. Cancers 14, 2 (2022); doi:10.3390/cancers14020425. Explores how interactions between viruses and bacteria can directly or indirectly influence carcinogenesis in head and neck, colon, gastric, liver, and cervical cancers. Highlights synergistic effects of microbial co-infection.

Kaur, J., Sanghavi, A., Chopra, A., Lobo, R., Saha, S. Antimicrobial and cytotoxicity properties of Plumeria alba flower extract against oral and periodontal pathogens: A comparative in vitro study. Journal of Indian Society of Periodontology 26, 329–337 (2022). doi:10.4103/jisp.jisp_329_21.
Plumeria alba flower extract exhibits broad antimicrobial activity against oral pathogens (P. gingivalis, A. actinomycetemcomitans, F. nucleatum, etc.) and shows low cytotoxicity against human gingival fibroblasts. This study suggests its potential as a natural alternative to chlorhexidine for periodontal therapy.

Kaviya, L., Roy, A., & Somasundaram, J. Novel trends in drug delivery and application of curcumin in dentistry. Indian J. Forensic Med. Toxicol. 14, 12400 (2020). doi:10.37506/ijfmt.v14i4.12400
Curcumin, a polyphenol from Curcuma longa, exhibits anti-inflammatory, antimicrobial, and anticancer properties relevant to dentistry. The review highlights challenges in oral bioavailability and the potential of advanced delivery systems—nanoparticles, liposomes, and cyclodextrin complexes—to enhance therapeutic efficacy in periodontal disease and oral cancer management.

Kazanowska-Dygdała, M., et al. The presence of Helicobacter pylori in oral cavities of patients with leukoplakia and lichen planus. Advances in Clinical and Experimental Medicine 29, 10 (2020). doi:10.17219/acem/124408
This study detects H. pylori in the oral cavity of patients with premalignant lesions, suggesting oral colonization may be a reservoir for gastric infection.

Kim, M. S., Shin, D. M., & Kim, M. S. Acidification induces OGR1/Ca2+/calpain signaling in gingival fibroblasts. Biochem. Biophys. Res. Commun. 496, 432–438 (2018). https://doi.org/10.1016/j.bbrc.2018.01.131.
Acidic oral environments impair gingival fibroblast function via OGR1/Ca²⁺-dependent calpain signaling, contributing to chronic tissue damage, impaired wound healing, and susceptibility to periodontal disease.

Kioi, M., Isono, H., Nakajima, S. Specific oral microbiome is closely associated with oral potentially malignant disorders and oral squamous cell carcinoma. Cancer Res. 83, 4238 (2023). doi:10.1158/1538-7445.am2023-4238.
Higher prevalence of P. gingivalis, T. denticola, and A. actinomycetemcomitans in OSCC and oral potentially malignant disorders suggests a critical role of oral dysbiosis in tumor development.

Kitamoto, S., et al. The Bacterial Connection between the Oral Cavity and the Gut Diseases. Journal of Dental Research 99, 9 (2020). doi:10.1177/0022034520924633
This review highlights oral-gut microbial interactions, showing how oral bacteria can translocate and potentially exacerbate gastrointestinal diseases, including colorectal cancer and IBD.

Kitamura, M., et al. Pathological characteristics of periodontal disease in patients with chronic kidney disease and kidney transplantation. Int. J. Mol. Sci. 20, 3413 (2019). https://doi.org/10.3390/ijms20143413.
Periodontal disease severity is higher in CKD and transplant patients due to immune suppression, contributing to systemic complications.

Knönen, E., Fteita, D., Gursoy, U. K., & Gursoy, M. Prevotella species as oral residents and infectious agents with potential impact on systemic conditions. Journal of Oral Microbiology 14, 1 (2022). doi:10.1080/20002297.2022.2079814.
The review updates knowledge on oral Prevotella species, emphasizing their role in dysbiotic biofilms, oral infections, systemic disease links, and potential involvement in head and neck cancers.

Koca-Ünsal, R. B., Chaurasia, A. Roles of exosomes in regenerative periodontology: a narrative review. Mol. Biol. Rep. 49, 9149–9161 (2022). doi:10.1007/s11033-022-08010-y.
Exosomes derived from mesenchymal stem cells show promise in periodontal regeneration and systemic disease diagnostics, highlighting their therapeutic potential.

Könönen, E., Fteita, D., Gursoy, U. K., & Gursoy, M. Prevotella species as oral residents and infectious agents with potential impact on systemic conditions. Journal of Oral Microbiology 14, 1 (2022). doi:10.1080/20002297.2022.2079814
This article details the role of oral Prevotella species in biofilms, periodontitis, and systemic disorders, including potential associations with head-and-neck cancers.

Kowalski, J., Górska, R., Cieślik, M. et al. What are the potential benefits of using bacteriophages in periodontal therapy? Antibiotics 11, 4 (2022). https://doi.org/10.3390/antibiotics11040446.
This review explores the potential of bacteriophages as targeted therapy for periodontitis. It emphasizes their ability to selectively eradicate pathogenic bacteria, reduce antibiotic use, and address antimicrobial resistance, providing an innovative approach to managing chronic periodontal infections.

Kwon, Y. D., Karbach, J., Wagner, W., Al-Nawas, B. Peri-implant parameters in head and neck reconstruction: Influence of extraoral skin or intraoral mucosa. Clinical Oral Implants Research 21, 257–264 (2010). doi:10.1111/j.1600-0501.2009.01763.x.
In head and neck cancer patients, colonization of implants by periodontal pathogens and yeasts correlates with peri-implant disease. The study suggests yeast and bacterial colonization as key predictors, with limited impact of irradiation or soft tissue origin.

Lafuente Ibáñez de Mendoza, I., et al. Role of Porphyromonas gingivalis in oral squamous cell carcinoma development: A systematic review. J. Periodontol. Res. 55, 1–12 (2020). https://doi.org/10.1111/jre.12691.
P. gingivalis contributes to OSCC via epithelial-mesenchymal transition, malignant cell proliferation, and invasion, highlighting periodontal disease control for cancer prevention.

Lam, G. A., et al. The Oral-Gut Axis: Periodontal Diseases and Gastrointestinal Disorders. Inflammatory Bowel Diseases 29, 7 (2023). doi:10.1093/ibd/izac241
This review examines how periodontal dysbiosis, involving P. gingivalis and F. nucleatum, affects gut microbial composition, potentially contributing to IBD and colorectal cancer.

Lamont, R.J., Fitzsimonds, Z.R., Wang, H., & Gao, S. Role of Porphyromonas gingivalis in oral and orodigestive squamous cell carcinoma. Periodontology 2000 89, 1–25 (2022). https://doi.org/10.1111/prd.12425.
P. gingivalis promotes oncogenesis through inflammation, apoptosis inhibition, epithelial-to-mesenchymal transition, and synergism with Fusobacterium nucleatum. Functional properties of the microbial community are more predictive of tumor development than composition alone.

Lan, Z., Zou, K. L., Cui, H., Zhao, Y. Y., & Yu, G. T. Porphyromonas gingivalis suppresses oral squamous cell carcinoma progression by inhibiting MUC1 expression and remodeling the tumor microenvironment. Mol. Oncol. 18, 1050–1066 (2024). https://doi.org/10.1002/1878-0261.13517.
High abundance of P. gingivalis in OSCC tumor microenvironments induces cell cycle arrest, downregulates MUC1 and CXCL17, and reverses immunosuppressive conditions, indicating context-dependent anti-tumor effects and potential therapeutic implications.

Leela Subhashini C Alluri, Andre Paes Batista da Silva, Shiv Verma, et al. Presence of specific periodontal pathogens in prostate gland diagnosed with chronic inflammation and adenocarcinoma. Cureus 13, e17742 (2021). doi:10.7759/cureus.17742.
Fusobacterium nucleatum was detected in prostate tissues with chronic inflammation, BPH, and adenocarcinoma, suggesting a potential microbial link between periodontal infection and prostatic disease progression.

Li, D. H., Li, Z. P., Zhang, Y., Zhou, G. Z., Ren, R. R., Zhao, H. J., et al. Fecal Fusobacterium nucleatum harbored virulence gene fadA are associated with ulcerative colitis and clinical outcomes. Microb. Pathog. 157, 104964 (2021). doi:10.1016/j.micpath.2021.104964
Fecal samples from 310 subjects revealed that UC patients had a higher prevalence of F. nucleatum and fadA gene positivity, particularly in severe cases with pancolitis. The findings implicate F. nucleatum strains harboring fadA in UC pathogenesis, linking oral-gut microbial translocation to disease severity.

Li, R., Xiao, L., Gong, T., et al. Role of oral microbiome in oral oncogenesis, tumor progression, and metastasis. Mol. Oral Microbiol. 38, e12403 (2023). doi:10.1111/omi.12403.
This review outlines the contributions of periodontal pathogens, including P. gingivalis, F. nucleatum, and T. denticola, in oral cancer initiation, progression, and metastasis, integrating microbial, viral, and fungal interactions.

Li, T. J., Hao, Y. H., Tang, Y. L., & Liang, X. H. Periodontal pathogens: a crucial link between periodontal diseases and oral cancer. Front. Microbiol. 13, 919633 (2022); doi:10.3389/fmicb.2022.919633. Details how pathogens directly interact with host epithelium and indirectly induce proinflammatory and carcinogenic microenvironments, reinforcing the importance of oral hygiene.

Li, Y., et al. Composition and function of oral microbiota between gingival squamous cell carcinoma and periodontitis. Oral Oncol. 107, 104710 (2020). https://doi.org/10.1016/j.oraloncology.2020.104710.
Periodontal pathogens including Fusobacterium, Peptostreptococcus, and Prevotella are enriched in GSCC tissues, while saliva contains more commensals, suggesting microbial influence on oral cancer progression.

Lin, I.-H. et al. Pilot study of oral microbiome and risk of pancreatic cancer. Cancer Research 73, 8 SUPPL. 1 (2013). Altered oral microbiota, including higher abundance of Bacteroides and lower levels of Corynebacterium and Aggregatibacter, may be associated with pancreatic cancer risk. This pilot study suggests that oral pathogens implicated in periodontitis could influence pancreatic carcinogenesis via systemic inflammatory pathways.

Liu, D., Liu, S., Liu, J., et al. sRNA23392 packaged by Porphyromonas gingivalis outer membrane vesicles promotes oral squamous cell carcinomas migration and invasion by targeting desmocollin-2. Mol. Oral Microbiol. 36, e12334 (2021). doi:10.1111/omi.12334.
sRNA23392 from P. gingivalis OMVs enhances OSCC cell invasion by targeting desmocollin-2, revealing a novel host-pathogen communication mechanism in tumor progression.

Liu, X. B., Gao, Z. Y., Sun, C. T., Wen, H., Gao, B., Li, S. B. & Tong, Q. The potential role of P. gingivalis in gastrointestinal cancer: A mini review. Infectious Agents and Cancer 14, 10.1186/s13027-019-0239-4 (2019). Porphyromonas gingivalis, a key periodontal pathogen, may promote gastrointestinal tumor development through chronic inflammation, immune modulation, and direct effects on epithelial cells, warranting further large-scale studies to clarify its oncogenic role.

Liu, X., Yang, L., Tan, X. PD-1/PD-L1 pathway: A double-edged sword in periodontitis. Biomed. Pharmacother. 159, 114215 (2023). doi:10.1016/j.biopha.2023.114215.
The PD-1/PD-L1 axis is upregulated by P. gingivalis, balancing periodontal inflammation and tissue protection while potentially enabling immune evasion, linking local periodontal and systemic diseases.

Loesche, W. J. Microbiology of dental decay and periodontal disease. In Medical Microbiology (1996).
This chapter reviews the microbial etiology of dental caries and periodontal disease, emphasizing the diversity of pathogenic species in dental plaque. It suggests that future therapies may focus on selective elimination or suppression of key pathogenic bacteria to maintain oral and systemic health.

Ma, Y., Yu, Y., Yin, Y., Wang, L., Yang, H., Luo, S., Zheng, Q., Pan, Y., & Zhang, D. Potential role of epithelial–mesenchymal transition induced by periodontal pathogens in oral cancer. J. Cell. Mol. Med. 28, 1 (2024). doi:10.1111/jcmm.18064.
This review highlights the role of periodontal pathogens in promoting epithelial–mesenchymal transition (EMT), increasing motility, aggressiveness, and stemness in oral cancer cells, suggesting EMT as a critical mechanism linking periodontitis to oral cancer progression.

Mahajan, B., Singh, V. Recent trends in probiotics and health management: a review. Int. J. Pharm. Sci. 5, 5 (2014).
Probiotics, defined as live beneficial microorganisms, modulate immune responses, inhibit pathogen colonization, and provide broad health benefits, including oral health. This review emphasizes their potential in preventing dental caries and periodontal diseases while underscoring the need for further clinical validation.

Mai, X., Genco, R. J., LaMonte, M. J., et al. Pathogenic oral bacteria and risk of incident cancer in postmenopausal women: The Buffalo OsteoPerio Study. Cancer Research 75, 2015. doi:10.1158/1538-7445.AM2015-848.
This cohort study investigated associations between periodontal pathogens and cancer risk among postmenopausal women. Presence of early-colonizing pathogens (Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus) showed borderline associations with total cancer and lung cancer risk. Findings emphasize the potential systemic impact of oral bacteria on carcinogenesis, although sample size limited statistical power.

Mai, X., Genco, R. J., LaMonte, M. J., Hovey, K. M., et al. Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study. J. Periodontol. 87, 3 (2016). doi:10.1902/jop.2015.150433.
Analysis of postmenopausal women found borderline associations between orange-complex pathogens (Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus) and total or lung cancer risk, while red-complex pathogens showed no clear association.

Malinowski, B. et al. The role of Tannerella forsythia and Porphyromonas gingivalis in pathogenesis of esophageal cancer. Infectious Agents and Cancer 14, 10.1186/s13027-019-0220-2 (2019). These red complex pathogens may contribute to esophageal cancer by inducing pro-inflammatory cytokines, impairing immune defenses, and upregulating matrix metalloproteinases and glucose transporters, highlighting the intersection of oral dysbiosis and tumorigenesis.

Martelli, M.L., et al. Periodontal disease and women’s health. Curr. Med. Res. Opin. 33, 1055–1066 (2017). https://doi.org/10.1080/03007995.2017.1297928.
Periodontitis is linked to female infertility, adverse pregnancy outcomes, osteoporosis, cardiovascular disease, autoimmunity, Alzheimer’s, and cancer, highlighting oral-systemic interactions in women’s health.

Mauceri, R., Coppini, M., Vacca, D., et al. Salivary Microbiota Composition in Patients with Oral Squamous Cell Carcinoma: A Systematic Review. Cancers 14, 21 (2022). doi:10.3390/cancers14215441.
Systematic review of 11 studies (687 OSCC patients, 648 controls) showed periodontal pathogens such as Fusobacterium and Prevotella were prevalent in OSCC patients, though a specific microbial signature for OSCC remains elusive.

McIlvanna, E., Linden, G. J., Craig, S. G., Lundy, F. T. & James, J. A. Fusobacterium nucleatum and oral cancer: a critical review. BMC Cancer 21, 10.1186/s12885-021-08903-4 (2021). Fusobacterium nucleatum, an oral periodontal pathogen, may contribute to oral carcinogenesis by promoting cell proliferation, invasion, chronic inflammation, and immune evasion. Biofilms on oral squamous cell carcinomas are enriched with anaerobic periodontal pathogens, supporting a potential mechanistic link between oral microbiota and tumor development.

Mdiaye, C. F. Oral health: a key to general health and well-being. Afr. Health Monit. 8, 5–15 (2008).
Oral health is critical for physical, psychological, and social well-being, influencing nutrition, communication, and disease susceptibility, particularly in underserved regions.

Mensch, K., et al. A szájüreg leggyakoribb bakteriális eredetű kórképeinek jellegzetességei, diagnosztikája és kezelése. Orv. Hetil. 160, 739–746 (2019). https://doi.org/10.1556/650.2019.31377.
Oral bacterial diseases, including caries and periodontitis, are linked to systemic conditions such as cardiovascular disease, diabetes, and respiratory infections; biofilm management is key.

Mensch, K., Nagy, G., Nagy, Á., Bródy, A. Characteristics, diagnosis and treatment of the most common bacterial diseases of the oral cavity. Orvosi Hetilap 160, 19 (2019). doi:10.1556/650.2019.31377.
The authors review common oral bacterial diseases, including caries and periodontitis, highlighting the systemic consequences of untreated infections such as cardiovascular disease, diabetes, and preterm birth. Oral microbiome management is emphasized for disease prevention.

Messeca, C., Balanger, M., Geoffroy, F. et al. Oral Kaposi sarcoma in two patients living with HIV despite sustained viral suppression: new clues. J. Clin. Exp. Dent. 14, 5 (2022). https://doi.org/10.4317/jced.59610.
This case report links oral Kaposi sarcoma with gingival inflammation in HIV-positive patients despite viral suppression, suggesting interactions between periodontal pathogens and oncogenic viruses. It highlights the need for careful oral monitoring in immunocompromised patients.

Michaud, D. S. Infections and pancreatic cancer. Gastrointestinal Diseases and Their Associated Infections 2019; doi:10.1016/B978-0-323-54843-4.00010-6. Pancreatic cancer is highly lethal, with over 70% mortality within a year. Observational studies suggest links between gastric ulcers, periodontal disease, and oral bacterial infections. Oral pathogens, particularly Porphyromonas gingivalis, may influence pancreatic carcinogenesis through systemic inflammation and immune modulation.

Michaud, D. S. Infections and pancreatic cancer. In Gastrointestinal Diseases and Their Associated Infections 10.1016/B978-0-323-54843-4.00010-6 (2019).

Michaud, D. S. Role of bacterial infections in pancreatic cancer. Carcinogenesis 34, 10.1093/carcin/bgt249 (2013). Periodontal pathogens such as Porphyromonas gingivalis may contribute to pancreatic carcinogenesis through systemic inflammation and dissemination to distant organs. This review highlights the interplay of bacteria, host immune response, and environmental factors in pancreatic cancer risk.

Michaud, D. S. Role of bacterial infections in pancreatic cancer. Carcinogenesis 34, 8 (2013); doi:10.1093/carcin/bgt249. Emphasizes mechanisms by which oral bacteria, especially P. gingivalis, may promote pancreatic cancer development, highlighting dissemination and chronic inflammatory effects.

Miller, D. P., Hutcherson, J. A., Wang, Y., et al. Genes contributing to Porphyromonas gingivalis fitness in abscess and epithelial cell colonization environments. Frontiers in Cellular and Infection Microbiology 7, AUG (2017). doi:10.3389/fcimb.2017.00378
Using Tn-Seq, the study identifies known and novel genes critical for P. gingivalis colonization of epithelial cells and survival in abscess models, advancing understanding of bacterial fitness and virulence mechanisms.

Miuna, S., Rostoka, D., Skadiņš, I. et al. The oral microbiome of smokeless tobacco users in Latvia. Proc. Latv. Acad. Sci., Sect. B 71, 1–2 (2017). https://doi.org/10.1515/prolas-2017-0006.
This study compares the oral microbiome of snus users with non-users, showing increased abundance and diversity of periodontal pathogens among tobacco users. The results suggest that smokeless tobacco may exacerbate periodontal disease risk and contribute to systemic health concerns.

Mohamed, P., Geetha, R., Lakshmi, T. Comparative Evaluation of Bacterial Population Among Smokers and Non-Smokers. J. Complement. Med. Res. 13, 5 (2022). doi:10.5455/jcmr.2022.13.05.08.
This study finds that smokers exhibit higher bacterial diversity, including pathogenic species such as Porphyromonas, which may contribute to periodontal disease. The work underscores the influence of smoking on oral microbial ecology and highlights the importance of public awareness of oral hygiene to mitigate periodontal risks.

Montemurro, N., Perrini, P., Marani, W., Chaurasia, B., Corsalini, M., Scarano, A., Rapone, B. Multiple brain abscesses of odontogenic origin. May oral microbiota affect their development? A review of the current literature. Applied Sciences (Switzerland) 11, 3316 (2021). doi:10.3390/app11083316.
This review highlights the contribution of oral microbiota to multiple brain abscesses (BAs) of odontogenic origin. Across 16 studies analyzed, pathogens originating from oral infections were implicated, emphasizing the need for multidisciplinary management and further research into microbiota-mediated systemic pathology.

Moshtaha, W. Oral complications of dental prosthetic for patients after chemotherapy and radiotherapy treatment. Dent. Hypotheses 12, 2 (2021). doi:10.4103/denthyp.denthyp_57_20
A case-control study in 92 cancer patients assessed changes in oral microflora following chemo/radiotherapy. No significant microbial shifts were observed in dental plaque over 7 days, and no correlation was found between oral mucositis and specific microorganisms, suggesting short-term therapy may not significantly alter microbial composition in denture wearers.

Muhangi, D., Gardiner, C. H., Ojok, L., Cranfield, M. R., Gilardi, K. V. K., Mudakikwa, A. B., & Lowenstine, L. J. Pathological lesions of the digestive tract in free-ranging mountain gorillas (Gorilla beringei beringei). Am. J. Primatol. 83, 1–14 (2021). doi:10.1002/ajp.23290
This study examined 60 deceased free-ranging mountain gorillas across Uganda, Rwanda, and DRC to identify gastrointestinal (GI) lesions. Enteritis, gastritis, and colitis were common, with most being subclinical. Gastritis was frequently chronic and linked to nematodiasis. Mortality directly attributable to GI lesions was low (8%), highlighting differences from captive populations. The findings improve understanding of GI pathology in endangered gorillas and inform conservation health strategies.

Mustilwar, R. G., Khan, N., Pasha, Z., Nelson, A., Bhople, T., Prasanna, P. S. & Deshmukh, K. S. Navigating the dental landscape: periodontal and microbiological considerations in head and neck cancer patients undergoing radiation therapy. Onkologia i Radioterapia 17, 10 (2023).
Review highlighting the impact of radiation therapy on oral health, including xerostomia, mucositis, and periodontitis, emphasizing microbial dysbiosis and interdisciplinary approaches to prevent periodontal complications in head and neck cancer patients.

Muwal, P., Kaur, N., & Kaur, G. Dual role of autophagy in periodontal disease. Int. J. Med. Sci. Diagn. Res. 5, 25–34 (2021). https://doi.org/10.32553/ijmsdr.v5i6.812.
Autophagy maintains cellular homeostasis and host defense against periodontal pathogens, with both protective and pathological roles in periodontitis.

Nagarajan, M., Gopinath, P., Ramasamy, S. Metagenomics: Implications in Oral Health and Disease. In Metagenomics: Perspectives, Methods, and Applications, 109–130 (2017). doi:10.1016/B978-0-08-102268-9.00009-4.
Oral metagenomics reveals complex microbial networks and dysbiosis associated with systemic diseases such as diabetes, cardiovascular disease, and colorectal cancer. The chapter highlights potential for microbiome-targeted diagnostics and therapeutics.

Nagasaki, A., Sakamoto, S., Arai, T., et al. Elimination of Porphyromonas gingivalis inhibits liver fibrosis and inflammation in NASH. Journal of Clinical Periodontology 48, 10 (2021). doi:10.1111/jcpe.13523
This study shows that clearing P. gingivalis odontogenic infection in a NASH mouse model significantly reduces liver inflammation and fibrosis markers, highlighting the systemic impact of periodontal pathogens on liver disease progression.

Narayanan, A., Söder, B., Meurman, J., Lundmark, A., Hu, Y. O. O., Neogi, U., & Yucel-Lindberg, T. Composition of subgingival microbiota associated with periodontitis and diagnosis of malignancy—a cross-sectional study. Front. Microbiol. 14, 1172340 (2023). doi:10.3389/fmicb.2023.1172340
A 10-year follow-up study analyzed subgingival microbiota in 50 periodontitis patients and 40 healthy controls, linking microbial profiles with cancer diagnoses. Periodontal pathogens like Treponema, Fretibacterium, and Prevotella were enriched in periodontitis. Distinct microbial signatures correlated with concurrent or later cancer development, suggesting oral microbiota as potential indicators of malignancy risk.

Negrut, R. L., Cote, A., & Maghiar, A. M. Exploring the Potential of Oral Microbiome Biomarkers for Colorectal Cancer Diagnosis and Prognosis: A Systematic Review. Microorganisms 11, 6 (2023). doi:10.3390/microorganisms11061586.
This systematic review suggests oral microbiome-derived biomarkers, particularly periodontopathogens like F. nucleatum, could serve as non-invasive diagnostic tools for colorectal cancer, pending further mechanistic studies.

Nguyen, H.D., Whitley-Williams, P.N., Uppaluri, L.P., Sangani, J., Simon, M.L., & Baig, A.S. Case report of atypical Lemierre's Syndrome associated with Fusobacterium nucleatum infection without internal or external jugular venous thrombophlebitis. Respiratory Medicine Case Reports 37, 101651 (2022). https://doi.org/10.1016/j.rmcr.2022.101651.
A 20-year-old female presented with necrotizing pneumonia, systemic osteomyelitis, and abscesses, linked to Fusobacterium nucleatum, highlighting a rare atypical presentation of Lemierre's Syndrome without internal jugular vein thrombophlebitis.

Nishikawa, M., Honda, M., Kimura, R., et al. Bacteriological examination of stomach mucosa and periodontal pocket in patients with gastric cancer: A study protocol. Annals of Cancer Research and Therapy 27, 2019. doi:10.4993/acrt.27.1.
This prospective study examined the link between periodontal disease and gastric cancer by analyzing bacterial cultures from periodontal pockets and stomach mucosa. Severity of periodontal disease correlated with the presence of bacteria in stomach tissue, suggesting that oral pathogens may translocate to the stomach and contribute to postoperative infectious complications in gastrointestinal surgery.

Nomura, Y., Inai, Y., Shimpo, Y., Okada, A., Yamamoto, Y., Sogabe, K., Wada, N., Hanada, N. Incidence of Postoperative Pneumonia and Oral Microbiome for Patients with Cancer Operation. Applied Sciences (Switzerland) 12, 2022. doi:10.3390/app12062920.
This study explored the relationship between oral microbiome composition and postoperative pneumonia in cancer patients. Using next-generation sequencing, Porphyromonas gingivalis, Fusobacterium nucleatum, Atopobium parvulum, and Enterococcus faecalis were identified as potential high-risk species. Poor oral hygiene and increased periodontal pathogens prior to surgery were associated with elevated pneumonia risk, highlighting the importance of preoperative oral care management.

Noronha, V.T., et al. Silver nanoparticles in dentistry. Dent. Mater. 33, 949–961 (2017). https://doi.org/10.1016/j.dental.2017.07.002.
Silver nanoparticles exhibit antimicrobial, anti-inflammatory, and antitumor properties; potential applications include dental materials, implants, and oral cancer therapies.

Núñez-Acurio, D., Bravo, D., & Aguayo, F. Epstein–Barr virus—oral bacterial link in the development of oral squamous cell carcinoma. Pathogens 9, 12 (2020). doi:10.3390/pathogens9121059.
This review discusses the oncogenic potential of P. gingivalis and Epstein–Barr virus (EBV) in oral squamous cell carcinoma, exploring mechanisms by which they independently or synergistically influence oral epithelial transformation.

Núñez-Acurio, D., Bravo, D., & Aguayo, F. Epstein–Barr virus—oral bacterial link in the development of oral squamous cell carcinoma. Pathogens 9, 12 (2020). doi:10.3390/pathogens9121059
This review proposes a synergistic model between P. gingivalis and Epstein–Barr virus in OSCC development, detailing mechanisms of chronic infection and oncogenic transformation in oral epithelial cells.

Nwizu, N. N., Marshall, J. R., Moysich, K., Genco, R. J., Hovey, K. M., et al. Periodontal disease and incident cancer risk among postmenopausal women: Results from the Women's Health Initiative Observational Cohort. Cancer Epidemiol. Biomark. Prev. 26, 8 (2017). doi:10.1158/1055-9965.EPI-17-0212.
In a cohort of 65,869 postmenopausal women, a history of periodontal disease was associated with increased total cancer risk (HR 1.14), including breast, lung, esophagus, gallbladder, and melanoma, indicating systemic oncogenic potential of periodontitis.

Nwizu, N., Wactawski-Wende, J., & Genco, R. J. Periodontal disease and cancer: Epidemiologic studies and possible mechanisms. Periodontol. 2000 83, 1 (2020); doi:10.1111/prd.12329. Reviews evidence linking periodontitis to systemic cancer risk, highlighting chronic inflammation and specific pathogens as potential mechanisms.

Ogawa, H., et al. Prevention of oral functional decline. Int. Dent. J. 72, 341–352 (2022). https://doi.org/10.1016/j.identj.2022.05.008.
Oral health maintenance in older adults prevents tooth loss, hyposalivation, and oral cancer; life-course interventions and risk factor reduction (tobacco, alcohol) are recommended.

Ogba, O., Olorode, O., Ogba, O. M., et al. Effect of tobacco smoking on oral microbial flora and the relationship with oral health in Calabar, Nigeria. International Journal of Biomedical Laboratory Science 6 (2017)
Tobacco smoking significantly altered oral microbial populations, favoring pathogenic species like S. aureus and K. pneumoniae. This microbial shift correlates with increased oral diseases, including periodontitis, emphasizing the health risks of smoking.

Öğrendik, M. Periodontal Pathogens in the Etiology of Pancreatic Cancer. Gastrointestinal Tumors 3, 10.1159/000452708 (2016). Red complex pathogens, including Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, may contribute to pancreatic cancer development by secreting peptidylarginine deiminase, potentially inducing p53 and K-ras mutations and promoting tumor progression.

Öğrendik, M. Periodontal pathogens in the etiology of pancreatic cancer. Gastrointestinal Tumors 3, 125–132 (2016); doi:10.1159/000452708. Red complex pathogens (P. gingivalis, Tannerella forsythia, Treponema denticola) may drive pancreatic oncogenesis via peptidylarginine deiminase, potentially inducing mutations in p53 and K-ras genes.

Ohtani, M. & Nishimura, T. The preventive and therapeutic application of garlic and other plant ingredients in the treatment of periodontal diseases (Review). Exp. Ther. Med. 18, 1–12 (2019). https://doi.org/10.3892/etm.2019.8382.
Herbal extracts and polyphenols, including aged garlic extract (AGE), exhibit anti-inflammatory, antimicrobial, and antioxidant activities; AGE specifically alleviates gingivitis symptoms, highlighting its promise as a therapeutic agent for periodontal disease, though additional clinical and mechanistic studies are needed.

Okuyama, K., Yanamoto, S. Oral bacterial contributions to gingival carcinogenesis and progression. Cancer Prev. Res. 16, 235–247 (2023). doi:10.1158/1940-6207.CAPR-22-0511.
Periodontitis-associated bacteria, including P. gingivalis, F. nucleatum, and P. intermedia, drive inflammation and upregulate pro-carcinogenic molecules in gingival squamous cell carcinoma.

Olsen I. From the Acta Prize Lecture 2014: the periodontal-systemic connection seen from a microbiological standpoint. Acta Odontol Scand 73, 585–591 (2015).
Periodontal bacteria can translocate beyond the oral cavity, triggering systemic inflammation and potentially contributing to cardiovascular disease, diabetes, adverse pregnancy outcomes, COPD, rheumatoid arthritis, and other systemic conditions. Current evidence mostly supports associations rather than causality, highlighting the need for long-term clinical studies.

Olsen, I., & Yilmaz, Ö. Possible role of Porphyromonas gingivalis in orodigestive cancers. J. Oral Microbiol. 11, 1 (2019). doi:10.1080/20002297.2018.1563410.
This review consolidates evidence for P. gingivalis as a keystone pathogen in chronic periodontitis with systemic tumorigenic effects, promoting EMT, immune dysregulation, metastasis, and chemoresistance in oral and gastrointestinal cancers.

Oral Cancer and Periodontal Disease

Oriuchi, M., Lee, S., Uno, K., Sudo, K., Kusano, K., Asano, N., et al. Porphyromonas gingivalis Lipopolysaccharide Damages Mucosal Barrier to Promote Gastritis-Associated Carcinogenesis. Dig. Dis. Sci. 69, 2150–2165 (2024). https://doi.org/10.1007/s10620-023-08142-6.
P. gingivalis LPS compromises gastric mucosal integrity, elevates ROS and TNFα, and activates TLR2-β-catenin signaling, promoting inflammation-associated gastric carcinogenesis.

Öztürk, A. Can Gastric Helicobacter pylori Eradication Increase by Eradication of Oral Helicobacter pylori by Periodontal Treatment? Literature Review. Curr. Res. Dent. Sci. 33, 123–132 (2023). https://doi.org/10.5152/CRDS.2023.4909.
Oral H. pylori serves as a hidden reservoir that reduces gastric eradication success; adjunctive periodontal therapy enhances eradication rates and supports integrated dental-gastroenterological interventions.

Pal, B., Bhuyan, S., Baishya, D., Das, B. Oral cancer stem cells modulate Fusobacterium nucleatum to acquire the capability to induce tumor stemness switch. Cancer Research 78, 2018. doi:10.1158/1538-7445.am2018-3064.
This study demonstrated that oral cancer stem cells can modulate Fusobacterium nucleatum, enhancing its ability to induce stemness in non-stem cancer cells. Findings suggest a bidirectional interaction between oral bacteria and tumor cells that may support cancer progression and stemness.

Pal, M., & Bearne, S. L. Inhibition of glutamate racemase by substrate-product analogues. Bioorganic and Medicinal Chemistry Letters 24, 5 (2014). doi:10.1016/j.bmcl.2013.12.114
Novel cyclic analogues partially inhibit Fusobacterium nucleatum glutamate racemase, suggesting potential leads for therapeutic development targeting periodontopathogens.

Park, D. G., Woo, B. H., Lee, B. J., et al. Serum levels of interleukin-6 and titers of antibodies against Porphyromonas gingivalis could be potential biomarkers for the diagnosis of oral squamous cell carcinoma. Int. J. Mol. Sci. 20, 2749 (2019). doi:10.3390/ijms20112749.
Elevated serum IL-6 and anti-P. gingivalis antibodies correlate with oral squamous cell carcinoma, highlighting their potential as diagnostic and prognostic biomarkers.

Paul D. Veith, Mikio Shoji, Nichollas E. Scott, Eric C. Reynolds. Characterization of the O-glycoproteome of Porphyromonas gingivalis. Microbiol Spectrum 10, e01502-21 (2022). doi:10.1128/spectrum.01502-21.
For the first time, O-linked glycosylation was confirmed in P. gingivalis, identifying 257 glycosylation sites across 145 proteins. Glycosylation primarily affects periplasmic proteins, influencing protein stability and function, with implications for pathogenicity and immune evasion.

Periodontal pathogens may influence pancreatic carcinogenesis through systemic inflammation and direct bacterial effects. Observational studies suggest links between periodontal disease, bacterial infections, and pancreatic cancer, while animal models provide mechanistic insights. Further research is needed to determine whether targeting specific pathogens could reduce disease progression.

Peters, B. A., Wu, J., Pei, Z., et al. Oral microbiome composition reflects prospective risk for esophageal cancers. Cancer Research 77, 2017. doi:10.1158/0008-5472.CAN-17-1296.
This prospective study found associations between specific periodontal pathogens, notably Tannerella forsythia and Porphyromonas gingivalis, and increased risk of esophageal adenocarcinoma and squamous cell carcinoma. Protective effects were noted for commensal species, suggesting microbial composition as a potential biomarker for esophageal cancer risk.

Peterson, D. E. et al. Microbiology of acute periodontal infection in myelosuppressed cancer patients. J. Clin. Oncol. 5, 9 (1987); doi:10.1200/JCO.1987.5.9.1461. Describes predominance of pathogens including Staphylococcus epidermidis, Candida albicans, S. aureus, and Pseudomonas aeruginosa in acute periodontal infections during granulocytopenia.

Petti, S., Scully, C. Polyphenols, oral health and disease: A review. Journal of Dentistry 37, 413–423 (2009). doi:10.1016/j.jdent.2009.02.003.
Dietary polyphenols concentrate in the oral cavity and exhibit preventive effects against periodontal disease, dental caries, and oral cancer through antimicrobial, antioxidant, and anti-inflammatory mechanisms, though further human studies are needed.

Pizzo, G., Guiglia, R., Campisi, G. Periodontal disease and systemic diseases: Interrelationships and interactions. In Periodontal Disease: Symptoms, Treatment and Prevention (Nova Science Publishers, 2011).
This chapter provides a comprehensive overview of the systemic consequences of periodontal disease, linking chronic periodontitis to cardiovascular disease, diabetes, adverse pregnancy outcomes, rheumatoid arthritis, osteoporosis, pancreatic cancer, and neurodegenerative disorders, emphasizing the emerging concept of “periodontal medicine.”

Pizzo, G., Guiglia, R., Lo Russo, L., & Campisi, G. Dentistry and internal medicine: From the focal infection theory to the periodontal medicine concept. Eur. J. Intern. Med. 21, 496–502 (2010). https://doi.org/10.1016/j.ejim.2010.07.011.
Chronic periodontitis may contribute to systemic diseases, including cardiovascular disease, diabetes, and cancer, supporting the evolution of periodontal medicine from classical focal infection theory.

Plaza, K., Kalinska, M., Bochenska, O., Meyer-Hoffert, U., Wu, Z., Fischer, J., et al. Gingipains of Porphyromonas gingivalis affect the stability and function of serine protease inhibitor of Kazal-type 6 (SPINK6), a tissue inhibitor of human kallikreins. J. Biol. Chem. 291, 18720–18733 (2016). https://doi.org/10.1074/jbc.M116.722942.
Gingipains secreted by P. gingivalis degrade SPINK6, compromising the regulation of kallikreins and providing a mechanistic link between periodontal infection and systemic tumorigenic or inflammatory processes.

Pushparathna, S. B., Somasundaram, J., Ganesh, S. B., et al. Awareness of use of implant coated with nanoparticles with antimicrobial properties. Int. J. Res. Pharm. Sci. 11, 2990–2997 (2020). doi:10.26452/ijrps.v11iSPL3.2990.
This study reviews the use of antimicrobial nanoparticles on dental implants, promoting enhanced biofilm resistance and oral health management.

Putri, D. A., Widodo, A. H. B., Ichsyani, M., Naufalin, R., & Oedjijono The activities of torch ginger flower (Etlingera elatior) ethanol extract on degradation of Porphyromonas gingivalis biofilm as periodontal pathogen. Journal of Indonesian Dental Association 6, 1 (2023). doi:10.32793/jida.v6i1.882
Ethanolic extract of torch ginger flower demonstrated dose-dependent degradation of P. gingivalis biofilms. At 25 mg/mL, its efficacy was comparable to chlorhexidine, suggesting potential as a natural adjuvant therapy for periodontitis without the adverse effects of long-term mouthwash use.

Qu, H., Zhang, W., Li, J., et al. A rapid and sensitive CRISPR-Cas12a for the detection of Fusobacterium nucleatum. Microbiol. Spectr. 12, 2 (2024). doi:10.1128/spectrum.03629-23.
The authors developed a CRISPR-Cas12a-based assay for rapid, sensitive, and low-cost detection of F. nucleatum, a periodontal pathogen implicated in oral and gastrointestinal diseases. This method enables large-scale screening with high specificity and potential clinical application.

Radaic, A., et al. Modulation of pathogenic oral biofilms towards health with nisin probiotic. Journal of Oral Microbiology 12, 1 (2020). doi:10.1080/20002297.2020.1809302
The nisin-producing probiotic Lactococcus lactis disrupts pathogenic oral biofilms and restores microbial diversity, suggesting therapeutic potential for maintaining oral health.

Radaic, A., Ye, C., Parks, B., et al. Modulation of pathogenic oral biofilms towards health with nisin probiotic. Journal of Oral Microbiology 12, 1 (2020). doi:10.1080/20002297.2020.1809302.
The nisin-producing probiotic Lactococcus lactis effectively prevents and disrupts pathogen-enriched oral biofilms, restoring microbial diversity and promoting healthier oral microbiomes.

Rajakaruna, A., Umeda, M., Uchida, K., et al. Possible translocation of periodontal pathogens into the lymph nodes draining the oral cavity. J. Microbiol. 50, 5 (2012). doi:10.1007/s12275-012-2030-8.
This study provides evidence that periodontal bacteria, including P. gingivalis and Tannerella forsythia, may translocate to lymph nodes via lymphatic drainage, independent of cancer status or patient gender, suggesting a mechanism for systemic dissemination of oral pathogens.

Ray, R. R. Dental biofilm: Risks, diagnostics and management. Biocatal. Agric. Biotechnol. 43, 102381 (2022). doi:10.1016/j.bcab.2022.102381.
Dental bio

Rekabi, A., Ram, A., Nazari, A., Arefnezhad, R., & Rezaei-Tazangi, F. Does crocin create new hope for the treatment of oral problems? A focus on periodontitis. Mol. Biol. Rep. 51, 1–13 (2024). https://doi.org/10.1007/s11033-024-09209-x.
Crocin, an active component of saffron, exerts anti-inflammatory and antioxidant effects while promoting collagen synthesis and osteoblast-osteoclast balance, suggesting its potential as a natural adjunct therapy for tissue repair in periodontitis.

Reynolds, M. A., Minah, G. E., Peterson, D. E., et al. Periodontal disease and oral microbial successions during myelosuppressive cancer chemotherapy. Journal of Clinical Periodontology 16, 1989. doi:10.1111/j.1600-051X.1989.tb01638.x.
This early study highlighted how periodontal disease can alter oral microbial communities during chemotherapy. Increases in Staphylococcus and yeast species were associated with prior periodontal disease, suggesting that oral health influences microbial shifts under immunocompromised conditions.

Rodriguez-Archilla, A., & Encina-Palazzolo, E. Presence of the Periodontal Bacterium Porphyromonas gingivalis in Patients With and Without Cancer: A Meta-analysis. Ann. Dent. 29, 3 (2022). doi:10.22452/adum.vol29no3.
Meta-analysis of 13 studies (1732 cancer patients, 3298 controls) demonstrated that P. gingivalis detection was 1.81 times more likely in cancer patients, with significant associations for colorectal and pancreatic cancers, reinforcing its potential role as a systemic oncogenic pathogen.

Sabine Groeger, Joerg Meyle. Oral mucosal epithelial cells. Front Immunol 10, 208 (2019). doi:10.3389/fimmu.2019.00208.
Oral epithelial cells act as a barrier against pathogens but can be manipulated by P. gingivalis and A. actinomycetemcomitans, which disrupt tight and adherens junctions and modulate cytokine production, supporting persistent inflammation and potentially promoting malignant transformation.

Sadighi Shamami, M., Sadighi Shamami, M., & Amini, S. Periodontal disease and tooth loss as risks for cancer: A systematic review. Iran. J. Cancer Prev. 4, 4 (2011). Systematic review suggests severe periodontitis and tooth loss are associated with increased risk of oral, esophageal, and gastrointestinal cancers after controlling for smoking and alcohol.

Sadighi Shamami, M., Sadighi Shamami, M., & Amini, S. Periodontal disease and tooth loss as risks for cancer: A systematic review of the literature. Iranian Journal of Cancer Prevention 4, 4 (2011); ISSN 2008-2398. This systematic review analyzed 17 epidemiologic studies and found consistent associations between periodontal disease or tooth loss and increased risk for oral, esophageal, gastric, and lung cancers. Even after adjusting for smoking and alcohol consumption, severe periodontal disease emerged as a potential risk factor for carcinogenesis, suggesting systemic inflammatory and microbial mechanisms.

Sahingur, S. E., & Yeudall, W. A. Chemokine function in periodontal disease and oral cavity cancer. Front. Immunol. 6, 214 (2015); doi:10.3389/fimmu.2015.00214. Describes how chemokines mediate host-microbiome interactions, chronic inflammation, and tumor progression in oral cavity cancers.

Sambashivaiah, S., Bilichodmath, S., Nanjaiah, N. & Kulal, R. Helicobacter pylori in periodontal pockets of chronic periodontitis patients with and without type II diabetes mellitus: a randomized controlled trial. Microbiol. Res. 2, 1 (2011). https://doi.org/10.4081/mr.2011.e12.
This study evaluates the prevalence of H. pylori in periodontal pockets among patients with chronic periodontitis, with or without type II diabetes. The findings indicate that meticulous periodontal therapy reduces H. pylori prevalence, supporting the role of dental interventions in controlling systemic infection risks.

Sanghavi, A. D., Chopra, A., Shah, A., et al. Evaluation of the antimicrobial, anti-adhesion, anti-biofilm and cell proliferation assay of a de-novo goji berry extract against periodontal pathogens: a comparative in-vitro study. bioRxiv (2022).
Goji berry extract exhibits antimicrobial, anti-biofilm, and anti-adhesion activity against P. gingivalis, comparable to chlorhexidine, offering a potential natural therapeutic for periodontal inflammation.

Sato, Y., Motoyama, S., Wakita, A., Kawakita, Y., et al. High TLR4 expression predicts a poor prognosis after esophagectomy for advanced thoracic esophageal squamous cell carcinoma. Esophagus 17, 4 (2020). doi:10.1007/s10388-020-00732-x.
The study correlates high expression of TLR4, a receptor for Gram-negative periodontal pathogens, with poor prognosis in esophageal squamous cell carcinoma patients. Combined high TLR4 and low TLR3 expression further worsened survival, highlighting the immunological link between oral pathogens and cancer progression.

Sedghi, L. M., Bacino, M., & Kapila, Y. L. Periodontal Disease: The Good, The Bad, and The Unknown. Front. Cell. Infect. Microbiol. 11, 766944 (2021). https://doi.org/10.3389/fcimb.2021.766944.
Periodontitis progression is driven by microbial dysbiosis, immune dysregulation, and systemic factors, highlighting the oral cavity’s role in systemic health and the potential of emerging therapeutic strategies.

Shhadeh, A., Dassa, L., Fahoum, J., Haj, N., Wiener, R., Mandelboim, O., Bachrach, G. Suppression of anti-tumor immunity by the Fusobacterium nucleatum protease fusolisin. Cancer Res. 83, 5893 (2023). doi:10.1158/1538-7445.am2023-5893.
F. nucleatum secretes fusolisin, a protease that cleaves NK cell activating receptors, inhibiting tumor cell killing and suggesting a mechanism by which oral pathogens promote immune evasion in cancer.

Shi, T., et al. Periodontopathogens Porphyromonas gingivalis and Fusobacterium nucleatum and Their Roles in the Progression of Respiratory Diseases. Pathogens 12, 9 (2023). doi:10.3390/pathogens12091110
This review connects periodontal pathogens to respiratory diseases, including COPD, pneumonia, and lung cancer, explaining mechanisms such as epithelial damage, inflammation, and pathogen synergy.

Shi, Y. T., He, J. M., Tong, Z. A., Qian, Y. J., Wang, Q. W., Jia, D. J. C., Zhu, W. J., Zhao, Y. X., Cai, B. B., Chen, S. J., & Si, M. S. Ligature-Induced Periodontitis Drives Colorectal Cancer: An Experimental Model in Mice. J. Dent. Res. 102, 6 (2023). doi:10.1177/00220345231158269.
Using murine models, ligature-induced periodontitis promoted colorectal cancer progression, associated with oral and gut microbial dysbiosis and suppressed anti-tumor immunity, particularly PD-1+ CD8+ T-cell infiltration, highlighting a microbiota-mediated link between periodontitis and colorectal carcinogenesis.

Shirin Arastu-Kapur, Mai Nguyen, Sean Broce, et al. PD-L1 is induced by the periodontal pathogen Porphyromonas gingivalis and can be blocked by small molecule gingipain inhibitors, including atuzaginstat. In: Proc J Immunother Cancer (2020). doi:10.1136/jitc-2020-sitc2020.0676.
In esophageal and other cancer cell lines, P. gingivalis induces PD-L1 via non-canonical Wnt pathway activation. Gingipain inhibitors, such as Kgp and Rgp blockers, prevent this immune evasion, suggesting therapeutic potential in combination with anti-PD-1 therapy.

Singh, S., Singh, S., Tiwari, M. B., Pal, U. S., & Kumar, S. Microflora analysis in postchemotherapy patients of oral cancer. Natl. J. Maxillofac. Surg. 10, 2 (2019); doi:10.4103/njms.NJMS_7_19. Pilot study shows persistence of periodontal pathogens such as F. nucleatum in dental plaque post-chemotherapy, with limited changes over 7 days.

Singh, V. P., Sharma, J., Babu, S., et al. Role of probiotics in health and disease: A review. J. Pak. Med. Assoc. 63, 253–257 (2013).
The review discusses probiotics’ mechanisms in modulating host immunity and oral microbiota, highlighting their preventive and therapeutic potential in oral and systemic diseases.

Slots, J. Life-threatening pathogens in severe/progressive periodontitis: Focal infection risk, future periodontal practice, role of the Periodontology 2000. Periodontol. 2000 84, 7–17 (2020). doi:10.1111/prd.12375.
Severe periodontitis is associated with systemic diseases, potentially mediated by herpesviruses and bacterial pathogens, emphasizing the importance of interdisciplinary preventive care.

Slots, J., Rams, T. E. New views on periodontal microbiota in special patient categories. J. Clin. Periodontol. 18, 402–410 (1991). doi:10.1111/j.1600-051X.1991.tb02309.x.
Periodontitis in immunocompromised or systemically diseased patients involves both classical and unusual periodontal pathogens, emphasizing the need for comprehensive microbial monitoring.

Slowey, P. D. & Nagelberg, R. H. The impact of salivary diagnostics. Dent. Econ. Oral Hyg. September issue (2016).
Salivary diagnostics offer a non-invasive, cost-effective, and patient-friendly method for early detection of diseases. This article emphasizes their use for identifying periodontal pathogens and explores ongoing research into salivary biomarkers for cancers and systemic conditions, demonstrating saliva’s potential as a diagnostic medium.

Sobocki, B. K. et al. Molecular mechanisms leading from periodontal disease to cancer. Int. J. Mol. Sci. 23, 2 (2022); doi:10.3390/ijms23020970. Highlights roles of P. gingivalis and F. nucleatum in tumorigenesis via RANKL-RANK signaling, circulating cytokines, and modulation of host immune responses.

Söder, B., et al. Periodontal microorganisms and diagnosis of malignancy: A cross-sectional study. Tumor Biology 43, 1 (2021). doi:10.3233/TUB-200066
This study investigates associations between specific periodontal bacteria (A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythia, T. denticola) and malignancy, showing statistical links but not causality.

Song, J. M., Woo, B. H., Lee, J. H., et al. Oral administration of Porphyromonas gingivalis, a major pathogen of chronic periodontitis, promotes resistance to paclitaxel in mouse xenografts of oral squamous cell carcinoma. Int. J. Mol. Sci. 20, 2494 (2019). doi:10.3390/ijms20102494.
Chronic exposure to P. gingivalis induced inflammation-mediated chemoresistance in oral cancer xenografts, modulated through serum IL-6, illustrating how periodontal pathogens influence cancer therapy outcomes.

Sun, J., Wang, F., Li, Y., et al. Chronic Periodontal Disease, Periodontal Pathogen Colonization, and Increased Risk of Precancerous Gastric Lesions. J. Periodontol. 88, 1225–1233 (2017). doi:10.1902/jop.2017.160829.
Higher colonization of T. denticola, T. forsythia, and A. actinomycetemcomitans is associated with decreased oral microbial diversity and an increased risk of precancerous gastric lesions, suggesting a potential role for oral pathogens in gastrointestinal carcinogenesis.

Sun, J., Yin, J., & Hou, B. The periodontal infection may be a contributing factor to the development of gastric cancer. Dent. Hypotheses 8, 1 (2017); doi:10.4103/2155-8213.202026. Proposes that chronic periodontal infections could increase gastric cancer risk via systemic inflammation and enhanced nitrosamine exposure.

Takasaki, A. A., Aoki, A., Mizutani, K., et al. Application of antimicrobial photodynamic therapy in periodontal and peri-implant diseases Bacterial elimination using conventional methods in periodontal therapy. Periodontology 2000 51 (2009).
Photodynamic therapy, combining photosensitizers and low-level light, effectively eliminates periodontal pathogens and is emerging as a promising noninvasive adjunct for periodontal and peri-implant disease management.

Takasaki, A. A., et al. Application of antimicrobial photodynamic therapy in periodontal and peri-implant diseases Bacterial elimination using conventional methods in periodontal therapy. Periodontology 2000 51 (2009)
Photodynamic therapy, combining a photosensitizer with low-level light energy, effectively eliminates periodontal pathogens. This review discusses preclinical and clinical evidence for its use in periodontal and peri-implant disease management.

Tan, Q., Ma, X., Yang, B. et al. Periodontitis pathogen Porphyromonas gingivalis promotes pancreatic tumorigenesis via neutrophil elastase from tumor-associated neutrophils. Gut Microbes 14, 1 (2022). https://doi.org/10.1080/19490976.2022.2073785.
This study demonstrates that P. gingivalis accelerates pancreatic tumor growth by promoting a neutrophil-dominated proinflammatory microenvironment. The findings highlight a mechanistic link between periodontitis and pancreatic cancer, revealing potential therapeutic targets.

Tan, Y. Q., Zhang, J., & Zhou, G. Autophagy and its implication in human oral diseases. Autophagy 13, 2 (2017). doi:10.1080/15548627.2016.1234563.
Autophagy modulates oral disease pathogenesis, influencing microbial clearance, inflammation, tumor progression, and resistance to therapy, with roles varying depending on disease context and progression.

Tan, Y. Q., Zhang, J., & Zhou, G. Autophagy and its implication in human oral diseases. Autophagy 13, 2 (2017). doi:10.1080/15548627.2016.1234563
This review discusses autophagy in oral diseases, highlighting its dual role in cytoprotection and disease progression. Dysregulated autophagy is implicated in oral cancer, periodontitis, and oral infections.

Tefiku, U., Popovska, M., Cana, A., Zendeli-Bedxeti, L., Recica, B., Spasovska-Gjorgovska, A., Spasovski, S. Determination of the Role of Fusobacterium nucleatum in the Pathogenesis in and Out the Mouth. Prilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki) 41, 1–15 (2020). doi:10.2478/prilozi-2020-0026.
Fusobacterium nucleatum, though a normal oral commensal, is a key Gram-negative pathogen in periodontal disease and systemic disorders. This review highlights its role in polymicrobial biofilm formation and pathogenic mechanisms in oral and systemic conditions, including gingivitis, periodontitis, coronary heart disease, colorectal cancer, and pregnancy complications.

Teshima, R., Hanada, K., Akada, J. et al. Aggregatibacter actinomycetemcomitans infection causes DNA double-strand breaks in host cells. Genes Cells 23, 4 (2018). https://doi.org/10.1111/gtc.12570.
This study shows that infection with A. actinomycetemcomitans induces DNA double-strand breaks in host cells independent of apoptosis. The findings suggest a potential mechanism linking periodontal pathogens to genomic instability and increased risk of oral carcinogenesis.

Tortora, S. C., Spagnardi, M., Paredes, J., et al. Markers of periodontitis in the setting of colon cancer in African American patients. Cancer Epidemiology, Biomarkers & Prevention 32, 2023. doi:10.1158/1538-7755.disp22-c011.
This pilot study evaluated periodontal pathogen Fusobacterium nucleatum and cytokine markers in African American colon cancer patients. Increased inflammatory markers and presence of Fn were noted, particularly in right-sided colon cancers, suggesting that periodontitis-associated bacteria may influence tumor location and progression.

Tsai, M.S., Chen, Y.Y., Chen, W.C., Chen, M.F. Streptococcus mutans promotes tumor progression in oral squamous cell carcinoma. J. Cancer 13, 3847–3860 (2022). doi:10.7150/jca.73310.
Abundance of S. mutans in oral biofilms correlates with aggressive oral squamous cell carcinoma, promoting epithelial-mesenchymal transition and IL-6-mediated tumor progression.

Uchiyama, K., & Yamada, M. An examination of the effect of New Disinfectant (MatatacoroTM) for Patients with terminal Oral Cancer or abscess. J. Oral Maxillofac. Surg. 72, 9 (2014). doi:10.1016/j.joms.2014.06.172.
The study demonstrated that a novel disinfectant, MatatacoroTM, effectively reduced oral malodor and inflammation in terminal oral cancer patients, including activity against P. gingivalis, Treponema denticola, Treponema forsythia, and Aggregatibacter actinomycetemcomitans, improving quality-adjusted life years.

Umezawa, K., Hayashi, S., Tsuzukibashi, O. et al. One step multiplex PCR for identifications at subspecies level of Fusobacterium nucleatum and Fusobacterium necrophorum. Open J. Stomatol. 12, 6 (2022). https://doi.org/10.4236/ojst.2022.126018.
This study presents a one-step multiplex PCR method that accurately distinguishes subspecies of F. nucleatum and F. necrophorum without DNA extraction. The technique enhances diagnostic precision and efficiency for clinically important Fusobacterium species.

Valverde, A., Seal, A., Nares, S., Shukla, D., & Naqvi, A. R. Human herpesvirus-encoded MicroRNA in host-pathogen interaction. Adv. Biol. Regul. 82, 100829 (2021). https://doi.org/10.1016/j.jbior.2021.100829.
HHV-encoded microRNAs modulate host transcriptomes, immune responses, and viral latency, influencing oral disease progression and systemic pathologies, suggesting potential for diagnostic and therapeutic applications.

Van Zuylen, E. M., Ferguson, S. A., Hughes, A., Rennison, D., Brimble, M. A., & Cook, G. M. Disruption of metallostasis in the anaerobic human pathogen Fusobacterium nucleatum by the zinc ionophore PBT2. ACS Infect. Dis. 7, 1894–1907 (2021). doi:10.1021/acsinfecdis.0c00887
The zinc ionophore PBT2 potently inhibited F. nucleatum growth in planktonic and biofilm states. Mechanistic analyses revealed perturbations in intracellular Zn and Fe homeostasis, highlighting metallostasis disruption as a promising targeted antimicrobial strategy against anaerobic pathogens without broadly impacting commensal flora.

Vasquez, A. A., Ram, J. L., Qazazi, M. S., Sun, J., & Kato, I. Oral Microbiome: Potential Link to Systemic Diseases and Oral Cancer. In Mechanisms Underlying Host-Microbiome Interactions in Pathophysiology of Human Diseases (2018); doi:10.1007/978-1-4939-7534-1_9. Reviews the human oral microbiome, highlighting that beyond local periodontal disease, oral bacteria—including opportunistic pathogens—may contribute to systemic diseases such as cardiovascular disease, chronic kidney disease, Alzheimer's, rheumatoid arthritis, and oral cancers. Mechanistic evidence points to bacterial virulence factors that facilitate immune evasion, inflammation, and cytotoxicity.

Villalobos, V., Garrido, M., Reyes, A., Fernández, C., Diaz, C., Torres, V. A., González, P. A., & Cáceres, M. Aging envisage imbalance of the periodontium: A keystone in oral disease and systemic health. Front. Immunol. 13, 1044334 (2022). https://doi.org/10.3389/fimmu.2022.1044334.
Aging impairs gingival fibroblast function, collagen synthesis, and immune cell activity, while altering macrophage phenotypes and salivary antimicrobial peptides, facilitating periodontitis and its systemic connections, including neurodegenerative and cancerous conditions.

Vogtmann, E., Hua, X., Yu, G., et al. The human oral microbiota and risk of lung cancer: An analysis of three prospective cohort studies. Cancer Research 80, 2020. doi:10.1158/1538-7445.mvc2020-a39.
Analyzing oral microbiota from prediagnostic samples, the study found higher alpha diversity associated with reduced lung cancer risk, particularly for squamous cell carcinoma and former smokers. These results suggest that oral microbial composition years before diagnosis may impact lung cancer susceptibility.

Vozza, I., Caldarazzo, V. & Ottolenghi, L. Changes in microflora in dental plaque from cancer patients undergoing chemotherapy and the relationship of these changes with mucositis: a pilot study. Med. Oral Patol. Oral Cir. Bucal 20, e199–e207 (2015). doi:10.4317/medoral.19934.
Pilot study examining dental plaque microflora in 30 cancer patients receiving chemotherapy found no significant changes in microbial composition or correlations with oral mucositis within 7 days.

Wang, B., Deng, J., Donati, V., Merali, N., Frampton, A. E., Giovannetti, E., & Deng, D. The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review. Pathogens 13, 1 (2024). doi:10.3390/pathogens13010093.
This review examines how keystone pathogens P. gingivalis and F. nucleatum contribute to oral squamous cell carcinoma (OSCC), colorectal cancer, and pancreatic ductal adenocarcinoma, highlighting epidemiological correlations and proposing hypotheses for their synergistic pathogenic effects.

Wang, B., Deng, J., Donati, V., Merali, N., Frampton, A. E., Giovannetti, E., & Deng, D. The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review. Pathogens 13, 1 (2024). doi:10.3390/pathogens13010093
This narrative review explores the interplay of keystone periodontal pathogens P. gingivalis and F. nucleatum in oral and gastrointestinal cancers, emphasizing their prevalence in OSCC, CRC, and PDAC. The authors propose mechanistic hypotheses for pathogen interactions that could influence tumor progression.

Wang, C., Hong, L., Zhang, Z., Wang, Y. Research progress on the relationship between Porphyromonas gingivalis and the malignancy of the digestive system and possible pathogenetic mechanism. Hua Xi Kou Qiang Yi Xue Za Zhi 37, 545–552 (2019). doi:10.7518/hxkq.2019.05.013.
P. gingivalis, a keystone periodontal pathogen, is increasingly recognized for its role in gastrointestinal cancers, with mechanisms including systemic inflammation and microbial invasion beyond the oral cavity.

Wang, X., Jia, Y., Wen, L., Mu, W., Wu, X., Liu, T., et al. Porphyromonas gingivalis promotes colorectal carcinoma by activating the hematopoietic NLRP3 inflammasome. Cancer Res. 81, 2651–2665 (2021). doi:10.1158/0008-5472.CAN-20-3827.
P. gingivalis colonization promotes colorectal tumorigenesis by recruiting myeloid cells and inducing a proinflammatory microenvironment via NLRP3 inflammasome activation, linking oral pathogens to distal digestive cancers.

Wu, W., Wu, Y. & Zhao, L. Research progress on the relationship between Porphyromonas gingivalis and oral squamous cell carcinoma. West China J. Stomatol. 33, 6 (2015).
This review consolidates evidence connecting chronic periodontitis with head and neck cancers, particularly oral squamous cell carcinoma (OSCC). It highlights how P. gingivalis may influence OSCC progression through chronic inflammation, immune modulation, and potential molecular pathways, emphasizing the pathogen’s broader oncogenic potential.

Wu, Z., Han, Y., Wan, Y., et al. Oral microbiome and risk of incident head and neck cancer: A nested case-control study. Oral Oncol. 137, 106305 (2023). doi:10.1016/j.oraloncology.2022.106305.
Nested case-control analysis showed higher oral microbial diversity and presence of red- and orange-complex periodontal pathogens were associated with reduced head and neck cancer risk, suggesting that overall oral microbiome composition and fungi may modulate cancer susceptibility.

Wu, Z., Han, Y., Wan, Y., et al. The oral microbiome and the risk of head and neck cancer: A nested case-control study in the NIH-AARP. Cancer Research 82, 2022. doi:10.1158/1538-7445.am2022-687.
Using prediagnostic oral wash samples, this study observed that higher alpha-diversity and relative abundance of red- and orange-complex periodontal pathogens were associated with reduced head and neck cancer risk. The presence of oral fungi similarly correlated with lower risk, suggesting a complex protective role of oral microbial diversity.

Xian, W., Ren, B., & Cheng, L. Research progress on the relationship between periodontal pathogens and colorectal cancer. J. Prev. Treat. Stomatol. Dis. 31, 7 (2023); doi:10.12016/j.issn.2096-1456.2023.07.009. Describes how F. nucleatum and P. gingivalis affect colorectal cancer cell proliferation, apoptosis inhibition, immune escape, metastasis, and promotion of a pro-inflammatory tumor microenvironment.

Xiao, L., Zhang, Q., Peng, Y., et al. The effect of periodontal bacteria infection on incidence and prognosis of cancer: A systematic review and meta-analysis. Med. 99, 15 (2020). doi:10.1097/MD.0000000000019698.
Meta-analysis of 39 studies (7184 participants) showed that infection with P. gingivalis and Prevotella intermedia increased cancer incidence and predicted poorer prognosis, while other periodontal pathogens (T. forsythia, T. denticola, A. actinomycetemcomitans, F. nucleatum) showed less consistent associations.

Yamada, C., Ho, A., Nusbaum, A., Xu, R., Davey, M. E., Nichols, F., Mao, C., Movila, A. Inhibitory effect of Porphyromonas gingivalis-derived phosphoethanolamine dihydroceramide on acid ceramidase expression in oral squamous cells. J. Cell. Mol. Med. 27, 9 (2023). doi:10.1111/jcmm.17722.
This study demonstrates that the P. gingivalis-derived lipid PEDHC suppresses acid ceramidase (ASAH1) expression in oral squamous carcinoma cells (OECM-1), promoting intracellular ceramide accumulation and inhibiting cell survival and migration. The findings highlight PEDHC as a potential therapeutic agent targeting OSCC and suggest further in vivo studies are warranted to explore its molecular mechanisms.

Yamamoto, Y., Kamiya, T., Yano, M., Huyen, V. T., et al. Oral microbial profile analysis in patients with oral and pharyngeal cancer reveals that tumoral Fusobacterium nucleatum promotes oral cancer progression by activating YAP. Microorganisms 11, 2957 (2023). doi:10.3390/microorganisms11122957.
Bioinformatics and in vivo studies identified F. nucleatum, particularly Fn. polymorphum, as a promoter of oral squamous cell carcinoma progression via YAP activation, highlighting a microbial target for oral cancer prevention.

Yoshida, A. & Ikegami, A. Genetic transformation of Fusobacterium nucleatum. In Methods in Molecular Biology, 2210, 1–15 (Springer, 2021). https://doi.org/10.1007/978-1-0716-0939-2_5.
This chapter presents detailed protocols for the transformation of F. nucleatum strain 12230 using sonoporation and describes genetic complementation of knockout mutants. These methods enable functional studies of this periodontal pathogen, which has been linked to colorectal cancer and preterm birth, addressing the previous limitations in genetic manipulation of this bacterium.

Yu, X., Zhang, Y. Z., Yu, E. D., et al. Changes in gut microbiota of patients with colorectal adenoma and polyps: a case control study. Fudan Univ. J. Med. Sci. 45, 5 (2018). doi:10.3969/j.issn.1672-8467.2018.05.009.
The study identifies enrichment of oral pathogens, such as Porphyromonas spp., in the gut microbiota of colorectal adenoma patients, suggesting that oral microbial dysbiosis may contribute to early colorectal tumorigenesis.

Yu, Y., Yu, M.R., Kim, D.J., Kim, Y.H., Park, H.R. Analysis on exosomal small RNA derived from periodontal pathogen-infected Ca9-22 oral cancer cells. Korean J. Oral Maxillofac. Pathol. 46, 1–10 (2022). doi:10.17779/kaomp.2022.46.5.002.
Exosomal small RNAs from P. gingivalis-infected oral cancer cells may mediate communication in the tumor microenvironment, contributing to pathogen-driven tumor progression.

Yufei Yao, Xin Shen, Maolin Zhou, Boyu Tang. Periodontal pathogens promote oral squamous cell carcinoma by regulating ATR and NLRP3 inflammasome. Front Oncol 11, 722797 (2021). doi:10.3389/fonc.2021.722797.
Periodontitis-associated bacteria, specifically Porphyromonas gingivalis and Fusobacterium nucleatum, enhance OSCC cell proliferation and tumor growth in vitro and in vivo. These bacteria increase inflammatory cytokines, modulate immune cell populations, and dysregulate DNA damage response signaling via ATR-CHK1, suggesting a molecular link between periodontitis and OSCC progression.

Yusuf, K., Sampath, V., & Umar, S. Bacterial Infections and Cancer: Exploring This Association And Its Implications for Cancer Patients. International Journal of Molecular Sciences 24, 4 (2023); doi:10.3390/ijms24043110. Comprehensively reviews the role of bacterial infections in cancer. Highlights P. gingivalis and Fusobacterium nucleatum in periodontal disease, Helicobacter pylori in gastric cancer, and other species in gastrointestinal, cervical, and lung cancers. Discusses how persistent infections, immune evasion, and chronic inflammation contribute to tumorigenesis, and outlines implications for antibiotic use and microbe-based therapeutics.

Yvonne L. Kapila. Oral health’s inextricable connection to systemic health: Special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions. Periodontol 2000 87, 39–78 (2021). doi:10.1111/prd.12398.
Periodontal disease is linked to systemic conditions through genetic, environmental, microbial, and immune-mediated mechanisms. Viral and bacterial dysbiosis in subgingival plaque can exacerbate systemic inflammation, with implications for metabolic, cardiovascular, neurodegenerative, and reproductive health.

Zhang, D., Hou, J., Wu, Y., et al. Distinct gene expression characteristics in epithelial cell-Porphyromonas gingivalis interactions by integrating transcriptome analyses. International Journal of Medical Sciences 16, 10 (2019). doi:10.7150/ijms.33728
Meta-analysis of epithelial cell gene expression following P. gingivalis infection revealed upregulation of pathways promoting cell survival, proliferation, and angiogenesis, linking chronic infection to periodontitis progression and potentially oral cancer.

Zhang, J. C. Consideration for impacts of periodontitis on systemic health. Chin. J. Stomatol. 56, 6 (2021). https://doi.org/10.3760/cma.j.cn112144-20210314-00117.
The article examines how periodontitis contributes to systemic inflammation through bacteremia and release of pro-inflammatory mediators. It highlights links to cardiovascular disease, diabetes, and other chronic conditions, emphasizing the role of periodontal pathogens in driving systemic health risks.

Zhang, K. K., Sun, Y. & Pan, Y. H. Developments in research on the relationship between Porphyromonas gingivalis and non-oral diseases. J. Sichuan Univ. Med. Sci. 54, 1 (2023). https://doi.org/10.12182/20230160509.
This review discusses how P. gingivalis, beyond its role in periodontal disease, is associated with multiple systemic conditions including inflammatory bowel disease, cardiovascular disease, diabetes, Alzheimer’s disease, and cancer. It evaluates mechanisms of systemic dissemination and highlights its potential as a diagnostic biomarker or therapeutic target.

Zhang, K., He, C., Qiu, Y., Li, X., Hu, J. & Fu, B. Association of oral microbiota and periodontal disease with lung cancer: a systematic review and meta-analysis. J. Evid.-Based Dent. Pract. 23, 101897 (2023). doi:10.1016/j.jebdp.2023.101897.
This systematic review analyzed 28 studies on oral microbiota in lung cancer patients, showing lower alpha diversity associated with increased lung cancer risk. While most periodontal pathogens were not linked to lung cancer, Fusobacterium nucleatum emerged as a potential biomarker. Periodontal disease risk was largely confounded by smoking.

Zhang, Z., Wen, S., Liu, J., et al. Advances in the relationship between periodontopathogens and respiratory diseases (Review). Mol. Med. Rep. 29, 13166 (2024). doi:10.3892/mmr.2024.13166.
This review summarizes the mechanistic links between periodontal pathogens and pulmonary diseases including pneumonia, COPD, asthma, COVID-19, and lung cancer, emphasizing pathogen-mediated inflammation and respiratory epithelial dysregulation.

Zhou, B., Lu, J., Beck, J. D., Moss, K. L., Prizment, A. E., Demmer, R. T., Porosnicu Rodriguez, K. A., Joshu, C. E., Michaud, D. S., & Platz, E. A. Periodontal and other oral bacteria and risk of lung cancer in the Atherosclerosis Risk in Communities (ARIC) Study. Cancer Epidemiology Biomarkers & Prevention 32, 4 (2023); doi:10.1158/1055-9965.EPI-22-0601. Prospective study shows antibodies to orange complex bacteria (Campylobacter rectus, F. nucleatum, P. intermedia, Parvimonas micra, P. nigrescens) are associated with increased lung cancer risk, particularly in men. Highlights potential role of moderately pathogenic periodontal bacteria in lung carcinogenesis.

Zhou, J., Liu, L., Wu, P., & Zhao, L. Identification and characterization of non-coding RNA networks in infected macrophages revealing the pathogenesis of Fusobacterium nucleatum-associated diseases. BMC Genomics 23, 1–18 (2022). doi:10.1186/s12864-022-09052-z
Transcriptomic analysis of macrophages infected with F. nucleatum identified dysregulated mRNAs, miRNAs, lncRNAs, and circRNAs, revealing ceRNA networks controlling immune pathways such as MAPK, Toll-like receptor, and NF-κB. Candidate ncRNAs, including circRNAs and lncRNAs, were identified as regulators of key genes like AKT2 and MITF, providing new mechanistic insights into F. nucleatum-associated inflammatory and systemic diseases.

Zhou, T., Meng, X., Wang, D., et al. Neutrophil Transcriptional Deregulation by the Periodontal Pathogen Fusobacterium nucleatum in Gastric Cancer: A Bioinformatic Study. Dis. Markers 2022, 9584507 (2022). doi:10.1155/2022/9584507.
Bioinformatic analysis identified 36 link genes connecting F. nucleatum-induced neutrophil transcriptional changes with gastric cancer, implicating intracellular trafficking, membrane-bound organelle dysfunction, transcription factors ER71/Sp1, and miRNAs miR580/miR155 in pathogenesis.

Zhou, Y., et al. Noncanonical activation of β-catenin by Porphyromonas gingivalis. Infection and Immunity 83, 8 (2015). doi:10.1128/IAI.00302-15
P. gingivalis activates β-catenin signaling via gingipain-mediated proteolysis, promoting epithelial cell proliferation, which may contribute to tumorigenesis.