Open wide: Expanding horizons of the periodontal-systemic relationship

Periodontitis has been linked to many systemic conditions, including well-established connections like cardiovascular disease and diabetes mellitus and emerging associations including neurodegenerative conditions, cancers, autoimmune conditions, and gastrointestinal disorders. These links may occcur through microbial translocation, immune dysregulation, and chronic inflammatory burden.

Periodontitis is a multifactorial infectious and inflammatory disease initiated by oral dysbiosis, and the host inflammatory response results in the destruction of tooth‑supporting hard and soft tissues.¹ Periodontitis has been credibly linked to more than 57 systemic diseases and conditions, and recent research has expanded our understanding on the associations between periodontal disease and systemic conditions, including dementias, cancers, autoimmune diseases, and gastrointestinal conditions.^1-5

This review seeks to provide updates on the periodontal-systemic connection, including mechanistic insights and emerging therapeutic approaches.

Additional reading: Practical ways to implement oral-systemic wellness protocols in your daily practice

Epidemiology of periodontal disease

Periodontitis remains one of the most prevalent chronic diseases globally. Severe periodontitis affects approximately 10%–15% of adults, while moderate disease affects up to 50%.^6,7 Prevalence rates are higher for individuals who smoke, for males, and for individuals with lower access to dental health-care services.^6-8 Given the high prevalence of periodontitis, it is critical to understand its impact on systemic disease burden.

Mechanisms of periodontal-­systemic interaction

Periodontitis impacts systemic health through several underlying mechanisms: 1) direct impact of periodontal microbes on distant organ systems through bacteremias, 2) a common inflammatory burden and priming of the immune response, and 3) microbial and cellular crosstalk.^9-11 Periodontal pathogens can enter the bloodstream during routine activities like chewing and toothbrushing.^12-14 Such pathogens have been identified in atherosclerotic plaques, tumors, respiratory infections, and in the central nervous system of individuals with dementias.^12-14

Periodontitis contributes to systemic inflammation through elevated levels of proinflammatory mediators related to the local response to oral dysbiosis.^15,16 Periodontal inflammation has also been shown to result in immune cell priming in the gingiva, upregulating systemic inflammatory responses, including increased neutrophil hyperactivity and altered monocyte phenotypes.¹⁷ Further, emerging research suggests that oral dysbiosis can influence other microbial communities, including the gut and genitourinary tract.^18,19

Emerging evidence linking periodontal disease and systemic conditions

While long-standing data has demonstrated associations between periodontitis and conditions such as cardiovascular disease, type 2 diabetes mellitus, and pregnancy outcomes, emerging evidence also supports links between periodontitis and dementias, cancers, autoimmune disorders, and gastrointestinal diseases.^4,5,20-22

Neurodegenerative diseases

Recent findings suggest that both the inflammatory burden and specific periodontal pathogens may be associated with the development or progression of dementias.^21,23-25 P. gingivalis gingipains have been detected in human brain tissue in individuals with Alzheimer’s disease and dementia.²⁵ In animal models, oral dysbiosis and periodontal infection has been shown to accelerate amyloid‑β accumulation in brain tissue, and systemic inflammation from periodontitis may exacerbate neuroinflammatory pathways, leading to worsening dementia symptoms and disease progression.²⁶

Periodontitis and cancer

Periodontal pathogens and periodontal inflammatory burden have been linked to various types of cancer, including colorectal, pancreatic, gastric, oropharyngeal, and esophageal cancers.^27,28 F. nucleatum has been observed in colorectal tumor tissue and this bacteria has demonstrated the ability to promote tumor cell proliferation and immune evasion.^29,30 Periodontal pathogens have been associated with increased pancreatic and gastric cancer risk, possibly through systemic inflammation and microbial translocation.^31,32

Further, in oropharyngeal and esophageal cancers, chronic periodontal inflammation may contribute to carcinogenesis through nitrosamine formation, increased oxidative stress, and localized DNA damage.^33,34 Additionally, in a large-scale study, specific periodontal pathogens were associated with different forms of esophageal cancer—T. forsythia was associated with esophageal adenocarcinoma, while P. gingivalis was linked to squamous cell carcinoma.³⁵

Periodontitis and autoimmune diseases

Increased incidence of autoimmune conditions, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis, has been linked to preexisting periodontitis.^36,37 The link between RA and periodontitis is particularly intriguing due to the potential for P. gingivalis to initiate an autoimmune cascade.^38,39 P. gingivalis is capable of citrullinating host proteins, which may result in increases in anti‑citrullinated protein antibody (ACPA) formation, a potential driver of RA disease extent, severity, progression.^38,39

Periodontitis and gastrointestinal disease

The gum-gut axis has become a major research frontier. It has been widely identified that an association exists between oral and gut dysbiosis, and patients with Crohn’s disease exhibit increased rates of periodontitis compared to age-matched controls.⁴⁰ Underlying mechanisms may include oral bacteria translocation to the gut, shared immune dysregulation, and increased gut barrier dysfunction.⁴⁰ Oral pathogens can colonize the gut and induce colitis in animal models, which may be a proposed mechanism for the interaction between oral dysbiosis impacting the entire gastrointestinal tract.^41,42

Beyond mechanical therapy: Host modulation and proresolving mediators

Given the role of the host immune-inflammatory response in disease progression of periodontitis and the systemic impact of periodontitis, use of adjunctive host modulation and proresolving mediators can provide additional benefits for periodontal and overall health. Host modulation therapy aims to reduce destructive inflammatory responses rather than targeting bacteria alone.

An emerging area for adjunctive periodontal therapy includes specialized proresolving mediators (SPMs).^43,44 SPMs do not suppress inflammation; instead, they actively promote resolution by reducing neutrophil infiltration, enhancing macrophage‑mediated clearance, promoting tissue regeneration, and upregulating anti-inflammatory biologic mediators.^43,44 Early research suggests that resolvin‑based therapies may be effective adjuncts to mechanical periodontal therapy and can enhance clinical outcomes.^45,46

Adjunctive use of SPMs has also been shown to reduce systemic inflammatory marker levels beyond that seen with traditional periodontal therapies alone.^45,46 SPMs represent a promising future direction in periodontal therapy and may be particularly impactful for individuals who have both periodontitis and systemic conditions.⁴⁶

Periodontal-­systemic research directions

While we continue to expand our knowledge regarding the links between periodontal disease and systemic conditions, there is still much that we do not know. Big data and specific molecular and microbial assays will allow us to further identify the role that systemic disease may play in periodontal disease progression and successful periodontal treatment. Conversely, we may also better understand the impact of periodontitis on systemic disease progression and therapies.

Conclusion

Emerging evidence demonstrates links between periodontitis and dementias, cancer, autoimmune diseases, and gastrointestinal disorders. Advances in host modulation and proresolving mediators offer promising therapeutic avenues. The interaction between oral and overall health underscores the importance of early periodontal diagnosis and treatment to promote optimal wellness for all patients. 

Additional reading: Rethinking periodontal care: A medical condition with a dental solution

Editor's note: This article appeared in the May 2026 print edition of Dental Economics magazine. Dentists in North America are eligible for a complimentary print subscription. Sign up here.

References

1. Monsarrat P, Blaizot A, Kémoun P, et al. Clinical research activity in periodontal medicine: a systematic mapping of trial registers. J Clin Periodontol. 2016;43(5):390-400. doi:10.1111/jcpe.12534
2. Siripaiboonpong N, Sharma P, Suvan J, D'Aiuto F. Associations between periodontal health status and multimorbidity: analysis of the UK biobank dataset. Study based on data from 500,000+ UK Biobank participants. Abstract 1235 (Oral Presentation).
3. Lockhart PB, Bolger AF, Papapanou PN, et al. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association? A scientific statement from the American Heart Association. 2012;125(20):2520-2544. doi:10.1161/CIR.0b013e31825719f3
4. Kapila YL. 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. 2021;87(1):11-16. doi:10.1111/prd.12398
5. Genco RJ, Sanz M. Clinical and public health implications of periodontal and systemic diseases: an overview. Periodontol 2000. 2020;83(1):7-13. doi:10.1111/prd.12344
6. Wu L, Huang CM, Wang Q, Wei J, Xie L, Hu CY. Burden of severe periodontitis: new insights based on a systematic analysis from the Global Burden of Disease Study 2021. BMC Oral Health. 2025;25(1):861. doi:10.1186/s12903-025-06271-0
7. Germen M, Baser U, Lacin CC, Fıratlı E, İşsever H, Yalcin F. Periodontitis prevalence, severity, and risk factors: a comparison of the AAP/CDC case definition and the EFP/AAP classification. Int J Environ Res Public Health. 2021;18(7): 3459. doi:10.3390/ijerph18073459
8. Eke PI, Thornton-Evans GO, Wei L, Borgnakke WS, Dye BA, Genco RJ. Periodontitis in US adults: National Health and Nutrition Examination Survey 2009–2014. J Am Dent Assoc. 2018;149(7):576-588. doi:10.1016/j.adaj.2018.04.023
9. Tattar R, da Costa BDC, Neves VCM. The interrelationship between periodontal disease and systemic health. Br Dent J. 2025;239(2):103-108. doi:10.1038/s41415-025-8642-2
10. Hajishengallis G, Chavakis T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat Rev Immunol. 2021;21(7):426-440. doi:10.1038/s41577-020-00488-6
11. Wu Z, Zhang Y, Wang L, et al. Periodontitis and systemic diseases: insights into the correlation, mechanisms, and clinical implications. Front Immunol. 2026;17:1777955. doi:10.3389/fimmu.2026.1777955
12. Foroughi M, Torabinejad M, Angelov N, et al. Bridging oral and systemic health: exploring pathogenesis, biomarkers, and diagnostic innovations in periodontal disease. 2025;53(6):2277-2302. doi:10.1007/s15010-025-02568-y
13. Horliana AC, Chambrone L, Foz AM, et al. Dissemination of periodontal pathogens in the bloodstream after periodontal procedures: a systematic review. PLoS One. 2014;9(5):e98271. doi:10.1371/journal.pone.0098271
14. Emery DC, Cerajewska TL, Seong J, et al. Comparison of blood bacterial communities in periodontal health and periodontal disease. Front Cell Infect Microbiol. 2021;10:577485. doi:10.3389/fcimb.2020.577485
15. Martínez-García M, Hernández-Lemus E. Periodontal inflammation and systemic diseases: an overview. Front Physiol. 2021;12:709438. doi:10.3389/fphys.2021.709438
16. Tonetti MS, Jepsen S, Jin L, Otomo-Corgel J. Impact of the global burden of periodontal diseases on health, nutrition and wellbeing of mankind: a call for global action. J Clin Periodontol. 2017;44(5):456-462. doi:10.1111/jcpe.12732
17. Fine N, Chadwick JW, Sun C, et al. Periodontal inflammation primes the systemic innate immune response. J Dent Res. 2021;100(3):318-325. doi:10.1177/0022034520963710
18. Gan G, Chen R, Zheng P, et al. Oral pathogens meet the gut microbiome: new mechanistic insights on systemic disease. Front Cell Infect Microbiol. 2026;15:1673512. doi:10.3389/fcimb.2025.1673512
19. Tan X, Wang Y, Gong T. The interplay between oral microbiota, gut microbiota and systematic diseases. J Oral Microbiol. 2023;15(1):2213112. doi:10.1080/20002297.2023.2213112
20. Isola G, Polizzi A, Serra S, Boato M, Sculean A. Relationship between periodontitis and systemic diseases: a bibliometric and visual study. Periodontol 2000. 2025;98(1):228-240. doi:10.1111/prd.12621
21. Chalmers JC, Hernandez-Kapila YL. The role of the oral microbiome, host response, and periodontal disease treatment in Alzheimer's disease: a primer. Periodontol 2000. 2025;98(1):220-227. doi:10.1111/prd.12631
22. Villoria GEM, Fischer RG, Tinoco EMB, Meyle J, Loos BG. Periodontal disease: a systemic condition. Periodontol 2000. 2024;96(1):7-19. doi:10.1111/prd.12616
23. Ryder MI. Porphyromonas gingivalis and Alzheimer disease: recent findings and potential therapies. J Periodontol. 2020;91(Suppl 1):S45-S49. doi:10.1002/JPER.20-0104
24. Ryder MI, Xenoudi P. Alzheimer disease and the periodontal patient: new insights, connections, and therapies. Periodontol 2000. 2021;87(1):32-42. doi:10.1111/prd.12389
25. Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer's disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333. doi:10.1126/sciadv.aau3333
26. Li X, Kiprowska M, Kansara T, Kansara P, Li P. Neuroinflammation: a distal consequence of periodontitis. J Dent Res. 2022;101(12):1441-1449. doi:10.1177/00220345221102084
27. Xiong J, Liu H, Li C, Li Y, Feng J. Linking periodontitis with 20 cancers, emphasis on oropharyngeal cancer: a Mendelian randomization analysis. Sci Rep. 2024;14(1):12511. doi:10.1038/s41598-024-63447-4
28. Duan C, Wan W, Tureke M, et al. Periodontal disease and incidence of cancers: a systematic review and meta-analysis of cohort studies. Int Dent J. 2026;76(3):109527. doi:10.1016/j.identj.2026.109527
29. Risoen KR, Shaw CA, Chien J, Weimer BC. Fusobacterium nucleatum and its impact on colorectal cancer chemoresistance: a meta-analysis of in vitro co-culture infections. Cancers (Basel). 2025;17(19):3247. doi:10.3390/cancers17193247
30. Galasso L, Termite F, Mignini I, et al. Unraveling the role of Fusobacterium nucleatum in colorectal cancer: molecular mechanisms and pathogenic insights. Cancers (Basel). 2025;17(3):368. doi:10.3390/cancers17030368
31. Márquez-Arrico CF, Silvestre FJ, Marquez-Arrico JE, Silvestre-Rangil J. Could periodontitis increase the risk of suffering from pancreatic cancer? A systematic review. Cancers (Basel). 2024;16(7):1257. doi:10.3390/cancers16071257
32. Baima G, Ribaldone DG, Romano F, Aimetti M, Romandini M. The gum-gut axis: periodontitis and the risk of gastrointestinal cancers. Cancers (Basel). 2023;15(18):4594. doi:10.3390/cancers15184594
33. Chauca-Bajaña L, Sánchez Arteaga BA, Ordóñez Balladares A, et al. Periodontitis and oral and oropharyngeal cancer risk: a systematic review and meta-analysis with exploratory evidence on tumor-associated Porphyromonas gingivalis. Dent J (Basel). 2026;14(2):80. doi:10.3390/dj14020080
34. Li T-J, Hao Y, Tang Y, Liang X. Periodontal pathogens: a crucial link between periodontal diseases and oral cancer. Front Microbiol. 2022;13:919633. doi:10.3389/fmicb.2022.919633
35. Peters B, Wu, J, Pei Z, et al. Oral microbiome composition reflects prospective risk for esophageal cancers. Cancer Res. 2017;77(23):6777–6787. doi:10.1158/0008-5472.CAN-17-1296
36. Rutter-Locher Z, Smith TO, Giles I, Sofat N. Association between systemic lupus erythematosus and periodontitis: a systematic review and meta-analysis. Front Immunol. 2017;8:1295. doi:10.3389/fimmu.2017.01295
37. Krutyhołowa A, Strzelec K, Dziedzic A, et al. Host and bacterial factors linking periodontitis and rheumatoid arthritis. Front Immunol. 2022;13:980805. doi:10.3389/fimmu.2022.980805
38. Mikuls TR, Payne JB, Reinhardt RA, et al. Antibody responses to Porphyromonas gingivalis ( gingivalis) in subjects with rheumatoid arthritis and periodontitis. Int Immunopharmacol. 2009;9(1):38-42. doi:10.1016/j.intimp.2008.09.008
39. Bartold PM, Lopez-Oliva I. Periodontitis and rheumatoid arthritis: an update 2012-2017. Periodontol 2000. 2020;83(1):189-212. doi:10.1111/prd.12300
40. Ozayzan FI, Albishri AA, Dallak AE, et al. Periodontitis and inflammatory bowel disease: a review. 2024;16(2):e54584. doi:10.7759/cureus.54584
41. Byrd KM, Gulati AS. The “gum-gut” axis in inflammatory bowel diseases: a hypothesis-driven review of associations and advances. Front Immunol. 2021;12:620124. doi:10.3389/fimmu.2021.620124
42. She Y, Kong X, Ge Y, et al. Periodontitis and inflammatory bowel disease: a meta-analysis. BMC Oral Health. 2020;20(1):67. doi:10.1186/s12903-020-1053-5
43. Sahni V, Van Dyke TE. Immunomodulation of periodontitis with SPMs. Front Oral Health. 2023;4:1288722. doi:10.3389/froh.2023.1288722
44. Osorio Parra MM, Elangovan S, Lee CT. Specialized pro-resolving lipid mediators in experimental periodontitis: a systematic review. Oral Dis. 2019;25(5):1265-1276. doi:10.1111/odi.12979
45. Alshibani N. Resolvins as a treatment modality in experimental periodontitis: a systematic review of preclinical studies. 2022;14(1):e21095. doi:10.7759/cureus.21095
46. de Molon RS, Steffens JP, de Avila ED, Teughels W, Van Dyke TE. Adjunctive therapies in periodontitis: current concepts and the future. J Periodontal Res. 2026;61(2):138-164. doi:10.1111/jre.70060