West Kazakhstan Medical Journal

ISSN: 2707-6180 (Print) 2707-6199 (Online)

Pioneering research advancing the frontiers of medical knowledge and healthcare practices.

Association Mechanisms Between Periodontal Diseases and Systemic Pathology

Published date: Jun 02 2025

Journal Title: West Kazakhstan Medical Journal

Issue title: West Kazakhstan Medical Journal: Volume 67 Issue 2

Pages: 162 - 176

DOI: 10.18502/wkmj.v67i2.18748

Authors:

Madina A. Kurmanalinamadina83203@gmail.comDepartment of Dental Disciplines and Maxillofacial Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe

Dono M. Alimovastom_81@bk.ruDepartment of Faculty Therapeutic Dentistry, Tashkent State Dental Institute, Tashkent

Justyna Otulakowska-SkrzyńskaDepartment of Integrated Dentistry, Poznan University of Medical Sciences

Elnara K. IsmagulovaIsmagulova_e@mail.ruDepartments of Otolaryngology and Ophthalmology, West Kazakhstan Marat Ospanov Medical University, Aktobe

Bakyt S. Zhanalinazhanalina57@mail.ruDepartment of Dental Disciplines and Maxillofacial Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe

Aruzhan M. Aitmukhanbetovaaittmukhanbetova@gmail.comDepartment of Dental Disciplines and Maxillofacial Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe

Abstract:

Periodontitis is a chronic inflammatory disease caused by a dysbiotic oral microbiome and an altered immune response. It affects approximately 10% of the adult population and is one of the leading causes of tooth loss. Beyond its local consequences, periodontitis is closely associated with systemic diseases, including cardiovascular disorders, type 2 diabetes, rheumatoid arthritis, osteoporosis, chronic kidney disease, Alzheimer’s disease, pneumonia, pregnancy complications, and COVID-19. The main mechanisms underlying this relationship include chronic systemic inflammation, the spread of bacteria and their toxins through the bloodstream, and the activation of immune cells capable of exacerbating inflammation in other organs. For instance, bacterial lipopolysaccharides (LPS) and periodontopathogens such as Porphyromonas gingivalis can contribute to the development of atherosclerosis, endotoxemia, and autoimmune reactions. Further clinical studies are required to establish a causal relationship and develop effective treatment strategies. A deeper understanding of these mechanisms may facilitate the development of interdisciplinary approaches to the prevention and treatment of both periodontitis and related systemic diseases.

Keywords: periodontitis, cardiovascular diseases, rheumatoid arthritis, chronic renal insufficiency, Alzheimer’s disease, COVID-19

References:

[1] Hajishengallis G, Lamont RJ, Koo H. Oral polymicrobial communities: Assembly, function, and impact on diseases. Cell Host Microbe. 2023 Apr;31(4):528–538. https://doi.org/10.1016/j.chom.2023.02.009 PMID:36933557

[2] Caetano AJ, Yianni V, Volponi A, Booth V, D’Agostino EM, Sharpe P. Defining human mesenchymal and epithelial heterogeneity in response to oral inflammatory disease. eLife. 2021 Jan;10:e62810. https://doi.org/10.7554/eLife.62810 PMID:33393902

[3] Wu L, Zhang SQ, Zhao L, Ren ZH, Hu CY. Global, regional, and national burden of periodontitis from 1990 to 2019: Results from the global burden of disease study 2019. J Periodontol. 2022 Oct;93(10):1445–1454. https://doi.org/10.1002/JPER.21-0469 PMID:35305266

[4] Pupovac A, Kuiš D, Mišković I, Prpić J. Impact of periodontal diseases on oral health-related quality of life: A study with a condition-specific questionnaire in Croatian population. Eur J Dent. 2024 Oct;18(4):1172–1178. https://doi.org/10.1055/s-0044-1785534 PMID:39102859

[5] Benzian H, Watt R, Makino Y, Stauf N, Varenne B. WHO calls to end the global crisis of oral health. Lancet. 2022 Dec;400(10367):1909–1910. https://doi.org/10.1016/S0140-6736(22)02322-4 PMID:36410360

[6] Botelho J, Machado V, Leira Y, Proença L, Chambrone L, Mendes JJ. Economic burden of periodontitis in the United States and Europe: An updated estimation. J Periodontol. 2022 Mar;93(3):373–379. https://doi.org/10.1002/JPER.21-0111 PMID:34053082

[7] Villoria GE, Fischer RG, Tinoco EM, Meyle J, Loos BG. Periodontal disease: A systemic condition. Periodontol 2000. 2024 Oct;96(1):7–19. https://doi.org/10.1111/prd.12616PMID:39494478

[8] Li L, Bao J, Chang Y, Wang M, Chen B, Yan F. Gut microbiota may mediate the influence of periodontitis on prediabetes. J Dent Res. 2021 Nov;100(12):1387–1396. https://doi.org/10.1177/00220345211009449 PMID:33899584

[9] Herrera D, Molina A, Buhlin K, Klinge B. Periodontal diseases and association with atherosclerotic disease. Periodontol 2000. 2020 Jun;83(1):66–89. https://doi.org/10.1111/prd.12302 PMID:32385870

[10] Slots J, Rams TE. Herpesvirus-Bacteria pathogenic interaction in juvenile (aggressive) periodontitis. A novel etiologic concept of the disease. Periodontol 2000. 2024 Feb;94(1):532–538. https://doi.org/10.1111/prd.12501 PMID:37345343

[11] Taylor LJ, Dothard MI, Rubel MA, Allen AA, Hwang Y, Roche AM, et al. Redondovirus diversity and evolution on global, individual, and molecular scales. J Virol. 2021;95(21):e0081721. https://doi.org/10.1128/JVI.00817-21.

[12] Nagao JI, Kishikawa S, Tanaka H, Toyonaga K, Narita Y, Negoro-Yasumatsu K, et al. Pathobiontresponsive Th17 cells in gut-mouth axis provoke inflammatory oral disease and are modulated by intestinal microbiome. Cell Rep. 2022 Sep;40(10):111314. https://doi.org/10.1016/j.celrep.2022.111314 PMID:36070692

[13] Sedghi LM, Bacino M, Kapila YL. Periodontal disease: The good, the bad, and the unknown. Front Cell Infect Microbiol. 2021 Dec;11:766944. https://doi.org/10.3389/fcimb.2021.766944PMID:34950607

[14] Yamazaki K, Kamada N. Exploring the oral-gut linkage: Interrelationship between oral and systemic diseases. Mucosal Immunol. 2024 Feb;17(1):147–153. https://doi.org/10.1016/j.mucimm.2023.11.006 PMID:38007003

[15] Chen YF, Zhan Q, Wu CZ, Yuan YH, Chen W, Yu FY, et al. Baseline HbA1c level influences the effect of periodontal therapy on glycemic control in people with type 2 diabetes and periodontitis: A systematic review on randomized controlled trails. Diabetes Ther. 2021 May;12(5):1249–1278. https://doi.org/10.1007/s13300-021-01000-6 PMID:33481189

[16] Kajikawa T, Mastellos DC, Hasturk H, Kotsakis GA, Yancopoulou D, Lambris JD, et al., editors. C3-targeted host-modulation approaches to oral inflammatory conditions. Seminars in Immunology. Elsevier; 2022.

[17] Hajishengallis G, Hasturk H, Lambris JD, Apatzidou DA, Belibasakis GN, Bostanci N, et al. C3-targeted therapy in periodontal disease: Moving closer to the clinic. Trends Immunol. 2021 Oct;42(10):856–864. https://doi.org/10.1016/j.it.2021.08.001PMID:34483038

[18] Haque MM, Yerex K, Kelekis-Cholakis A, Duan K. Advances in novel therapeutic approaches for periodontal diseases. BMC Oral Health. 2022 Nov;22(1):492. https://doi.org/10.1186/s12903-022- 02530-6 PMID:36380339

[19] Yu B, Wang CY. Osteoporosis and periodontal diseases—An update on their association and mechanistic links. Periodontol 2000. 2022 Jun;89(1):99–113. https://doi.org/10.1111/prd.12422PMID:35244945

[20] Grant WB, van Amerongen BM, Boucher BJ. Periodontal disease and other adverse health outcomes share risk factors, including dietary factors and vitamin D status. Nutrients. 2023 Jun;15(12):2787. https://doi.org/10.3390/nu15122787 PMID:37375691

[21] Hong SJ, Yang BE, Yoo DM, Kim SJ, Choi HG, Byun SH. Analysis of the relationship between periodontitis and osteoporosis/fractures: A cross-sectional study. BMC Oral Health. 2021 Mar;21(1):125. https://doi.org/10.1186/s12903-021-01496-1 PMID:33731091

[22] Bülow JM, Renz N, Haffner-Luntzer M, Fischer V, Schoppa A, Tuckermann J, et al. Complement receptor C5aR1 on osteoblasts regulates osteoclastogenesis in experimental postmenopausal osteoporosis. Front Endocrinol (Lausanne). 2022 Sep;13:1016057. https://doi.org/10.3389/fendo.2022.1016057 PMID:36246887

[23] Kobayashi T, Bartold PM. Periodontitis and periodontopathic bacteria as risk factors for rheumatoid arthritis: A review of the last 10 years. Jpn Dent Sci Rev. 2023 Dec;59:263–272. https://doi.org/10.1016/j.jdsr.2023.08.002 PMID:37674898

[24] Mustufvi Z, Twigg J, Kerry J, Chesterman J, Pavitt S, Tugnait A, et al. Does periodontal treatment improve rheumatoid arthritis disease activity? A systematic review. Rheumatol Adv Pract. 2022 Aug;6(2):rkac061. https://doi.org/10.1093/rap/rkac061 PMID:35993013

[25] Dolcezza S, Flores-Fraile J, Lobo-Galindo AB, Montiel-Company JM, Zubizarreta-Macho Á. Relationship between rheumatoid arthritis and periodontal disease—Systematic review and meta-analysis. J Clin Med. 2024 Dec;14(1):10. https://doi.org/10.3390/jcm14010010PMID:39797091

[26] Svärd A, LoMartire R, Martinsson K, Öhman C, Kastbom A, Johansson A. Presence and immunoreactivity of Aggregatibacter actinomycetemcomitans in rheumatoid arthritis. Pathogens. 2024 Apr;13(5):368. https://doi.org/10.3390/pathogens13050368 PMID:38787220

[27] Bonilla M, Martín-Morales N, Gálvez-Rueda R, Raya-Álvarez E, Mesa F. Impact of protein citrullination by periodontal pathobionts on oral and systemic health: A systematic review of preclinical and clinical studies. J Clin Med. 2024 Nov;13(22):6831. https://doi.org/10.3390/jcm13226831 PMID:39597974

[28] Wang S, Yan T, Zhang B, Chen Y, Li Z. Porphyromonas gingivalis vaccine: Antigens and mucosal adjuvants. Vaccines (Basel). 2024 Jun;12(6):619. https://doi.org/10.3390/vaccines12060619 PMID:38932348

[29] El-Awady AR, Elashiry M, Morandini AC, Meghil MM, Cutler CW. Dendritic cells a critical link to alveolar bone loss and systemic disease risk in periodontitis: Immunotherapeutic implications. Periodontol 2000. 2022 Jun;89(1):41–50. https://doi.org/10.1111/prd.12428PMID:35244951

[30] Lim Y, Kim HY, An SJ, Choi BK. Activation of bone marrow-derived dendritic cells and CD4+ T cell differentiation by outer membrane vesicles of periodontal pathogens. J Oral Microbiol. 2022 Sep;14(1):2123550. https://doi.org/10.1080/20002297.2022.2123550PMID:36312320

[31] Parsegian K, Randall D, Curtis M, Ioannidou E. Association between periodontitis and chronic kidney disease. Periodontol 2000. 2022 Jun;89(1):114–124. https://doi.org/10.1111/prd.12431PMID:35244955

[32] Serni L, Caroti L, Barbato L, Nieri M, Serni S, Cirami CL, et al. Association between chronic kidney disease and periodontitis. A systematic review and metanalysis. Oral Dis. 2023 Jan;29(1):40–50. https://doi.org/10.1111/odi.14062 PMID:34726333

[33] Randall D. The uraemic microbiome: Oral and gut dysbiosis in experimental uraemia. 2023. https://qmro.qmul.ac.uk/xmlui/handle/123456789/83952

[34] Onabanjo OA, Nwhator SO, Arogundade FA. Effect of non-surgical periodontal therapy on renal function among pre-dialysis chronic kidney disease patients. Clin Med Health Res J. 2023;3(4):489– 494. https://doi.org/10.18535/cmhrj.v3i4.211.

[35] Howroyd F, Chacko C, MacDuff A, Gautam N, Pouchet B, Tunnicliffe B, et al. Ventilatorassociated pneumonia: Pathobiological heterogeneity and diagnostic challenges. Nat Commun. 2024 Jul;15(1):6447. https://doi.org/10.1038/s41467-024-50805-z PMID:39085269

[36] Scannapieco FA, Giuliano KK, Baker D. Oral health status and the etiology and prevention of nonventilator hospital-associated pneumonia. Periodontol 2000. 2022 Jun;89(1):51–58. https://doi.org/10.1111/prd.12423 PMID:35244952

[37] Pussinen PJ, Kopra E, Pietiäinen M, Lehto M, Zaric S, Paju S, et al. Periodontitis and cardiometabolic disorders: The role of lipopolysaccharide and endotoxemia. Periodontol 2000. 2022 Jun;89(1):19–40. https://doi.org/10.1111/prd.12433 PMID:35244966

[38] Nannan M, Xiaoping L, Ying J. Periodontal disease in pregnancy and adverse pregnancy outcomes: Progress in related mechanisms and management strategies. Front Med (Lausanne). 2022 Oct;9:963956. https://doi.org/10.3389/fmed.2022.963956 PMID:36388896

[39] Sayeed G, Varghese SS. Treating periodontal disease for preventing adverse pregnancy outcomes: Overview of systematic reviews. J Datta Meghe Ins Med Sci Uni. 2022;17(4):975–983. https://doi.org/10.4103/jdmimsu.jdmimsu_438_22.

[40] Saadaoui M, Singh P, Al Khodor S. Oral microbiome and pregnancy: A bidirectional relationship. J Reprod Immunol. 2021 Jun;145:103293. https://doi.org/10.1016/j.jri.2021.103293PMID:33676065

[41] Bello-Corral L, Alves-Gomes L, Fernández-Fernández JA, Fernández-García D, Casado-Verdejo I, Sánchez-Valdeón L. Implications of gut and oral microbiota in neuroinflammatory responses in Alzheimer’s disease. Life Sci. 2023 Nov;333:122132. https://doi.org/10.1016/j.lfs.2023.122132 PMID:37793482

[42] Said KN, Al-Momani AM, Almaseeh JA, Marouf N, Shatta A, Al-Abdulla J, et al. Association of periodontal therapy, with inflammatory biomarkers and complications in COVID-19 patients: A case control study. Clin Oral Investig. 2022 Nov;26(11):6721–6732. https://doi.org/10.1007/s00784-022- 04631-6 PMID:35906340

[43] Bemquerer LM, Oliveira SR, de Arruda JA, Costa FP, Miguita L, Bemquerer AL, et al. Clinical, immunological, and microbiological analysis of the association between periodontitis and COVID-19: A case-control study. Odontology. 2024 Jan;112(1):208–220. https://doi.org/10.1007/s10266-023-00811-2 PMID:37058199