Porphyromonas Gingivalis in the Development of Periodontitis: Impact on Dysbiosis and Inflammation

Document Type : Review Article

Authors

1 Académie Internationale de Médecine Dentaire Intégrative, Paris, France

2 Inochi Care Private Limited, New Delhi-110017, India

3 Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University Multan, Pakistan

4 Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France

Abstract

Chronic periodontitis is an inflammatory disease of the dental plaque and affects the soft tissues supporting the tooth. It is one of the most practical oral health issues across the globe and adversely affects the quality of life. In a neutrophil-mediated action, the inflammatory response to periodontitis destroys the periodontal ligaments, gums, the alveolar bone, and the cementum. Some of the most associated invasive pathogens with periodontitis are Porphyromonas gingivalis, Aggregatibacter actinomycetecomitans, and Fusobacterium nucleatum. Google Scholar and PubMed were used to search the evidence using key terms like 'periodontitis,' 'Porphyromonas gingivalis,' 'Oral Dysbiosis and Periodontitis,' ‘Porphyromonas gingivalis and Periodontitis,' etc. Only studies were included reviewing the Porphyromonas gingivalis and its role in periodontitis. It has been observed from several oral pathogens that P. gingivalis has received immense attention due to a strong association between Porphyromonas gingivalis and periodontal disease. Porphyromonas gingivalis also disrupts the delicate balance between various members of the oral microbial communities and promotes oral dysbiosis. The dysbiotic state of the oral microbiome is distinct in functional capabilities and shows a higher expression of genes involved in lipopolysaccharide synthesis, energy regulation, and bacterial motility. Certain virulence factors such as gingipains, LPS, and fimbriae also increase the invasion and pathogenicity of Porphyromonas gingivalis. Its presence in the periodontal tissues increases the secretion of numerous pro-inflammatory mediators such as TNF-α, IL-8, and IL-1β, leading to the destruction of soft gingival tissues and ligaments. Early detection of periodontitis and immediate treatment can prevent soft tissue destruction and dentition loss. In conclusion, details about the oral microbiome, oral dysbiosis, and inflammation may offer new therapeutic options in the future, including a personalized approach and the use of combination therapy.

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Main Subjects


  1. Vos T, Abajobir AA, Abate KH, Abbafati C, Abbas KM, Abd-Allah F, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211-59.
  2. Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global prevalence of periodontal disease and lack of its surveillance. Sci World J. 2020;2020.
  3. Rafiei M, Kiani F, Sayehmiri F, Sayehmiri K, Sheikhi A, Azodi MZ. Study of Porphyromonas gingivalis in periodontal diseases: A systematic review and meta-analysis. Med J Islam Repub Iran. 2017;31:62.
  4. Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int J Health Sci. 2017;11(2):72.
  5. International. JOD. Retracted: Risk Factors of Periodontal Disease: Review of the Literature. Int J Dent. 2021;2021.
  6. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3(1):1-14.
  7. Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment. Clin Microbiol Rev. 2001;14(4):727-52.
  8. Winning L, Linden GJ. Periodontitis and systemic disease. BDJ Team. 2015;2:15163.
  9. Saremi A, Nelson RG, Tulloch-Reid M, Hanson RL, Sievers ML, Taylor GW, et al. Periodontal disease and mortality in type 2 diabetes. Diabetes Care. 2005;28(1):27-32.
  10. Borrell LN, Beck JD, Heiss G. Socioeconomic disadvantage and periodontal disease: the Dental Atherosclerosis Risk in Communities study. Am J Public Health. 2006;96(2):332-9.
  11. Baiju RMP, Peter E, Nayar BR, Varughese JM, Varghese NO. Prevalence and predictors of early periodontal disease among adolescents. J Indian Soc Periodontol. 2019;23(4):356.
  12. Tadjoedin FM, Fitri AH, Kuswandani SO, Sulijaya B, Soeroso Y. The correlation between age and periodontal diseases. J Int Dent Medical Res. 2017;10(2):327.
  13. Lertpimonchai A, Rattanasiri S, Vallibhakara SA-O, Attia J, Thakkinstian A. The association between oral hygiene and periodontitis: a systematic review and meta-analysis. Int Dent J. 2017;67(6):332-43.
  14. Kirch W. CPI (Community Periodontal Index). In: Kirch W, editor. Encyclopedia of Public Health. Dordrecht: Springer Netherlands; 2008. p. 176--7.
  15. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol. 2018;89:S159-S72.
  16. Preshaw PM. Detection and diagnosis of periodontal conditions amenable to prevention. BMC Oral Health. 2015;15(1):1-11.
  17. Jiao Y, Hasegawa M, Inohara N. The role of oral pathobionts in dysbiosis during periodontitis development. J Dent Res. 2014;93(6):539-46.
  18. Kirst ME, Li EC, Alfant B, Chi Y-Y, Walker C, Magnusson I, et al. Dysbiosis and alterations in predicted functions of the subgingival microbiome in chronic periodontitis. Appl Environ Microbiol. 2015;81(2):783-93.
  19. Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10(5):497-506.
  20. Ximénez‐Fyvie LA, Haffajee AD, Socransky SS. Microbial composition of supra‐and subgingival plaque in subjects with adult periodontitis. J Clin Periodontol. 2000;27(10):722-32.
  21. Tanner AC, Kent Jr R, Kanasi E, Lu SC, Paster BJ, Sonis ST, et al. Clinical characteristics and microbiota of progressing slight chronic periodontitis in adults. J Clin Periodontol. 2007;34(11):917-30.
  22. Yost S, Duran-Pinedo AE, Teles R, Krishnan K, Frias-Lopez J. Functional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis. Genome Med. 2015;7(1):1-19.
  23. Deng Z-L, Szafrański SP, Jarek M, Bhuju S, Wagner-Döbler I. Dysbiosis in chronic periodontitis: key microbial players and interactions with the human host. Sci Rep. 2017;7(1):1-13.
  24. Boyer E, Leroyer P, Malherbe L, Fong SB, Loréal O, Bonnaure Mallet M, et al. Oral dysbiosis induced by Porphyromonas gingivalis is strain-dependent in mice. J Oral Microbiol. 2020;12(1):1832837.
  25. Meuric V, Le Gall-David S, Boyer E, Acuña-Amador L, Martin B, Fong SB, et al. Signature of microbial dysbiosis in periodontitis. Appl Environ Microbiol. 2017;83(14):e00462-17.
  26. Payne M, Hashim A, Alsam A, Joseph S, Aduse-Opoku J, Wade WG, et al. Horizontal and vertical transfer of oral microbial dysbiosis and periodontal disease. J Dent Res. 2019;98(13):1503-10.
  27. Puig-Silla M, Dasí-Fernánde F, Montiel-Company J-M, Almerich-Silla J-M. Prevalence of fimA genotypes of Porphyromonas gingivalis and other periodontal bacteria in a Spanish population with chronic periodontitis. Med Oral Patol Oral Cir Bucal. 2012;17(6):1047.
  28. Xu W, Zhou W, Wang H, Liang S. Roles of Porphyromonas gingivalis and its virulence factors in periodontitis. Adv Protein Chem Struct Biol. 2020;120:45-84.
  29. Amano A, Nakamura T, Kimura S, Morisaki I, Nakagawa I, Kawabata S, et al. Molecular interactions of Porphyromonas gingivalis fimbriae with host proteins: kinetic analyses based on surface plasmon resonance. Infect Immun. 1999;67(5):2399-405.
  30. Metzger Z, Blasbalg J, Dotan M, Weiss EI. Enhanced attachment of Porphyromonas gingivalis to human fibroblasts mediated by Fusobacterium nucleatum. J Endod. 2009;35(1):82-5.
  31. Okuda T, Kokubu E, Kawana T, Saito A, Okuda K, Ishihara K. Synergy in biofilm formation between Fusobacterium nucleatum and Prevotella species. Anaerobe. 2012;18(1):110-6.
  32. Lamont RJ, Chan A, Belton CM, Izutsu KT, Vasel D, Weinberg A. Porphyromonas gingivalis invasion of gingival epithelial cells. Infect Immun. 1995;63(10):3878-85.
  33. Imamura T. The role of gingipains in the pathogenesis of periodontal disease. J Periodontol. 2003;74(1):111-8.
  34. Yilmaz Ö, Watanabe K, Lamont RJ. Involvement of integrins in fimbriae‐mediated binding and invasion by Porphyromonas gingivalis. Cell Microbiol. 2002;4(5):305-14.
  35. Mao S, Park Y, Hasegawa Y, Tribble GD, James CE, Handfield M, et al. Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis. Cell Microbiol. 2007;9(8):1997-2007.
  36. Yilmaz Oz, Jungas T, Verbeke P, Ojcius DM. Activation of the phosphatidylinositol 3-kinase/Akt pathway contributes to survival of primary epithelial cells infected with the periodontal pathogen Porphyromonas gingivalis. Infect Immun. 2004;72(7):3743-51.
  37. Boisvert H, Duncan MJ. Translocation of Porphyromonas gingivalis gingipain adhesin peptide A44 to host mitochondria prevents apoptosis. Infect Immun. 2010;78(8):3616-24.
  38. Stathopoulou PG, Galicia JC, Benakanakere MR, Garcia CA, Potempa J, Kinane DF. Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism. BMC Microbiol. 2009;9(1):1-12.
  39. Bugueno IM, Batool F, Keller L, Kuchler-Bopp S, Benkirane-Jessel N, Huck O. Porphyromonas gingivalis bypasses epithelial barrier and modulates fibroblastic inflammatory response in an in vitro 3D spheroid model. Sci Rep. 2018;8(1):1-13.
  40. Gao L, Ma Y, Li X, Zhang L, Zhang C, Chen Q, et al. Research on the roles of genes coding ATP‐binding cassette transporters in Porphyromonas gingivalis pathogenicity. J Cell Biochem. 2020;121(1):93-102.
  41. Kato Y, Hagiwara M, Ishihara Y, Isoda R, Sugiura S, Komatsu T, et al. TNF-α augmented Porphyromonas gingivalis invasion in human gingival epithelial cells through Rab5 and ICAM-1. BMC Microbiol. 2014;14(1):1-13.
  42. Geng F, Liu J, Guo Y, Li C, Wang H, Wang H, et al. Persistent exposure to Porphyromonas gingivalis promotes proliferative and invasion capabilities, and tumorigenic properties of human immortalized oral epithelial cells. Front Cell Infect Microbiol. 2017;7:57.
  43. Marsh PD, editor Dental plaque as a biofilm and a microbial community–implications for health and disease. BMC Oral health; 2006: BioMed Central.
  44. Deo PN, Deshmukh R. Oral microbiome: Unveiling the fundamentals. Journal of oral and maxillofacial pathology: JOMFP. 2019;23(1):122.
  45. Sharma N, Bhatia S, Sodhi AS, Batra N. Oral microbiome and health. AIMS microbiology. 2018;4(1):42.
  46. Marsh PD. Microbial ecology of dental plaque and its significance in health and disease. Adv Dental Res. 1994;8(2):263-71.
  47. Van Dyke TE, Bartold PM, Reynolds EC. The nexus between periodontal inflammation and dysbiosis. Front Immunol. 2020;11:511.
  48. Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol. 2014;35(1):3-11.
  49. Hajishengallis G. Dysbiosis and inflammation in periodontitis: synergism and implications for treatment. J Oral Microbiol. 2017;9(1):1325198.
  50. Sakanaka A, Kuboniwa M, Hashino E, Bamba T, Fukusaki E, Amano A. Distinct signatures of dental plaque metabolic byproducts dictated by periodontal inflammatory status. Sci Rep. 2017;7(1):1-10.
  51. Dutzan N, Kajikawa T, Abusleme L, Greenwell-Wild T, Zuazo CE, Ikeuchi T, et al. A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018;10(463).
  52. Abe K, Takahashi A, Fujita M, Imaizumi H, Hayashi M, Okai K, et al. Dysbiosis of oral microbiota and its association with salivary immunological biomarkers in autoimmune liver disease. PloS One. 2018;13(7):e0198757.
  53. Rai AK, Panda M, Das AK, Rahman T, Das R, Das K, et al. Dysbiosis of salivary microbiome and cytokines influence oral squamous cell carcinoma through inflammation. Arch Microbiol. 2021;203(1):137-52.
  54. Rodríguez-Lozano B, González-Febles J, Garnier-Rodríguez JL, Dadlani S, Bustabad-Reyes S, Sanz M, et al. Association between severity of periodontitis and clinical activity in rheumatoid arthritis patients: a case–control study. Arthritis Res Ther. 2019;21(1):1-12.
  55. Cheng Z, Meade J, Mankia K, Emery P, Devine DA. Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):19-30.
  56. Bogdanovska L, Kukeska S, Popovska M, Petkovska R, Goracinova K. Therapeutic strategies in the treatment of periodontitis. Biol Pharm Bull. 2012;58(1):2.
  57. Krayer JW, Leite RS, Kirkwood KL. Non-surgical chemotherapeutic treatment strategies for the management of periodontal diseases. Dent Clin. 2010;54(1):13-33.
  58. Kapoor A, Malhotra R, Grover V, Grover D. Systemic antibiotic therapy in periodontics. Dent Res J. 2012;9(5):505.
  59. Hirsch R, Deng H, Laohachai M. Azithromycin in periodontal treatment: more than an antibiotic. J Periodontal Res. 2012;47(2):137-48.
  60. Ong HS, Oettinger-Barak O, Dashper SG, Darby IB, Tan KH, Reynolds EC. Effect of azithromycin on a red complex polymicrobial biofilm. J Oral Microbiol. 2017;9(1):1339579.
  61. Suryaprasanna J, Radhika PL, Karunakar P, Rekharani K, Faizuddin U, Manojkumar MG, et al. Evaluating the effectiveness of clarithromycin as an adjunct to scaling and root planing: A randomized clinical trial. J Indian Soc Periodontol. 2018;22(6):529.
  62. Gulati M, Anand V, Govila V, Jain N. Host modulation therapy: An indispensable part of perioceutics. J Indian Soc Periodontol. 2014;18(3):282.
  63. Hasturk H, Kantarci A. Activation and resolution of periodontal inflammation and its systemic impact. Periodontology. 2015;69(1):255-73.
  64. Wang H-y, Lin L, Fu W, Yu H-Y, Yu N, Tan L-s, et al. Preventive effects of the novel antimicrobial peptide Nal-P-113 in a rat Periodontitis model by limiting the growth of Porphyromonas gingivalis and modulating IL-1β and TNF-α production. BMC Complement Altern Med. 2017;17(1):1-10.
  65. Batool F, Stutz C, Petit C, Benkirane-Jessel N, Delpy E, Zal F, et al. A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction. Sci Rep. 2020;10(1):1-14.
  66. Cheng R, Wu Z, Li M, Shao M, Hu T. Interleukin-1β is a potential therapeutic target for periodontitis: a narrative review. Int J Oral Sci. 2020;12(1):1-9.
  67. Martuscelli G, Fiorellini JP, Crohin CC, Howard Howell T. The effect of interleukin‐11 on the progression of ligature‐induced periodontal disease in the beagle dog. J
    Periodontol. 2000;71(4):573-8.
  68. Fawzy El-Sayed KM, Doerfer CE. Animal models for periodontal tissue engineering: a knowledge-generating process. Tissue Eng Part C. 2017;23(12):900-25.
  69. Goker F, Larsson L, Del Fabbro M, Asa’ad F. Gene delivery therapeutics in the treatment of periodontitis and peri-implantitis: a state of the art review. Int J Mol Sci. 2019;20(14):3551.
  1. Haze A, Taylor AL, Haegewald S, Leiser Y, Shay B, Rosenfeld E, et al. Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis. J Cell Mol Med. 2009;13(6):1110-24.
  2. Yoshida W, Takeuchi T, Imamura K, Seshima F, Saito A, Tomita S. Treatment of chronic periodontitis with recombinant human fibroblast growth factor-2 and deproteinized bovine bone mineral in wide intrabony defects: 12-month follow-up case series. Bull Tokyo Dent Coll. 2020;61(4):231-41.
  3. Tavelli L, Ravidà A, Barootchi S, Chambrone L, Giannobile W. Recombinant human platelet–derived growth factor: A systematic review of clinical findings in oral regenerative procedures. JDR Clin Trans Res. 2021;6(2):161-73.