Porphyromonas gingivalis is a key periodontal pathogen in the relationship between periodontal and gastroenterological diseases

Periodontal diseases are among the most common human ailments. At the beginning of the 21st century, the concept of “periodontal medicine” emerged, examining the relationship between periodontal pathology and other diseases. Currently, over 50 different somatic diseases are associated with periodontal pathology. Among various periodontal microorganisms, Porphyromonas gingivalis is considered a key periodontopathogen, potentially correlating with systemic diseases. We searched the PubMed database for sources published before November 1, 2025, that examined the relationship between Porphyromonas gingivalis and the development of systemic diseases. Due to the large number of sources found (1,042), we narrowed the search to consider the relationship between Porphyromonas gingivalis and the development of gastrointestinal diseases (193 sources). This review examines the relationship between Porphyromonas gingivalis and inflammatory bowel diseases (48 references) and non-alcoholic fatty liver disease (44 references). The data presented in the review demonstrate that Porphyromonas gingivalis is involved in the development and progression of inflammatory bowel diseases through alterations in the intestinal microbiota along the mouth-gut axis, disruption of the intestinal barrier and permeability, release of inflammatory mediators, and impaired immune response. In non-alcoholic fatty liver disease, Porphyromonas gingivalis is detected in liver tissue. Furthermore, a connecting mouth-gut-liver axis is formed, and bacterial translocation of Porphyromonas gingivalis into the systemic circulation becomes important, accompanied by the circulation of inflammatory mediators and immune complexes, and disruption of metabolic, inflammatory, and immunological homeostasis. Oral health promotion should be considered as an integral part of a healthy lifestyle in order to reduce the burden of chronic non-communicable and communicable diseases

periodontitis, periodontal bacteria, Porphyromonas gingivalis, inflammatory bowel disease, non-alcoholic liver disease, comorbidity

1. Balta M.G., Papathanasiou E., Blix I.J., Van Dyke T.E. Host Modulation and Treatment of Periodontal Disease. J Dent Res. 2021 Jul;100(8):798-809. doi: 10.1177/0022034521995157.

2. O’Dwyer M.C., Furgal A., Furst W. et al. The Prevalence of Periodontitis Among US Adults with Multimorbidity Using NHANES Data 2011-2014. J Am Board Fam Med. 2023 Apr 3;36(2):313-324. doi:10.3122/jabfm.2022.220207R1.

3. Kassebaum N.J., Smith A.G.C., Bernabé E. et al. Global, regional, and national prevalence, incidence, and disability-adjusted life years for oral conditions for 195 countries, 1990-2015: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors. J Dent Res. 2017;96(4):380-7. doi: 10.1177/0022034517693566.

4. Williams R.C., Offenbacher S. Periodontal medicine: The emergence of a new branch of periodontology. Periodontology. 2000 2000, 23, 9-12 doi: 10.1034/j.1600-0757.2000.2230101.x.

5. Pai S.I., Matheus H.R., Guastaldi F.P.S. Effects of periodontitis on cancer outcomes in the era of immunotherapy. Lancet Healthy Longev. 2023 Apr;4(4): e166-e175. doi: 10.1016/S2666-7568(23)00021-1.

6. Klinicheskie rekomendatsii (protokoly lecheniya) pri diagnoze parodontit [Clinical recommen dations (treatment protocols) for the diagnosis of periodontitis]. (In Russ.) Available at: http://www.e-sto matology.ru/director/protokols_30-09-2014. (Accessed Date: 2025, Oct. 31).@@ Клинические рекомендации (протоколы лечения) при диагнозе пародонтит. URL: http://www.e-stomatology.ru/director/protokols_30-09-2014/

7. Van Dyke T.E., Starr J.R. Unraveling the link between periodontitis and cardiovascular disease. J Am Heart Assoc. 2013 Dec 16;2(6): e000657. doi: 10.1161/JAHA.113.000657.

8. Badran Z., Struillou X., Verner C. et al. Periodontitis as a risk factor for systemic disease: Are microparticles the missing link? Med Hypotheses. 2015 Jun;84(6):555-6. doi: 10.1016/j.mehy.2015.02.013.

9. 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. doi: 10.1016/bs.apcsb.2019.12.001.

10. Borsa L., Dubois M., Sacco G., Lupi L. Analysis the link between periodontal diseases and Alzheimer’s disease: A systematic review.Int J Environ Res Public Health. 2021;18(17):9312. doi: 10.3390/ijerph18179312.

11. Socransky S.S., Haffajee A.D., Cugini M.A. et al. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25(2):134-44. doi: 10.1111/j.1600-051x.1998.tb02419.x.

12. 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. 2010;21(4):496-502. doi: 10.1016/j.ejim.2010.07.011.

13. Li X., Kolltveit K.M., Tronstad L., Olsen I. Systemic diseases caused by oral infection. Clin Microbiol Rev. 2000;13:547-558. doi: 10.1128/CMR.13.4.547.

14. Yamazaki K. Oral-gut axis as a novel biological mechanism linking periodontal disease and systemic diseases: A review. Jpn Dent Sci Rev. 2023 Dec;59:273-280. doi: 10.1016/j.jdsr.2023.08.003.

15. Yilmaz Ö. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay. Microbiology (Reading). 2008 Oct;154(Pt 10):2897-2903. doi: 10.1099/mic.0.2008/021220-0.

16. Olsen I., Lambris J.D., Hajishengallis G. Porphyromonas gingivalis disturbs host-commensal homeostasis by changing complement function. J Oral Microbiol. 2017 Jun 30;9(1):1340085. doi: 10.1080/20002297.2017.1340085.

17. Chopra A., Bhat S.G., Sivaraman K. Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update. J Oral Microbiol. 2020 Aug 3;12(1):1801090. doi: 10.1080/20002297.2020.1801090.

18. 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. doi: 10.1016/bs.apcsb.2019.12.001.

19. Bostanci N., Belibasakis G.N. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett. 2012;333:1-9. doi: 10.1111/j.1574-6968.2012.02579.x.

20. Hajishengallis G., Darveau R.P., Curtis M.A. The keystone-pathogen hypothesis. Nat Rev Microbiol. 2012;10:717-725. doi: 10.1038/nrmicro2873.

21. Lira-Junior R., Figueredo C.M. Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions? World J Gastroenterol. 2016 Sep 21;22(35):7963-72. doi: 10.3748/wjg.v22.i35.7963.

22. Tanwar H., Gnanasekaran J.M., Allison D. et al. Unravelling the Oral-Gut Axis: Interconnection Between Periodontitis and Inflammatory Bowel Disease, Current Challenges, and Future Perspective. J Crohns Colitis. 2024 Aug 14;18(8):1319-1341. doi: 10.1093/ecco-jcc/jjae028.

23. Byrd K.M., Gulati A.S. The “Gum-Gut” Axis in Inflammatory Bowel Diseases: A Hypothesis-Driven Review of Associations and Advances. Front Immunol. 2021 Feb 19;12:620124. doi: 10.3389/fimmu.2021.620124.

24. Trukhan D.I., Sulimov A.F., Trukhan L.Y.Comorbidity of inflammatory bowel diseases and periodontal pathology. Meditsinskiy sovet = Medical Council. 2024;(15):215-223. (In Russ.) doi: 10.21518/ms2024-373.@@ Трухан Д.И., Сулимов А.Ф., Трухан Л.Ю. Коморбидность воспалительных заболеваний кишечника и патоло гии пародонта. Медицинский совет. 2024;18(15):215-223. doi: 10.21518/ms2024-373.

25. Brito F., de Barros F.C., Zaltman C. et al. Prevalence of periodontitis and DMFT index in patients with Crohn’s disease and ulcerative colitis. J Clin Periodontol. 2008 Jun;35(6):555-60. doi: 10.1111/j.1600-051X.2008.01231.x.

26. Habashneh R.A., Khader Y.S., Alhumouz M.K. et al. The association between inflammatory bowel disease and periodontitis among Jordanians: a case-control study. J Periodontal Res. 2012 Jun;47(3):293-8. doi: 10.1111/j.1600-0765.2011.01431.x.

27. Vavricka S.R., Manser C.N., Hediger S. et al. Periodontitis and gingivitis in inflammatory bowel disease: a case-control study. Inflamm Bowel Dis. 2013 Dec;19(13):2768-77. doi: 10.1097/01.MIB.0000438356.84263.3b.

28. Koutsochristou V., Zellos A., Dimakou K. et al. Dental Caries and Periodontal Disease in Children and Adolescents with Inflammatory Bowel Disease: A Case-Control Study. Inflamm Bowel Dis. 2015 Aug;21(8):1839-46. doi: 10.1097/MIB.0000000000000452.

29. Chi Y.C., Chen J.L., Wang L.H. et al. Increased risk of periodontitis among patients with Crohn’s disease: a population-based matched-cohort study.Int J Colorectal Dis. 2018 Oct;33(10):1437-1444. doi: 10.1007/s00384-018-3117-4.

30. Yu H.C., Chen T.P., Chang Y.C. Inflammatory bowel disease as a risk factor for periodontitis under Taiwanese National Health Insurance Research database. J Dent Sci. 2018 Sep;13(3):242-247. doi: 10.1016/j.jds.2018.03.004.

31. Zhang L., Gao X., Zhou J. et al. Increased risks of dental caries and periodontal disease in Chinese patients with inflammatory bowel disease.Int Dent J. 2020 Jun;70(3):227-236. doi: 10.1111/idj.12542.

32. Bertl K., Burisch J., Pandis N. et al. Periodontitis prevalence in patients with ulcerative colitis and Crohn’s disease - PPCC: A case-control study. J Clin Periodontol. 2022 Dec;49(12):1262-1274. doi: 10.1111/jcpe.13615.

33. Baima G., Muwalla M., Testa G. et al. Periodontitis prevalence and severity in inflammatory bowel disease: A case-control study. J Periodontol. 2023 Mar;94(3):313-322. doi: 10.1002/JPER.22-0322.

34. Papageorgiou S.N., Hagner M., Nogueira A.V. et al. Inflammatory bowel disease and oral health: systematic review and a meta-analysis. J Clin Periodontol. 2017 Apr;44(4):382-393. doi: 10.1111/jcpe.12698.

35. She Y.Y., Kong X.B., Ge Y.P. et al. Periodontitis and inflammatory bowel disease: a meta-analysis. BMC Oral Health. 2020 Mar 12;20(1):67. doi: 10.1186/s12903-020-1053-5.

36. Zhang Y., Qiao D., Chen R. et al. The Association between Periodontitis and Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. Biomed Res Int. 2021 Mar 12;2021:6692420. doi: 10.1155/2021/6692420.

37. Lorenzo-Pouso A.I., Castelo-Baz P., Rodriguez-Zorrilla S. et al. Association between periodontal disease and inflammatory bowel disease: a systematic review and meta-analysis. Acta Odontol Scand. 2021 Jul;79(5):344-353. doi: 10.1080/00016357.2020.1859132.

38. Domokos Z., Uhrin E., Szabó B. et al. Patients with inflammatory bowel disease have a higher chance of developing periodontitis: A systematic review and meta-analysis. Front Med (Lausanne). 2022 Nov 8;9:1020126. doi: 10.3389/fmed.2022.1020126.

39. Naghsh N., Karimi F., Tarrahi M.J., Rahimi A. Evaluation of the association between periodontitis and inflammatory bowel disease: A systematic review and Meta-analysis. BMC Gastroenterol. 2025 Aug 18;25(1):594. doi: 10.1186/s12876-025-04181-7.

40. Wang Z., Li S., Tan D. et al. Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study. J Clin Periodontol. 2023 Jun;50(6):736-743. doi: 10.1111/jcpe.13782.

41. Zhang Y., Bian C., Yu C. et al. Bidirectional association between oral diseases caused by plaque and the inflammatory bowel disease: A systematic review and meta-analysis. Jpn Dent Sci Rev. 2025 Dec;61:7-21. doi: 10.1016/j.jdsr.2025.02.001.

42. Lin C.Y., Tseng K.S., Liu J.M. et al. Increased Risk of Ulcerative Colitis in Patients with Periodontal Disease: A Nationwide Population-Based Cohort Study.Int J Environ Res Public Health. 2018 Nov 21;15(11):2602. doi: 10.3390/ijerph15112602.

43. Kang E.A., Chun J., Kim J.H. et al. Periodontitis combined with smoking increases risk of the ulcerative colitis: A national cohort study. World J Gastroenterol. 2020 Oct 7;26(37):5661-5672. doi: 10.3748/wjg.v26.i37.5661.

44. Imai J., Ichikawa H., Kitamoto S. et al. A potential pathogenic association between periodontal disease and Crohn’s disease. JCI Insight. 2021 Dec 8;6(23): e148543. doi: 10.1172/jci.insight.148543.

45. Živić M., Zdravković N., Stojanović B. et al. Association of Periodontal Disease with Activity of Crohn’s Disease. Medicina (Kaunas). 2023 Dec 12;59(12):2154. doi: 10.3390/medicina59122154.

46. Zilberstein N.F., Engen P.A., Swanson G.R. et al. The Bidirectional Effects of Periodontal Disease and Oral Dysbiosis on Gut Inflammation in Inflammatory Bowel Disease. J Crohns Colitis. 2025 Apr 4;19(4): jjae162. doi: 10.1093/ecco-jcc/jjae162.

47. Cai Z., Zhu T., Liu F. et al. Co-pathogens in Periodontitis and Inflammatory Bowel Disease. Front Med (Lausanne). 2021 Sep 20;8:723719. doi: 10.3389/fmed.2021.723719.

48. Lam G.A., Albarrak H., McColl C.J. et al. The Oral-Gut Axis: Periodontal Diseases and Gastrointestinal Disorders. Inflamm Bowel Dis. 2023 Jul 5;29(7):1153-1164. doi: 10.1093/ibd/izac241.

49. Jia L., Wu R., Han N. et al. Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2. Clin Transl Immunology. 2020 Nov 24;9(11): e1213. doi: 10.1002/cti2.1213.

50. Zhao X., Liu J., Zhang C. et al. Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase.Int J Oral Sci. 2021 Sep 30;13(1):31. doi: 10.1038/s41368-021-00136-2.

51. González-Febles J., Sanz M. Periodontitis and rheumatoid arthritis: What have we learned about their connection and their treatment? Periodontol. 2000. 2021 Oct;87(1):181-203. doi: 10.1111/prd.12385.

52. Krutyhołowa A., Strzelec K., Dziedzic A. et al. Host and bacterial factors linking periodontitis and rheumatoid arthritis. Front Immunol. 2022;13 doi: 10.3389/fimmu.2022.980805.

53. Koziel J., Mydel P., Potempa J. The link between periodontal disease and rheumatoid arthritis: an updated review. Curr Rheumatol Rep. 2014 Mar;16(3):408. doi: 10.1007/s11926-014-0408-9.

54. de Molon R.S., Rossa C. Jr., Thurlings R.M. et al. Linkage of Periodontitis and Rheumatoid Arthritis: Current Evidence and Potential Biological Interactions.Int J Mol Sci. 2019 Sep 13;20(18):4541. doi: 10.3390/ijms20184541.

55. Koutroubakis I.E., Karmiris K., Bourikas L. et al. Antibodies against cyclic citrullinated peptide (CCP) in inflammatory bowel disease patients with or without arthritic manifestations. Inflamm Bowel Dis. 2007 Apr;13(4):504-5. doi: 10.1002/ibd.20038.

56. Wegner N., Lundberg K., Kinloch A. et al. J. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev. 2010 Jan;233(1):34-54. doi: 10.1111/j.0105-2896.2009.00850.x.

57. Drury B., Hardisty G., Gray R.D., Ho G.T. Neutrophil Extracellular Traps in Inflammatory Bowel Disease: Pathogenic Mechanisms and Clinical Translation. Cell Mol Gastroenterol Hepatol. 2021;12(1):321-333. doi: 10.1016/j.jcmgh.2021.03.002.

58. Dos Santos Ramos A., Viana G.C.S., de Macedo Brigido M., Almeida J.F. Neutrophil extracellular traps in inflammatory bowel diseases: Implications in pathogenesis and therapeutic targets. Pharmacol Res. 2021 Sep;171:105779. doi: 10.1016/j.phrs.2021.105779.

59. Jia L., Jiang Y., Wu L. et al. Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis. Nat Commun. 2024 Feb 22;15(1):1617. doi: 10.1038/s41467-024-45473-y.

60. Tsuzuno T., Takahashi N., Yamada-Hara M. et al. Ingestion of Porphyromonas gingivalis exacerbates colitis via intestinal epithelial barrier disruption in mice. J Periodontal Res. 2021 Apr;56(2):275-288. doi: 10.1111/jre.12816.

61. Sohn J., Li L., Zhang L. et al. Porphyromonas gingivalis indirectly elicits intestinal inflammation by altering the gut microbiota and disrupting epithelial barrier function through IL9-producing CD4+ T cells. Mol Oral Microbiol. 2022 Apr;37(2):42-52. doi: 10.1111/omi.12359.

62. Arimatsu K., Yamada H., Miyazawa H. et al. Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep. 2014;4:4828. doi: 10.1038/srep04828.

63. Nakajima M., Arimatsu K., Kato T. et al. Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver. PLoS One. 2015;10: e0134234. doi: 10.1371/journal.pone.0134234.

64. Qi Y., Wu H.M., Yang Z. et al. New Insights into the Role of Oral Microbiota Dysbiosis in the Pathogenesis of Inflammatory Bowel Disease. Dig Dis Sci. 2022 Jan;67(1):42-55. doi: 10.1007/s10620-021-06837-2.

65. Lee Y.C., Liu C.Y., Lee C.L. et al. The Periodontopathic Pathogen, Porphyromonas gingivalis, Involves a Gut Inflammatory Response and Exacerbates Inflammatory Bowel Disease. Pathogens. 2022 Jan 11;11(1):84. doi: 10.3390/pathogens11010084.

66. Zhou T., Xu W., Wang Q. et al. The effect of the “Oral-Gut” axis on periodontitis in inflammatory bowel disease: A review of microbe and immune mechanism associations. Front Cell Infect Microbiol. 2023 Feb 27;13:1132420. doi: 10.3389/fcimb.2023.1132420.

67. Kinashi Y., Hase K. Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity. Front Immunol. 2021 Apr 22;12:673708. doi: 10.3389/fimmu.2021.673708.

68. Picchianti-Diamanti A., Rosado M.M., D’Amelio R. Infectious agents and inflammation: the role of microbiota in autoimmune arthritis. Front Microbiol. 2018;8 doi: 10.3389/fmicb.2017.02696.

69. Kobayashi T., Iwaki M., Nakajima A. et al. Current research on the pathogenesis of NAFLD/NASH and the gut-liver axis: Gut microbiota, dysbiosis, and leaky-gut syndrome.Int. J. Mol. Sci. 2022, 23, 11689 doi: 10.3390/ijms231911689.

70. Wang Y., Ma J., Wang H. et al. Mesalazine: a novel therapeutic agent for periodontitis via regulation of periodontal microbiota and inhibiting Porphyromonas gingivalis. Front Microbiol. 2025 Jan 22;16:1531258. doi: 10.3389/fmicb.2025.1531258.

71. Kobayashi R., Ogawa Y., Hashizume-Takizawa T., Kurita-Ochiai T. Oral bacteria affect the gut microbiome and intestinal immunity. Pathog Dis. 2020 Apr 1;78(3): ftaa024. doi: 10.1093/femspd/ftaa024.

72. Recharla N., Geesala R., Shi X.Z. Gut Microbial Metabolite Butyrate and Its Therapeutic Role in Inflammatory Bowel Disease: A Literature Review. Nutrients. 2023 May 11;15(10):2275. doi: 10.3390/nu15102275.

73. Seo Y., Oh S.J., Ahn J.S. et al. Implication of Porphyromonas gingivalis in colitis and homeostasis of intestinal epithelium. Lab Anim Res. 2019 Dec 4;35:26. doi: 10.1186/s42826-019-0029-6.

74. Carvalho-Filho P.C., Moura-Costa L.F., Pimentel A.C.M. et al. Apoptosis Transcriptional Profile Induced by Porphyromonas gingivalis Hmu Y. Mediators Inflamm. 2019 Mar 18;2019:6758159. doi: 10.1155/2019/6758159.

75. Fan R., Zhou Y., Chen X. et al. Porphyromonas gingivalis Outer Membrane Vesicles Promote Apoptosis via msRNA-Regulated DNA Methylation in Periodontitis. Microbiol Spectr. 2023 Feb 14;11(1): e0328822. doi: 10.1128/spectrum.03288-22.

76. Michielan A., D’Incà R.Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of leaky gut. Mediators Inflamm. 2015;2015:628157. doi: 10.1155/2015/628157.

77. Di Vincenzo F., Del Gaudio A., Petito V. et al. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review.Intern Emerg Med. 2024 Mar;19(2):275-293. doi: 10.1007/s11739-023-03374-w.

78. Groeger S., Jarzina F., Domann E., Meyle J. Porphyromonas gingivalis activates NFκB and MAPK pathways in human oral epithelial cells. BMC Immunol. 2017 Jan 5;18(1):1. doi: 10.1186/s12865-016-0185-5.

79. Huang X., Li Y., Zhang J., Feng Q. Linking Periodontitis with Inflammatory Bowel Disease through the Oral-Gut Axis: The Potential Role of Porphyromonas gingivalis. Biomedicines. 2024 Mar 19;12(3):685. doi: 10.3390/biomedicines12030685.

80. Akash H., Pandis N., Manschiebel W. et al. A Systematic Review and Meta-Analysis of Animal Models on the Possible Link Between Periodontitis and Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2025 Sep 1;31(9):2561-2583. doi: 10.1093/ibd/izaf087.

81. Trukhan D.I.Comorbidity of periodontal diseases and non-alcoholic fatty liver disease. Experimental and Clinical Gastroenterology. 2024;223(3): 14-24. (In Russ.) doi: 10.31146/1682-8658-ecg-223-3-14-24.@@ Трухан Д.И. Коморбидность заболеваний пародонта и неалкогольной жировой болезни печени. Экспериментальная и клиническая гастроэнтерология. 2024;223(3): 14-24. doi: 10.31146/1682-8658-ecg-223-3-14-24.

82. Akinkugbe A.A., Barritt A.S., Cai J. et al. Periodontitis and prevalence of elevated aminotransferases in the Hispanic Community Health Study/Study of Latinos. J Periodontol. 2018;89:949-958. doi: 10.1002/JPER.17-0579.

83. Akinkugbe A.A., Slade G.D., Barritt A.S. et al. Periodontitis and non-alcoholic fatty liver disease, a population-based cohort investigation in the Study of Health in Pomerania. J Clin Periodontol. 2017; 44: 1077-1087. doi: 10.1111/jcpe.12800.

84. Iwasaki T., Hirose A., Azuma T. et al. Correlation between ultrasound-diagnosed non-alcoholic fatty liver and periodontal condition in a cross-sectional study in Japan. Sci Rep. 2018;8:7496. doi: 10.1038/s41598-018-25857-z.

85. Helenius-Hietala J., Suominen A.L., Ruokonen H. et al. Periodontitis is associated with incident chronic liver disease-A population-based cohort study. Liver Int. 2019;39:583-591. doi: 10.1111/liv.13985.

86. Akinkugbe A.A., Avery C.L., Barritt A.S. et al. Do genetic markers of inflammation modify the relationship between periodontitis and nonalcoholic fatty liver disease? Findings from the SHIP study. J Dent Res. 2017; 96: 1392-1399. doi: 10.1177/0022034517720924.

87. Saito T., Shimazaki Y., Koga T. et al. Relationship between periodontitis and hepatic condition in Japanese women. J Int Acad Periodontol. 2006; 8: 89-95.

88. Furuta M., Ekuni D., Yamamoto T. et al. Relationship between periodontitis and hepatic abnormalities in young adults. Acta Odontol Scand. 2010 Jan;68(1):27-33. doi: 10.3109/00016350903291913.

89. Tan L., He Y., Wang T. et al. A Mendelian randomization study between chronic periodontitis and non-alcoholic fatty liver disease. J Periodontal Res. 2024 Apr;59(2):346-354. doi: 10.1111/jre.13218.

90. Qiao F., Li X., Liu Y. et al. Periodontitis and NAFLD-related diseases: A bidirectional two-sample Mendelian randomization study. Oral Dis. 2024 Jul;30(5):3452-3461. doi: 10.1111/odi.14785.

91. Kuraji R., Sekino S., Kapila Y., Numabe Y. Periodontal disease-related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral-liver axis. Periodontol. 2000 2021; 87: 204-240. doi: 10.1111/prd.12387.

92. Hujoel P.P., White B.A., García R.I., Listgarten M.A. The dentogingival epithelial surface area revisited. J Periodontal Res. 2001;36:48-55. doi: 10.1034/j.1600-0765.2001.00011.x.

93. Sharma S., Tiwari N., Tanwar S.S. The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis. Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep;398(9):11541-11579. doi: 10.1007/s00210-025-04069-z.

94. Kobayashi T., Iwaki M., Nakajima A. et al. Current research on the pathogenesis of NAFLD/NASH and the gut-liver axis: Gut microbiota, dysbiosis, and leaky-gut syndrome.Int. J. Mol. Sci. 2022, 23, 11689 doi: 10.3390/ijms231911689.

95. Mei E.H., Yao C., Chen Y.N. et al. Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease. World J Hepatol. 2024 May 27;16(5):688-702. doi: 10.4254/wjh.v16.i5.688.

96. Kuraji R., Sekino S., Kapila Y., Numabe Y. Periodontal disease-related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral-liver axis. Periodontol. 2000 2021; 87: 204-240. doi: 10.1111/prd.12387.

97. Ishikawa M., Yoshida K., Okamura H. et al. Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway. Biochim Biophys Acta. 2013; 1832: 2035-2043. doi: 10.1016/j.bbadis.2013.07.012.

98. Li Y., Lu Z., Zhang X. et al. Metabolic syndrome exacerbates inflammation and bone loss in periodontitis. J Dent Res. 2015;94:362-370. doi: 10.1177/0022034514561658.

99. Kuraji R., Fujita M., Ito H. et al. Effects of experimental periodontitis on the metabolic system in rats with diet-induced obesity (DIO): an analysis of serum biochemical parameters. Odontology. 2018;106:162-170. doi: 10.1007/s10266-017-0322-5.

100. Kuraji R., Ito H., Fujita M. et al. Porphyromonas gingivalis induced periodontitis exacerbates progression of non-alcoholic steatohepatitis in rats. Clin Exp Dent Res. 2016;2:216-225. doi: 10.1002/cre2.4.

101. Sasaki N., Katagiri S., Komazaki R. et al. Endotoxemia by Porphyromonas gingivalis Injection Aggravates Non-alcoholic Fatty Liver Disease, Disrupts Glucose/Lipid Metabolism, and Alters Gut Microbiota in Mice. Front Microbiol. 2018 Oct 24;9:2470. doi: 10.3389/fmicb.2018.02470.

102. Wu L., Shi R., Bai H. et al. Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk. Front Cell Infect Microbiol. 2022 Mar 10;12:776996. doi: 10.3389/fcimb.2022.776996.

103. Yoneda M., Naka S., Nakano K. et al. Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease. BMC Gastroenterol. 2012;12:16. doi: 10.1186/1471-230X-12-16.

104. Nakahara T., Hyogo H., Ono A. et al. Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease. J Gastroenterol. 2018 Feb;53(2):269-280. doi: 10.1007/s00535-017-1368-4.

105. Furusho H., Miyauchi M., Hyogo H. et al. Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice. J. Gastroenterol. 2013, 48, 1259-1270 doi: 10.1007/s00535-012-0738-1.

106. Zhu J., Jiang Z., Yu F. et al.Integrated oral-gut microbiota therapy: a novel perspective on preventing bacterial translocation for systemic disease management. Front Cell Infect Microbiol. 2025 Jul 28;15:1641816. doi: 10.3389/fcimb.2025.1641816.

107. Ahn J.S., Yang J.W., Oh S.J. et al. Porphyromonas gingivalis exacerbates the progression of fatty liver disease via CD36-PPARγ pathway. BMB Rep. 2021 Jun;54(6):323-328. doi: 10.5483/BMBRep.2021.54.6.050.

108. Yao C., Lan D., Li X. et al. Porphyromonas gingivalis triggers inflammation in hepatocyte depend on ferroptosis via activating the NF-κB signaling pathway. Oral Dis. 2024 Apr;30(3):1680-1694. doi: 10.1111/odi.14537.

109. Lv C., Shi K., Guo Y. et al. Emerging Roles of Periodontal Pathogen-Derived Outer Membrane Vesicles in NAFLD.Int Dent J. 2025 Aug;75(4):100825. doi: 10.1016/j.identj.2025.03.029.

110. Nagasaki A., Sakamoto S., Chea C. et al. Odontogenic infection by Porphyromonas gingivalis exacerbates fibrosis in NASH via hepatic stellate cell activation. Sci Rep. 2020 Mar 5;10(1):4134. doi: 10.1038/s41598-020-60904-8.

111. Kashiwagi Y., Aburaya S., Sugiyama N. et al. Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model. Sci Rep. 2021;11:18398. doi: 10.1038/s41598-021-97868-2.

112. Yamazaki K., Kato T., Tsuboi Y. et al. Oral Pathobiont-Induced Changes in Gut Microbiota Aggravate the Pathology of Nonalcoholic Fatty Liver Disease in Mice. Front Immunol. 2021;12:766170. doi: 10.3389/fimmu.2021.766170.

113. Wang T., Ishikawa T., Sasaki M., Chiba T. Oral and Gut Microbial Dysbiosis and Non-alcoholic Fatty Liver Disease: The Central Role of Porphyromonas gingivalis. Front Med (Lausanne). 2022 Mar 2;9:822190. doi: 10.3389/fmed.2022.822190.

114. Winning L., Patterson C.C., Cullen K.M. et al. The association between subgingival periodontal pathogens and systemic inflammation. J Clin Periodontol. 2015;42:799-806. doi: 10.1111/jcpe.12450.

115. Sato S., Kamata Y., Kessoku T. et al. A cross-sectional study assessing the relationship between non-alcoholic fatty liver disease and periodontal disease. Sci Rep. 2022;12:13621. doi: 10.1038/s41598-022-17917-2.

116. Nagasaki A., Sakamoto S., Arai T. et al. Elimination of Porphyromonas gingivalis inhibits liver fibrosis and inflammation in NASH. J Clin Periodontol. 2021 Oct;48(10):1367-1378. doi: 10.1111/jcpe.13523.

117. Forner L., Larsen T., Kilian M., Holmstrup P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. J Clin Periodontol. 2006 Jun;33(6):401-7. doi: 10.1111/j.1600-051X.2006.00924.x.

118. Martins C.C., Lockhart P.B., Firmino R.T. et al. Bacteremia following different oral procedures: Systematic review and meta-analysis. Oral Dis. 2024 Apr;30(3):846-854. doi: 10.1111/odi.14531.

119. Ricciardi R.M., Cipollone A., D’Ardes D. et al. Risk Factors and Immunoinflammatory Mechanisms Leading to Atherosclerosis: Focus on the Role of Oral Microbiota Dysbiosis. Microorganisms. 2023 Jun 1;11(6):1479. doi: 10.3390/microorganisms11061479.

120. Liu L., Geng Y., Xiong C. Impact of Porphyromonas gingivalis-odontogenic infection on the pathogenesis of non-alcoholic fatty liver disease. Ann Med. 2023;55(2):2255825. doi: 10.1080/07853890.2023.2255825.

121. Dominy S.S., 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 Jan 23;5(1): eaau3333. doi: 10.1126/sciadv.aau3333.