Buy (150 RUB)
Generate QR code
Open Access
Subscription or Fee Access
Non-alcoholic fatty liver disease and periodontitis – clinical and pathogenetic relationships
https://doi.org/10.33667/2078-5631-2025-13-12-15
Abstract
Non-alcoholic fatty liver disease (NAFLD) and periodontitis have a number of common risk factors, such as obesity, insulin resistance (IR), and dyslipidemia, which contribute to the formation of systemic inflammation. The review articles notes that there is a bidirectional relationship between NAFLD and periodontitis, indicating that the formation of one disease can worsen the other. Today, NAFLD is considered as a systemic inflammation that can contribute to the progression of periodontitis by disrupting immune responses and exacerbating inflammatory processes in periodontal tissues. Human patients with NAFLD often have impaired lipid metabolism, which can affect the composition of the oral microbiota, leading to dysbiosis and increased susceptibility to periodontal diseases. Conversely, periodontitis is associated with the progression of NAFLD through mechanisms including systemic inflammation and oxidative stress. The formation of chronic periodontal inflammation can be accompanied by the release of pro-inflammatory cytokines and bacterial toxins into the bloodstream, which contributes to liver inflammation and exacerbates the course of liver steatosis. The relationship between NAFLD and periodontitis highlights the importance of comprehensive treatment strategies targeting both diseases.
About the Author
A. V. Akhmedov
Omsk State Medical University
Russian Federation
Russian Federation
И DM Sci (habil.), professor, head of Dept of Medical Rehabilitation of Additional Professional Education
Omsk
Web of Science Researcher ID: AAU-3847-2020,
SCOPUS ID: 660389166
Omsk
References
1. Chen TP, Yu HC, Lin WY, Chang YC. The role of microbiome in the pathogenesis of oral-gut-liver axis between periodontitis and nonalcoholic fatty liver disease. J Dent Sci. 2023; 18: 972–975. DOI: 10.1016/j.jds.2023.03.012
2. Wadia R. Periodontitis and systemic inflammation. Br Dent J. 2022;233(6):494. DOI: 10.1038/s41415-022-5038-4
3. Elghannam MT, Hassanien MH, Ameen YA. et al. Oral microbiome dysbiosis and gastrointestinal diseases: a narrative review. Egypt Liver J. 2024; 14: 32. DOI: 10.1186/s43066-024-00340-9
4. Kobayashi R, Ogawa Y, Hashizume-Takizawa T, Kurita-Ochiai T. Oral bacteria affect the gut microbiome and intestinal immunity. Pathog Dis. 2020; 78 (3): ftaa024. DOI: 10.1093/femspd/ftaa024.
5. Lei Y, Li S, He M. et al. Oral pathogenic bacteria and the oral-gut-liver axis: a new understanding of chronic liver diseases. Diagnostics (Basel). 2023; 13: 3324. DOI: 10.3390/diagnostics13213324
6. Zhu X, Huang H, Zhao L. PAMPs and DAMPs as the Bridge Between Periodontitis and Atherosclerosis: The Potential Therapeutic Targets. Front Cell Dev Biol. 2022; 10: 856118. DOI: 10.3389/fcell.2022.856118.
7. Herwald H, Egesten A.J. On PAMPs and DAMPs. Innate Immun. 2016; 8 (5): 427–428. DOI: 10.1159/000448437.
8. Olofsson LE, Bäckhed F. The Metabolic Role and Therapeutic Potential of the Microbiome. Endocr Rev. 2022; 43 (5): 907–926. DOI: 10.1210/endrev/bnac004
9. Benedé-Ubieto R, Cubero FJ, Nevzorova YA.Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD). Gut Microbes. 2024; 16 (1): 2331460. DOI: 10.1080/19490976.2024.2331460
10. Shen Y, Wu SD, Chen Y. et al. Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response. Gut Microbes. 2023; 15 (1): 2155018. DOI: 10.1080/19490976.2022.2155018
11. 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; 9: 822190. DOI: 10.3389/fmed.2022.822190
12. Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis. World J Gastroenterol. 2023; 29 (6): 967–996. DOI: 10.3748/wjg.v29.i6.967
13. Kuroe K, Furuta M, Takeuchi K, et al.: Association between periodontitis and fibrotic progression of nonalcoholic fatty liver among Japanese adults. J Clin Periodontol. 2021; 48: 368–377. DOI: 10.1111/jcpe.13415
14. Schwenger KJP, Sharma D, Ghorbani Y. et al. Links between gut microbiome, metabolome, clinical variables and non-alcoholic fatty liver disease severity in bariatric patients. Liver Int. 2024; 44 (5): 1176–1188. DOI: 10.1111/liv.15864
15. Dou J, Chen X, Zhang J. et al. P. Gingivalis induce macrophage polarization by regulating hepcidin expression in chronic apical periodontitis. Int Immunopharmacol. 2024; 142 (Pt A): 113139. DOI: 10.1016/j.intimp.2024.113139
16. Yuan K, Xu S, Liu G. et al. Porphyromonas gingivalis Promotes Oral Squamous Cell Carcinoma Progression by Modulating Autophagy. Oral Dis. 2025; 31 (2): 492–502. DOI: 10.1111/odi.15157
17. Vegda HS, Patel B, Girdhar GA. Et al. Role of Nonalcoholic Fatty Liver Disease in Periodontitis: A Bidirectional Relationship. Cureus. 2024; 16 (7): e63775. DOI: 10.7759/cureus.63775
18. Selvaraj EA, Mózes FE, Jayaswal AN, et al. Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: a systematic review and meta-analysis. J Hepatol. 2021; 75: 770–785. DOI: 10.1016/j.jhep.2021.04.044
19. Oka I, Shigeishi H, Ohta K. Co-Infection of Oral Candida albicans and Porphyromonas gingivalis Is Associated with Active Periodontitis in Middle-Aged and Older Japanese People. Medicina (Kaunas). 2022; 58 (6): 723. DOI: 10.3390/medicina58060723
20. Yamazaki K. Oral-gut axis as a novel biological mechanism linking periodontal disease and systemic diseases: a review. Jpn Dent Sci Rev. 2023; 59: 273–280. DOI: 10.1016/j.jdsr.2023.08.003
21. Yao C, Lan D, Li X. et al. Porphyromonas gingivalis is a risk factor for the development of nonalcoholic fatty liver disease via ferroptosis. Microbes Infect. 2023; 25: 105040. DOI: 10.1016/j.micinf.2022.105040
22. Rinčić G, Gaćina P, Virović Jukić L. et al. Association between periodontitis and liver disease. Acta Clin Croat. 2022; 60: 510–518. DOI: 10.20471/acc.2021.60.03.22
23. Kiryowa HM, Munabi IG, Buwembo W. et al. Periodontitis is associated with insulin resistance in adults living with diabetes mellitus in Uganda: a cross- sectional study. BMC Res Notes. 2023; 16: 217. DOI: 10.1186/s13104-023-06473-1
24. Pussinen PJ, Kopra E, Pietiäinen M. et al. Periodontitis and cardiometabolic disorders: the role of lipopolysaccharide and endotoxemia. Periodontol 2000. 2022; 89: 19–40. DOI: 10.1111/prd.12433
25. Xu T, Liu R, Zhu H. et al. The inhibition of LPS-induced oxidative stress and inflammatory responses is associated with the protective effect of (–)-epigallocatechin 3-gallate on bovine hepatocytes and murine liver. Antioxidants (Basel). 2022; 11: 914. DOI: 10.3390/antiox11050914
26. Geng X, Xia X, Liang Z. et al. Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis. Cell Mol Life Sci. 2024; 81 (1): 402. DOI: 10.1007/s00018-024-05424-8
27. Nakahara T, Hyogo H, Ono A. et al. Involvement of Porphyromonas gingivalis in the progression of nonalcoholic fatty liver disease. J Gastroenterol. 2018; 53: 269–280. DOI: 10.1007/s00535-017-1368-4
28. Kamata Y, Kessoku T, Shimizu T. et al. Periodontal treatment and usual care for nonalcoholic fatty liver disease: a multicenter, randomized controlled trial. Clin Transl Gastroenterol. 2022; 13: e00520. DOI: 10.14309/ctg.0000000000000520
29. Kobayashi T, Iwaki M, Nogami A. et al. Involvement of periodontal disease in the pathogenesis and exacerbation of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: a review. Nutrients. 2023; 15: 1269. DOI: 10.3390/nu15051269
30. 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
31. Takamura H, Yoshida K, Okamura H. et al. Porphyromonas gingivalis attenuates the insulin-induced phosphorylation and translocation of forkhead box protein O1 in human hepatocytes. Arch Oral Biol 2016; 69: 19–24. DOI: 10.1016/j.archoralbio.2016.05.010
32. Zaitsu Y, Iwatake M, Sato K, Tsukuba T. Lipid droplets affect elimination of Porphyromonas gingivalis in HepG2 cells by altering the autophagy-lysosome system. Microbes Infect 2016; 18: 565–571. DOI: 10.1016/j.micinf.2016.05.004
33. 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; 10: 4134. DOI: 10.1038/s41598-020-60904-8
34. Masi S, Gkranias N, Li K. et al. Association between short leukocyte telomere length, endotoxemia, and severe periodontitis in people with diabetes: a cross-sectional survey. Diabetes Care 2014; 37: 1140–1147. DOI: 10.2337/dc13-2106
35. Zbinden A, Bostanci N. Belibasakis GN. The novel species Streptococcus tigurinus and its association with oral infection. Virulence. 2015; 6(3):177–82. DOI:10.4161/21505594.2014.970472.
36. Raja M, Ummer F, Dhivakar CP Aggregatibacter actinomycetemcomitans-a tooth killer? J Clin Diagn Res. 2014; 8: ZE13–6. DOI:10.7860/JCDR/2014/9845.4766
37. Komazaki R, Katagiri S, Takahashi H. et al. Periodontal pathogenic bacteria, Aggregatibacter actinomycetemcomitans affect non-alcoholic fatty liver disease by altering gut microbiota and glucose metabolism. Sci Rep. 2017; 7: 13950. DOI: 10.1038/s41598-017-14260-9
38. Ozuna H, Snider I, Belibasakis GN. Aggregatibacter actinomycetemcomitans and Filifactor alocis: two exotoxin-producing oral pathogens. Front Oral Health. 2022; 3: 981343. DOI: 10.3389/froh.2022.981343
39. Tan X, Wang Y, Gong T. The interplay between oral microbiota, gut microbiota and systematic diseases. J Oral Microbiol. 2023;15: 2213112. DOI: 10.1080/20002297.2023.2213112
40. Vliex LM, Penders J, Nauta A. et al. The individual response to antibiotics and dietinsights into gut microbial resilience and host metabolism. Nat Rev Endocrinol. 2024; 20: 387–398. DOI: 10.1038/s41574-024-00966-0
41. Jeong SH, Nam Y, Jung H. et al. Interrupting oral infection of Porphyromonas gingivalis with anti-FimA antibody attenuates bacterial dissemination to the arthritic joint and improves experimental arthritis. Exp Mol Med 2018; 50: 1–2. DOI: 10.1038/s12276-018-0140-z
42. Cai J, Chen J, Guo H. et al. Recombinant fimbriae protein of Porphyromonas gingivalis induces an inflammatory response via the TLR4/NFκB signaling pathway in human peripheral blood mononuclear cells. Int J Mol Med 2019; 43: 1430–1440. DOI: 10.3892/ijmm.2019.4069
43. Dominy SS, Lynch C, Ermini F. Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with smallmolecule inhibitors. Sci Adv 2019; 5: eaau3333. DOI: 10.1126/sciadv.aau3333
44. Amini-Salehi E, Hassanipour S, Keivanlou MH. The impact of gut microbiome-targeted therapy on liver enzymes in patients with nonalcoholic fatty liver disease: an umbrella meta-analysis. Nutr Rev. 2024; 82 (6): 815–830. DOI: 10.1093/nutrit/nuad086
Review
For citations:
Akhmedov A.V. Non-alcoholic fatty liver disease and periodontitis – clinical and pathogenetic relationships. Medical alphabet. 2025;(13):12=15. (In Russ.) https://doi.org/10.33667/2078-5631-2025-13-12-15
Views:
42
Email this article 