北京大学学报(医学版) ›› 2025, Vol. 57 ›› Issue (5): 852-858. doi: 10.19723/j.issn.1671-167X.2025.05.007

• 工作综述 • 上一篇    下一篇

牙周炎与全身系统性疾病的思考与探索

曹沛, 栾庆先*()   

  1. 北京大学口腔医学院·口腔医院牙周科, 国家口腔医学中心, 国家口腔疾病临床医学研究中心, 口腔生物材料和数字诊疗装备国家工程研究中心, 北京 100081
  • 收稿日期:2025-07-31 出版日期:2025-10-18 发布日期:2025-08-27
  • 通讯作者: 栾庆先
  • 基金资助:
    2023YFC2506300(国家重点研发计划项目); 82370956(国家自然科学基金)

Periodontitis and systemic diseases: Thinking and explorations

Pei CAO, Qingxian LUAN*()   

  1. Department of Periodontology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
  • Received:2025-07-31 Online:2025-10-18 Published:2025-08-27
  • Contact: Qingxian LUAN
  • Supported by:
    the National Key Research and Development Program of China(国家重点研发计划项目); the National Natural Science Foundation of China(国家自然科学基金)

RICH HTML

  

摘要: 牙周炎已成为全球广泛流行的慢性炎症性疾病, 全球范围内约11%成年人患有重度牙周炎, 我国35岁以上人群牙周健康率不足10%, 中老年牙周炎患病率高达82.6%。在公共卫生视角下, 牙周炎不仅侵蚀口腔健康, 更与心血管疾病、糖尿病、认知障碍等慢性系统性疾病存在较强关联。大量队列研究和meta分析表明, 牙周炎患者发生心血管事件的风险显著增加, 糖尿病患者中牙周炎发展更快, 且具有双向因果关联。北京大学口腔医院牙周科长期致力于我国社区人群牙周炎与全身系统性疾病关系的研究, 本文系统回顾了我国社区人群牙周炎与心血管疾病、代谢综合征、认知障碍等系统性疾病的相关性, 通过动物学研究发现了实验性牙周炎可导致糖耐量异常、加重动脉粥样硬化进程, 并在深入探讨相应分子机制的基础上, 初步验证了线粒体DNA外溢、牙周致病菌入血可能是联系牙周炎与全身系统性疾病的桥梁。本文旨在深化关于牙周炎对全身影响的认知, 为我国口腔健康的公共卫生管理与慢性病预防提供科学指导。

关键词: 牙周炎, 全身系统性疾病, 心血管疾病, 糖尿病, 认知障碍, 线粒体DNA, 致病菌播散

Abstract: Periodontitis has become one of the most widespread chronic inflammatory diseases worldwide, affecting roughly 11% of the adult population. In China, periodontal health is notably poor, with less than 10% of individuals over the age of 35 maintaining periodontal health, while the prevalence of periodontitis in middle-aged and elderly populations reaches as high as 82.6%. From a public health perspective, periodontitis not only seriously compromises oral health but is also closely linked to multiple chronic systemic diseases, including cardiovascular disease, diabetes mellitus, and cognitive impairment. A substantial body of cohort studies and meta-analyses consistently demonstrate that patients with periodontitis are at a significantly increased risk of cardiovascular events. Moreover, periodontitis tends to progress more rapidly in individuals with diabetes, highlighting a bidirectional causal relationship between these two conditions. Our research team has maintained a long-term focus on elucidating the relationship between periodontitis and systemic diseases within Chinese community populations. In this review, we comprehensively summarize epidemiological findings on the associations between periodontitis and cardiovascular disease, metabolic syndrome, and cognitive decline, specifically drawing on data from Chinese cohorts. Complementing these observations, animal experiments provide evidence that experimental periodontitis can induce glucose intolerance and accelerate the development of atherosclerotic lesions. At the mechanistic level, we preliminarily validate that mitochondrial DNA efflux and the hematogenous spread of periodontal pathogens may act as biological conduits bridging local periodontal inflammation with systemic pathologies. We also address current challenges in the field, including difficulties in disentangling causal relationships due to confounding comorbidities like diabetes and cardiovascular diseases, which often coexist and influence each other. To advance understanding, there is an urgent need for well-designed longitudinal and interventional studies employing advanced causal inference methods. Ultimately, this work aims to deepen the current knowledge of periodontitis ' systemic effects and to support the development of evidence-based public health strategies for integrating oral health into chronic disease prevention efforts in China.

Key words: Periodontitis, Systemic diseases, Cardiovascular disease, Diabetes mellitus, Cognitive impairment, Mitochondrial DNA, Pathogen dissemination

中图分类号: 

  • R781.42
1
Nascimento GG, Alves-Costa S, Romandini M. Burden of severe periodontitis and edentulism in 2021, with projections up to 2050:The Global Burden of Disease 2021 study[J]. J Periodontal Res, 2024, 59(5): 823- 867.
2
Jiao J, Jing W, Si Y, et al. The prevalence and severity of periodontal disease in Mainland China: Data from the Fourth National Oral Health Survey (2015-2016)[J]. J Clin Periodontol, 2021, 48(2): 168- 179.

doi: 10.1111/jcpe.13396
3
Sanz M, Ceriello A, Buysschaert M, et al. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology[J]. J Clin Periodontol, 2018, 45(2): 138- 149.

doi: 10.1111/jcpe.12808
4
Herrera D, Molina A, Buhlin K, et al. Periodontal diseases and association with atherosclerotic disease[J]. Periodontol 2000, 2020, 83(1): 66- 89.

doi: 10.1111/prd.12302
5
Yang H, Cao P, Wang X, et al. Association of carotid intima-media thickness with periodontitis may depend on glycemic control[J]. Oral Dis, 2024, 30(4): 2609- 2616.

doi: 10.1111/odi.14622
6
Yu H, Qi LT, Liu LS, et al. Association of carotid intima-media thickness and atherosclerotic plaque with periodontal status[J]. J Dent Res, 2014, 93(8): 744- 751.

doi: 10.1177/0022034514538973
7
Liu J, Wang X, Zheng M, et al. Oxidative stress in human gingival fibroblasts from periodontitis versus healthy counterparts[J]. Oral Dis, 2023, 29(3): 1214- 1225.

doi: 10.1111/odi.14103
8
Cheng XY, Zou PH, Ma YM, et al. From gingiva to multiple organs in mice: The trace of Porphyromonas gingivalis via in vivo imaging[J]. J Dent Sci, 2025, 20(1): 292- 301.

doi: 10.1016/j.jds.2024.07.009
9
Di Cesare M, Perel P, Taylor S, et al. The heart of the world[J]. Global Heart, 2024, 19(1): 11.

doi: 10.5334/gh.1288
10
Center For Cardiovascular Diseases The Writing Committee Of The Report On Cardiovascular Health And Diseases In China. Report on cardiovascular health and diseases in China 2023:An updated summary[J]. Biomed Environ Sci, 2024, 37(9): 949- 992.
11
Tang K, Wu Y, Zheng Q, et al. Bibliometric research on analysis of links between periodontitis and cardiovascular diseases[J]. Front Cardiovasc Med, 2023, 10, 1255722.

doi: 10.3389/fcvm.2023.1255722
12
刘园, 栾庆先. 北京石景山社区中老年人群慢性牙周炎和颈动脉内膜中层厚度的相关性[J]. 北京大学学报(医学版), 2018, 50(2): 264- 270.

doi: 10.3969/j.issn.1671-167X.2018.02.011
13
Jönsson D, Orho-Melander M, Demmer RT, et al. Periodontal disease is associated with carotid plaque area: The Malmö Offspring Dental Study (MODS)[J]. J Intern Med, 2020, 287(3): 301- 309.

doi: 10.1111/joim.12998
14
Southerland JH, Moss K, Taylor GW, et al. Periodontitis and diabetes associations with measures of atherosclerosis and CHD[J]. Atherosclerosis, 2012, 222(1): 196- 201.

doi: 10.1016/j.atherosclerosis.2012.01.026
15
Neeland IJ, Lim S, Tchernof A, et al. Metabolic syndrome[J]. Nat Rev Dis Primers, 2024, 10(1): 77.

doi: 10.1038/s41572-024-00563-5
16
Xu X, Zeng J, Yang W, et al. Prevalence of metabolic syndrome among the adult population in western China and the association with socioeconomic and individual factors: Four cross-sectional studies[J]. BMJ Open, 2022, 12(4): e052457.

doi: 10.1136/bmjopen-2021-052457
17
于卓人, 刘丽笙, 栾庆先, 等. 北京石景山区老年人群牙周炎与代谢综合征的相关性探讨[J]. 北京大学学报(医学版), 2012, 44(4): 633- 638.
18
李蓬, 沙月琴, 和璐, 等. 北京某社区代谢综合征人群的牙周状况调查[J]. 实用口腔医学杂志, 2007, 23(3): 434- 438.
19
Li P, He L, Sha YQ, et al. Relationship of metabolic syndrome to chronic periodontitis[J]. J Periodontol, 2009, 80(4): 541- 549.

doi: 10.1902/jop.2009.080387
20
和璐, 李蓬, 沙月琴, 等. 代谢综合征患者与健康者唾液中肿瘤坏死因子α、白细胞介素1β水平比较[J]. 中华口腔医学杂志, 2010, 45(5): 269- 273.
21
Saito M, Shimazaki Y, Yoshii S, et al. Periodontitis and the incidence of metabolic syndrome: An 8-year longitudinal study of an adult Japanese cohort[J]. J Clin Periodontol, 2024, 51(1): 54- 62.

doi: 10.1111/jcpe.13881
22
Kotin J, Walther C, Wenzel U, et al. Association between periodontitis and metabolic syndrome in the Hamburg City Health Study[J]. J Periodontol, 2022, 93(8): 1150- 1160.

doi: 10.1002/JPER.21-0464
23
Stöhr J, Barbaresko J, Neuenschwander M, et al. Bidirectional association between periodontal disease and diabetes mellitus: A systematic review and meta-analysis of cohort studies[J]. Sci Rep, 2021, 11(1): 13686.

doi: 10.1038/s41598-021-93062-6
24
廖雁婷, 和璐, 李蓬, 等. 北京城区2型糖尿病患者牙周状况研究[J]. 中华糖尿病杂志, 2010, 2(4): 248- 252.
25
汤梓艳, 王晓霞, 杨泓, 等. 北京社区人群2型糖尿病血糖控制状态与牙周炎的相关性研究[J]. 北京口腔医学, 2023, 31(4): 274- 278.
26
张勇, 刘畅, 陈彬, 等. 糖尿病前期患者糖代谢异常与慢性牙周炎的相关性[J]. 北京大学学报(医学版), 2020, 52(1): 71- 76.

doi: 10.19723/j.issn.1671-167X.2020.01.011
27
Bai W, Chen P, Cai H, et al. Worldwide prevalence of mild cognitive impairment among community dwellers aged 50 years and older: A meta-analysis and systematic review of epidemiology studies[J]. Age Ageing, 2022, 51(8): afac173.
28
Jia L, Du Y, Chu L, et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: A cross-sectional study[J]. Lancet Public Health, 2020, 5(12): e661- e671.

doi: 10.1016/S2468-2667(20)30185-7
29
高巍, 刘力生, 王兴宇, 等. 北京社区老年人群缺牙数与认知障碍的关系[J]. 中华老年口腔医学杂志, 2015, 13(3): 164-167, 159.
30
Gao W, Wang X, Wang X, et al. Association of cognitive function with tooth loss and mitochondrial variation in adult subjects: A community-based study in Beijing, China[J]. Oral Dis, 2016, 22(7): 697- 702.

doi: 10.1111/odi.12529
31
Dibello V, Custodero C, Cavalcanti R, et al. Impact of periodontal disease on cognitive disorders, dementia, and depression: A systematic review and meta-analysis[J]. Geroscience, 2024, 46(5): 5133- 5169.

doi: 10.1007/s11357-024-01243-8
32
刘雪娇. 北京石景山社区中老年人群牙周炎与肾小球滤过率的相关性分析[D]. 北京: 北京大学医学部, 2021.
33
Grubbs V, Vittinghoff E, Taylor G, et al. The association of periodontal disease with kidney function decline: A longitudinal retrospective analysis of the MrOS dental study[J]. Nephrol Dial Transplant, 2016, 31(3): 466- 472.

doi: 10.1093/ndt/gfv312
34
Schütz JDS, de Azambuja CB, Cunha GR, et al. Association between severe periodontitis and chronic kidney disease severity in predialytic patients: A cross-sectional study[J]. Oral Dis, 2020, 26(2): 447- 456.

doi: 10.1111/odi.13236
35
Liu X, Wang F, Wang X, et al. Impact of body mass index and polycystic ovary syndrome (PCOS) subtypes on periodontal health in Chinese women with PCOS and periodontitis[J]. Gynecol Endocrinol, 2024, 40(1): 2405097.

doi: 10.1080/09513590.2024.2405097
36
耿祎然. 线粒体DNA在牙周炎与1型糖尿病双向关系中的潜在作用[D]. 北京: 北京大学, 2025.
37
Kang N, Zhang Y, Xue F, et al. Periodontitis induced by Porphyromonas gingivalis drives impaired glucose metabolism in mice[J]. Front Cell Infect Microbiol, 2022, 12, 998600.

doi: 10.3389/fcimb.2022.998600
38
Xuan Y, Shi Q, Liu GJ, et al. Porphyromonas gingivalis infection accelerates atherosclerosis mediated by oxidative stress and inflammatory responses in ApoE-/- mice[J]. Clin Lab, 2017, 63(10): 1627- 1637.
39
Deng Y, Xiao J, Ma L, et al. Mitochondrial dysfunction in periodontitis and associated systemic diseases: Implications for pathomechanisms and therapeutic strategies[J]. Int J Mol Sci, 2024, 25(2): 1024.

doi: 10.3390/ijms25021024
40
Liu J, Wang X, Xue F, et al. Abnormal mitochondrial structure and function are retained in gingival tissues and human gingival fibroblasts from patients with chronic periodontitis[J]. J Periodontal Res, 2022, 57(1): 94- 103.

doi: 10.1111/jre.12941
41
张孟钧, 栾庆先. 不同类型牙周炎患者唾液中8-OHdG含量的比较[J]. 口腔医学研究, 2017, 33(8): 898- 900.
42
Liu J, Wang Y, Shi Q, et al. Mitochondrial DNA efflux maintained in gingival fibroblasts of patients with periodontitis through ROS/mPTP pathway[J]. Oxid Med Cell Longev, 2022, 2022, 1000213.

doi: 10.1155/2022/1000213
43
Peres MA, MacPherson LMD, Weyant RJ, et al. Oral diseases: A global public health challenge[J]. Lancet, 2019, 394(10194): 249- 260.

doi: 10.1016/S0140-6736(19)31146-8
44
Shi Q, Luan Q, Wang X, et al. Correlation study on mtDNA polymorphisms as potential risk factors in aggressive periodontitis by NGS[J]. Oral Dis, 2020, 26(2): 401- 408.

doi: 10.1111/odi.13231
45
Wang X, Guo Y, Luan Q. Association of mitochondrial DNA displacement loop polymorphisms and aggressive periodontitis in a Chinese population: A pilot study[J]. Mitochondrial DNA, 2015, 26(3): 389- 395.

doi: 10.3109/19401736.2013.840589
46
Wang X, Luan Q, Chen Q, et al. Mitochondrial polymorphisms and dysfunction related to aggressive periodontitis: A pilot study[J]. Oral Dis, 2014, 20(5): 490- 498.

doi: 10.1111/odi.12163
47
闫睿, 栾庆先, 刘力笙, 等. 代谢综合征相关线粒体基因单核苷酸多态性与慢性牙周炎的关系[J]. 北京大学学报(医学版), 2014, 46(2): 264- 268.
48
Martins CC, Lockhart PB, Firmino RT, et al. Bacteremia following different oral procedures: Systematic review and meta-analysis[J]. Oral Dis, 2024, 30(3): 846- 854.

doi: 10.1111/odi.14531
49
Haraszthy VI, Zambon JJ, Trevisan M, et al. Identification of periodontal pathogens in atheromatous plaques[J]. J Periodontol, 2000, 71(10): 1554- 1560.
50
Xuan Y, Gao Y, Huang H, et al. Tanshinone IIA attenuates atherosclerosis in apolipoprotein E knockout mice infected with Porphyromonas gingivalis[J]. Inflammation, 2017, 40(5): 1631- 1642.
51
Huang X, Xie M, Wang Y, et al. Porphyromonas gingivalis aggravates atherosclerotic plaque instability by promoting lipid-laden macrophage necroptosis[J]. Signal Transduct Target Ther, 2025, 10, 171.

doi: 10.1038/s41392-025-02251-6
[1] 马保金, 李建华, 桑元华, 于洋, 仇吉川, 邵金龙, 李凯, 刘世岳, 杜密, 商玲玲, 葛少华. 基于微环境和干细胞调控的牙周组织再生关键技术的建立与应用[J]. 北京大学学报(医学版), 2025, 57(5): 841-846.
[2] 包振英, 王雅杰. 炎症指标和细胞因子联合检测在慢性牙周炎中的应用[J]. 北京大学学报(医学版), 2025, 57(4): 772-778.
[3] 陈子砚, 张晓悦, 顾亦梧, 常春. 2型糖尿病患者使用E-health管理疾病意愿与影响机制[J]. 北京大学学报(医学版), 2025, 57(3): 522-528.
[4] 石宇彤, 危伊萍, 胡文杰, 徐涛, 张浩筠. 罹患重度牙周炎下颌磨牙拔牙微翻瓣牙槽嵴保存效果评价[J]. 北京大学学报(医学版), 2025, 57(1): 33-41.
[5] 李敬谦, 朱子璐, 焦剑, 施捷. 隐形矫治重度牙周炎患者前牙区病理性移位患牙的临床疗效[J]. 北京大学学报(医学版), 2025, 57(1): 51-56.
[6] 毛雅晴, 陈震, 于尧, 章文博, 刘洋, 彭歆. 2型糖尿病对口腔鳞状细胞癌患者预后的影响[J]. 北京大学学报(医学版), 2024, 56(6): 1089-1096.
[7] 张培恒, 高莹, 吴红花, 张健, 张俊清. 暴发性1型糖尿病合并急性胰腺炎1例及文献回顾[J]. 北京大学学报(医学版), 2024, 56(5): 923-927.
[8] 李晋娜,许丽娜,李敏,宋怡,张静,贾龙斌. 急性脑梗死患者血清BDNF、IL-18、hs-CRP水平与血管性认知障碍的相关性[J]. 北京大学学报(医学版), 2024, 56(4): 708-714.
[9] 林郁婷,王华丽,田宇,巩俐彤,常春. 北京市老年人认知功能的影响因素[J]. 北京大学学报(医学版), 2024, 56(3): 456-461.
[10] 胡玉如,刘娟,李文静,赵亦兵,李启强,路瑞芳,孟焕新. Ⅲ期或Ⅳ期牙周炎患者龈沟液中有机酸浓度与牙周炎的关系[J]. 北京大学学报(医学版), 2024, 56(2): 332-337.
[11] 马雨佳,卢燃藜,周泽宸,李晓怡,闫泽玉,武轶群,陈大方. 基于两样本孟德尔随机化的失眠与2型糖尿病关联研究[J]. 北京大学学报(医学版), 2024, 56(1): 174-178.
[12] 张晗,秦亦瑄,韦帝远,韩劼. 牙周炎患者种植修复维护治疗依从性的影响因素[J]. 北京大学学报(医学版), 2024, 56(1): 39-44.
[13] 殳畅,韩烨,孙雨哲,杨再目,侯建霞. Ⅲ期牙周炎患者牙周基础治疗前后炎症性贫血相关指标的变化[J]. 北京大学学报(医学版), 2024, 56(1): 45-50.
[14] 陈楚云,孙蓬飞,赵静,贾佳,范芳芳,王春燕,李建平,姜一梦,霍勇,张岩. 北京社区人群促红细胞生成素相关因素及其与10年心血管疾病风险的关系[J]. 北京大学学报(医学版), 2023, 55(6): 1068-1073.
[15] 鲍雷,蔡夏夏,张明远,任磊磊. 维生素D3对2型糖尿病小鼠轻度认知障碍的改善作用及机制研究[J]. 北京大学学报(医学版), 2023, 55(4): 587-592.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!