国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (1): 102-108.doi: 10.7518/gjkq.2020012

• 综述 • 上一篇    下一篇

口腔微生物种群与阿尔茨海默病相关发病机制的研究进展

张明爽1,2,巴特2,王文标1,2,()   

  1. 1. 潍坊医学院口腔医学院 潍坊 261000
    2. 航空总医院口腔外科 北京 100020
  • 收稿日期:2019-04-12 修回日期:2019-08-01 出版日期:2020-01-01 发布日期:2020-01-01
  • 通讯作者: 王文标
  • 作者简介:张明爽,医师,硕士,Email: 675216088@qq.com
  • 基金资助:
    北京市朝阳区科技计划项目(CYSF1724)

Research progress on oral microorganisms affect Alzheimer’s disease

Zhang Mingshuang1,2,Ba Te2,Wang Wenbiao1,2,()   

  1. 1. College of Stomatology, Weifang Medical University, Weifang 261000, China
    2. Dept. of Oral Surgery, Aviation General Hospital, Beijing 100020, China
  • Received:2019-04-12 Revised:2019-08-01 Online:2020-01-01 Published:2020-01-01
  • Contact: Wenbiao Wang
  • Supported by:
    This study was supported by Program for Science and Technology Projects in Beijing Chaoyang District(CYSF1724)

摘要:

口腔微生物种群如细菌、真菌等能引起龋病和牙周病等一系列口腔疾病,其代谢产物能进入血液,引起系统性炎症。阿尔茨海默病(AD)是一种中枢神经系统变性疾病,是痴呆症最常见的形式。据世界卫生组织统计,AD占痴呆症病例的60%~70%,并且其发病率仍在逐年攀升,给全球社会经济造成沉重负担。AD的临床病理特征为β-淀粉样蛋白沉积(Aβ)形成细胞外老年斑、tau蛋白过度磷酸化引起神经原纤维缠结,以及神经元丢失伴胶质细胞增生等。但目前为止,AD的病因及发病机制尚未阐明。近期研究发现,引起慢性牙周炎的微生物种群是Aβ沉积和AD发病的重大风险因素。因此,本文围绕口腔微生物种群与AD潜在的发病机制进行综述。

关键词: 阿尔茨海默病, 口腔微生物种群, 牙龈卟啉单胞菌, β-淀粉样蛋白

Abstract:

Oral microorganisms such as bacteria and fungi can cause a series of oral diseases, including caries and periodontitis. Some oral pathogens can cause systemic inflammation by secreting metabolites into the blood. Alzheimer’s disease (AD), a neurodegenerative disease, is the most common form of dementia. According to the World Health Organization, AD accounts for 60%-70% of dementia cases. With its morbidity increasing annually, AD has become one of the world’s most difficult problems. Amyloid β-protein (Aβ) deposition, hyperphosphorylation of tau protein, and loss of neurons with glial cell proliferation have been found in the brains of patients with AD. However, the pathogenesis of AD has not been elucidated. Recent studies reported that some oral microorganisms causing chronic periodontitis had become a significant risk factor for Aβ deposition and AD. Therefore, this article reviews the relationship between oral microorganisms and potential pathogenesis of AD.

Key words: Alzheimer’s disease, oral microorganism, Porphyromonas gingivalis, amyloid β-protein

中图分类号: 

  • R37
6 参考文献
[1] Fung TC, Olson CA, Hsiao EY . Interactions between the microbiota, immune and nervous systems in health and disease[J]. Nat Neurosci, 2017,20(2):145-155.
[2] Tcw J . Human iPSC application in Alzheimer’s disease and Tau-related neurodegenerative diseases[J]. Neurosci Lett, 2019,699:31-40.
[3] Mysak J, Podzimek S, Sommerova P , et al. Porphyro-monas gingivalis: major periodontopathic pathogen overview[J]. J Immunol Res, 2014,2014:476068.
[4] Jia JP, Wei CB, Chen SQ , et al. The cost of Alzheimer’s
disease in China and re-estimation of costs worldwid [J]. Alzheimers Dement, 2018,14(4):483-491.
[5] Olsen I, Yilmaz Ö . Possible role of Porphyromonas gingivalis in orodigestive cancers[J]. J Oral Micro-biol, 2019,11(1):1563410.
[6] Karpiński TM . Role of oral microbiota in cancer de- velopment[J]. Microorganisms, 2019,7(1):E20.
[7] Cai J, Chen JM, Guo HX , et al. Recombinant fim-briae protein of Porphyromonas gingivalis induces an inflammatory response via the TLR4/NF-κB signaling pathway in human peripheral blood mo-nonuclear cells[J]. Int J Mol Med, 2019,43(3):1430-1440.
[8] Ohtsu A, Takeuchi Y, Katagiri S , et al. Influence of Porphyromonas gingivalis in gut microbiota of streptozotocin-induced diabetic mice[J]. Oral Dis, 2019,25(3):868-880.
[9] Ayala-Herrera JL, Abud-Mendoza C, Gonzalez-Amaro RF , et al. Distribution of Porphyromonas gingivalis fimA genotypes in patients affected by rheumatoid arthritis and periodontitis[J]. Acta Odontol Scand, 2018,76(7):520-524.
[10] Bale BF, Doneen AL, Vigerust DJ . High-risk perio-dontal pathogens contribute to the pathogenesis of atherosclerosis[J]. Postgrad Med J, 2017,93(1098):215-220.
[11] Moazzam AA, Rajagopal SM, Sedghizadeh PP , et al. Intracranial bacterial infections of oral origin[J]. J Clin Neurosci, 2015,22(5):800-806.
[12] Bredesen DE . Metabolic profiling distinguishes three subtypes of Alzheimer’s disease[J]. Aging (Albany NY), 2015,7(8):595-600.
[13] Holmer J, Eriksdotter M, Schultzberg M , et al. Asso-ciation between periodontitis and risk of Alzheimer’s disease, mild cognitive impairment and subjective cognitive decline: a case-control study[J]. J Clin Pe-riodontol, 2018,45(11):1287-1298.
[14] Williams TL, Day IJ, Serpell LC . The effect of Alzheimer’s Aβ aggregation state on the permeation of biomimetic lipid vesicles[J]. Langmuir, 2010,26(22):17260-17268.
[15] Singhrao SK, Olsen I . Are Porphyromonas gingivalis outer membrane vesicles microbullets for sporadic Alzheimer’s disease manifestation[J]. J Alzheimers Dis Rep, 2018,2(1):219-228.
[16] Teixeira FB, Saito MT, Matheus FC , et al. Perio-dontitis and Alzheimer’s disease: a possible comor-bidity between oral chronic inflammatory condition and neuroinflammation[J]. Front Aging Neurosci, 2017,9:327.
[17] Koren O, Spor A, Felin J , et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis[J]. Proc Natl Acad Sci U S A, 2011,108(Suppl 1):4592-4598.
[18] 唐智群, 梁丹, 成杪莹 , 等. 牙周炎与阿尔兹海默症相关性研究进展[J]. 中国实用口腔科杂志, 2018,11(1):52-56.
Tang ZQ, Liang D, Cheng MY , et al. Research pro-gress in the association between Alzheimer’s disease and periodontitis[J]. Chin J Pract Stomatol, 2018,11(1):52-56.
[19] Singhrao SK, Harding A, Poole S , et al. Porphyromonas gingivalis periodontal infection and its putative links with Alzheimer’s disease[J]. Mediat Inflamm, 2015,2015:1-10.
[20] Roselaar SE, Daugherty A . Apolipoprotein E-deficient mice have impaired innate immune responses to Lis- teria monocytogenes in vivo[J]. J Lipid Res, 1998,39(9):1740-1743.
[21] de Bont N, Netea MG, Demacker PN , et al. Apolipo-protein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection[J]. J Lipid Res, 1999,40(4):680-685.
[22] Noble JM, Scarmeas N, Celenti RS , et al. Serum IgG antibody levels to periodontal microbiota are associated with incident Alzheimer disease[J]. PLoS One, 2014,9(12):e114959.
[23] Singhrao SK, Chukkapalli S, Poole S , et al. Chronic Porphyromonas gingivalis infection accelerates the occurrence of age-related granules in ApoE -/- mice brains[J]. J Oral Microbiol, 2017,9(1):1270602.
[24] Ishida N, Ishihara Y, Ishida K , et al. Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice[J]. Npj Aging Mech Dis, 2017,3:15.
[25] Gui MJ, Dashper SG, Slakeski N , et al. Spheres of influence: Porphyromonas gingivalis outer mem-brane vesicles[J]. Mol Oral Microbiol, 2016,31(5):365-378.
[26] Kamer AR, Pirraglia E, Tsui W , et al. Periodontal disease associates with higher brain amyloid load in normal elderly[J]. Neurobiol Aging, 2015,36(2):627-633.
[27] Ide M, Harris M, Stevens A , et al. Periodontitis and cognitive decline in Alzheimer’s disease[J]. PLoS One, 2016,11(3):e0151081.
[28] Miklossy J . Historic evidence to support a causal relationship between spirochetal infections and Alzheimer’s disease[J]. Front Aging Neurosci, 2015,7:46.
[29] Maheshwari P, Eslick GD . Bacterial infection and Al-zheimer’s disease: a meta-analysis[J]. J Alzheimers Dis, 2015,43(3):957-966.
[30] Riviere GR, Riviere KH, Smith KS . Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer’s disease[J]. Oral Microbiol Immunol, 2002,17(2):113-118.
[31] Sakai K, Fukuda T, Iwadate K , et al. A fatal fall asso-ciated with undiagnosed parenchymatous neurosy-philis[J]. Am J Forensic Med Pathol, 2014,35(1):4-7.
[32] Song J, Lee JE . MiR-155 is involved in Alzheimer’s disease by regulating T lymphocyte function[J]. Front Aging Neurosci, 2015,7:61.
[33] Miklossy J . Chronic inflammation and amyloidogenesis in Alzheimer’s disease: role of Spirochetes[J]. J Alzheimers Dis, 2008,13(4):381-391.
[34] Lukehart SA ,Hook EW 3rd,Baker-Zander SA, et al.Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment[J].Ann Intern Med, 1988,109(11):855-862.
[35] 陈渠奕, 林路得, 斯灵 , 等. 口腔微生物群和人体健康[J]. 中国微生态学杂志, 2017,29(10):1219-1224.
Chen QY, Lin LD, Si L , et al. Oral microbiota and human health[J]. Chin J Microecol, 2017,29(10):1219-1224.
[36] Wang QQ, Zhang CF, Chu CH , et al. Prevalence of Enterococcus faecalis in saliva and filled root canals of teeth associated with apical periodontitis[J]. Int J Oral Sci, 2012,4(1):19-23.
[37] Underly R, Song MS, Dunbar GL , et al. Expression of Alzheimer-type neurofibrillary epitopes in primary rat cortical neurons following infection with Ente-rococcus faecalis[J]. Front Aging Neurosci, 2015,7:259.
[38] Letenneur L, Pérès K, Fleury H , et al. Seropositivity to herpes simplex virus antibodies and risk of Al-zheimer’s disease: a population-based cohort study[J]. PLoS One, 2008,3(11):e3637.
[39] Itzhaki RF, Cosby SL, Wozniak MA . Herpes simplex virus type 1 and Alzheimer’s disease: the autophagy connection[J]. J Neurovirol, 2008,14(1):1-4.
[40] Meer-Scherrer L, Chang Loa C, Adelson ME , et al. Lyme disease associated with Alzheimer’s disease[J]. Curr Microbiol, 2006,52(4):330-332.
[41] Woodbury ME, Freilich RW, Cheng CJ , et al. Mir- 155 is essential for inflammation-induced hippo-campal neurogenic dysfunction[J]. J Neurosci, 2015,35(26):9764-9781.
[42] Eimer WA, Vijaya Kumar DK, Navalpur Shanmugam NK , et al. Alzheimer’s disease-associated β-amyloid is rapidly seeded by herpesviridae to protect against brain infection[J]. Neuron, 2018, 99(1): 56-63.e3.
[43] Lewis RE . Overview of the changing epidemiology of candidemia[J]. Curr Med Res Opin, 2009,25(7):1732-1740.
[44] Kumar J, Sharma R, Sharma M , et al. Presence of Candida albicans in root canals of teeth with apical periodontitis and evaluation of their possible role in failure of endodontic treatment[J]. J Int Oral Health, 2015,7(2):42-45.
[45] Alonso R, Pisa D, Marina AI , et al. Fungal infection in patients with Alzheimer’s disease[J]. J Alzheimers Dis, 2014,41(1):301-311.
[46] Alonso R, Pisa D, Rábano A , et al. Alzheimer’s disease and disseminated mycoses[J]. Eur J Clin Microbiol Infect Dis, 2014,33(7):1125-1132.
[47] Pisa D, Alonso R, Juarranz A , et al. Direct visualiza-tion of fungal infection in brains from patients with Alzheimer’s disease[J]. J Alzheimers Dis, 2015,43(2):613-624.
[48] Ranjan R, Abhinay A, Mishra M . Can oral microbial infections be a risk factor for neurodegeneration? A review of the literature[J]. Neurol India, 2018,66(2):344-351.
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