Relationship between Oral Microbiota and Alzheimer's Disease

LI Yu-chen, LIU Yuan, CHEN Feng, CHU Ming, CHEN Xiao-chi

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease. In an aging society, the high prevalence of AD and the low quality of life of AD patients create serious problems for individuals, families and the society. However, the etiology and pathogenesis of AD are still not fully understood. Age, genetics, environment and other factors are all relevant to AD, and treatment has not achieved satisfactory results. Recent studies have found that oral dysbiosis is closely related to the pathogenesis of AD, and that oral bacterial infection may be one of the causes of AD. Oral cavity is the largest microbial ecosystem of human body, and its homeostasis is critical to health. Bacterial infections caused by oral dysbiosis can directly and indirectly induce the metabolic imbalance of amyloid β-protein (Aβ) in the brain and the hyperphosphorylation of Tau protein. Then, the precipitation forms senile plaques and neurofibrillary tangles (NFTs) that damage neurons. Based on the latest research findings, we herein discussed the correlation between oral microbiota and the pathogenesis of AD and the mechanisms involved, as well as the pathogenic mechanism of main oral bacteria. In addition, we explored the potential application prospects of oral microbiota-targeted therapy.

 

Keywords: Alzheimer's disease,/ Oral microbiota, Neuroinflammation, Porphyromonas gingivalis

 

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References


SILVA M V F， LOURES C M G， ALVES L C V， et al. Alzheimer’s disease: Risk factors and potentially protective measures. J Biomed Sci， 2019，26(1): 33.

WADE W G. The oral microbiome in health and disease. Pharmacol Res， 2013，69(1): 137–143.

GAO L， XU T， HUANG G， et al. Oral microbiomes: More and more importance in oral cavity and whole body. Protein Cell，2018，9(5): 488–500.

WANG X， SUN G， FENG T， et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res， 2019，29(10): 787–803.

LIU X X， JIAO B， LIAO X X， et al. Analysis of salivary microbiome in patients with Alzheimer’s disease. J Alzheimers Dis，2019，72(2): 633–640. TAKEUCHI K， OHARA T， FURUTA M， et al. Tooth loss and risk of Dementia in the community: The hisayama study. J Am Geriatr Soc， 2017， 65(5): e95-e100[2021-09-23].

EMERY D C， SHOEMARK D K， BATSTONE T E， et al. 16S rRNA next generation sequencing analysis shows bacteria in Alzheimer’s post-mortem brain. Front Aging Neurosci， 2017， 9: 195[2021-09-22]. https://doi.org/10.3389/fnagi.2017.00195.

RIVIERE G R， RIVIERE K H， SMITH K S， et al. Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer’s disease. Oral Microbiol Immunol，2002， 17(2): 113–118.

DOULBERIS M， KOTRONIS G， THOMANN R， et al. Review: Impact of Helicobacter pylori on Alzheimer’s disease: What do we know so far?Helicobacter， 2018， 23(1): 10.1111/hel. 12454[2021-09-24]. https://doi. org/10.1111/hel.12454.

POOLE S， SINGHRAO S K， KESAVALU L， et al. Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer’s disease brain tissue. J Alzheimers Dis，2013，36(4): 665–677.

POOLE S， SINGHRAO S K， CHUKKAPALLI S， et al. Active invasion of Porphyromonas gingivalis and infection-induced complement activation in ApoE-/- mice brains. J Alzheimers Dis，2015，43(1): 67–80.

BOWMAN G L， DAYON L， KIRKLAND R， et al. Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults. Alzheimers Dement，2018，14(12): 1640–1650.

GIL-MONTOYA J A， BARRIOS R， SANTANA S， et al. Association between periodontitis and amyloid β peptide in elderly people with and without cognitive impairment. J Periodontol，2017，88(10): 1051–1058. HARDING A， GONDER U， ROBINSON S J， et al. Exploring the association between Alzheimer’s disease， oral health， microbial endocrinology and nutrition. Front Aging Neurosci， 2017， 9: 398[2021-09-24]. https://doi.org/10.3389/fnagi.2017.00398.

BANKS W A， FARR S A， MORLEY J E. Entry of blood-borne cytokines into the central nervous system: Effects on cognitive processes. Neuroimmunomodulation，2002，10(6): 319–327.

SUNDAR S， BATTISTONI C， MCNULTY R， et al. An agent-based model to investigate microbial initiation of Alzheimer’s via the olfactory system. Theor Biol Med Model，2020，17(1): 5.

SUREDA A， DAGLIA M， ARGÜELLES CASTILLA S， et al. Oral microbiota and Alzheimer’s disease: Do all roads lead to Rome?Pharmacol Res， 2020， 151: 104582[2021-09-25]. https://doi.org/10.1016/j.phrs.2019.104582.

TANAKA M， TOLDI J， VÉCSEI L. Exploring the etiological links behind neurodegenerative diseases: Inflammatory cytokines and bioactive kynurenines. Int J Mol Sci，2020，21(7): 2431.

ZHANG J， YU C， ZHANG X， et al. Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice. J Neuroinflammation，2018，15(1): 37.

SMITH D R， PRICE J E， BURBY P E， et al. The production of curli amyloid fibers is deeply integrated into the biology of Escherichia coli. Biomolecules，2017，7(4): 75.

LUKIW W J. Gastrointestinal (GI) tract microbiome-derived neurotoxins-potent neuro-inflammatory signals from the GI tract via the systemic circulation into the brain. Front Cell Infect Microbiol， 2020， 10: 22[2021-10-15]. https://doi.org/10.3389/fcimb.2020.00022.

DIOGUARDI M， CRINCOLI V， LAINO L， et al. The role of periodontitis and periodontal bacteria in the onset and progression of Alzheimer’s disease: A systematic review. J Clin Med，2020，9(2): 495.

MONTAGNE A， ZHAO Z， ZLOKOVIC B V. Alzheimer’s disease: A matter of blood-brain barrier dysfunction? J Exp Med，2017，214(11): 3151–3169.

UMEDA T， ONO K， SAKAI A， et al. Rifampicin is a candidate preventive medicine against amyloid-β and tau oligomers. Brain，2016， 139(Pt 5): 1568–1586.

WANG Y， GUAN PP， YU X， et al. COX-2 metabolic products, the prostaglandin I2 and F2α, mediate the effects of TNF-α and Zn2+ in stimulating the phosphorylation of Tau. Oncotarget，2017，8(59): 99296–99311.

POLIAKOVA T， LEVIN O， ARABLINSKIY A， et al. Cerebral microbleeds in early Alzheimer’s disease. J Neurol，2016，263(10): 1961–1968.


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