Role of gut microbiota imbalance in alpha-synuclein induced microglia activation in patients with Parkinson's disease

doi:10.3760/cma.j.issn.1007-1245.2023.22.001

Abstract

Abstract:

More and more evidences show that gut microbiota is closely related to the development and progression of Parkinson's disease (PD). Recent studies have shown that gut microbiota can activate microglia in the brain by regulating alpha-synuclein (α-syn), aggravate neuroinflammation, and lead to dopamine neuron loss in patients with PD. In this paper, we review how the imbalance of gut microbiota leads to neuroinflammation through α-syn activation of microglia in the pathogenesis of PD.

Key words:

Parkinson's disease, Gut microbiota, Alpha-synuclein, Microglia, Progress

摘要：

越来越多证据表明，肠道菌群与帕金森病（PD）的发生和进展密切相关。最近研究发现，肠道菌群可以通过调控α-突触核蛋白（α-syn），激活脑内小胶质细胞，加重神经炎症，导致PD患者的多巴胺神经元丢失。本文就PD发病机制中肠道菌群失衡如何经α-syn激活小胶质细胞导致神经炎症进行综述。

关键词:

帕金森病, 肠道菌群, α-突触核蛋白, 小胶质细胞, 进展

Cai Jinfeng, Wang Hongcai, Ge Ruli.

Role of gut microbiota imbalance in alpha-synuclein induced microglia activation in patients with Parkinson's disease [J]. International Medicine and Health Guidance News, 2023, 29(22): 3153-3157.

蔡金凤王洪财葛汝丽.

肠道菌群失衡在帕金森病α-突触核蛋白诱导小胶质细胞活化中的作用 [J]. 国际医药卫生导报, 2023, 29(22): 3153-3157.

References

[1] Dogra N, Mani RJ, Katare DP. The gut-brain axis: two ways signaling in Parkinson's disease[J]. Cell Mol Neurobiol, 2022,42(2):315-332. DOI: 10.1007/s10571-021-01066-7.
[2] Dorsey ER, Bloem BR. The Parkinson pandemic-a call to action[J]. JAMA Neurol, 2018,75(1):9-10. DOI: 10.1001/jamaneurol.2017.3299.
[3] Nielsen SD, Pearson NM, Seidler K. The link between the gut microbiota and Parkinson's disease: a systematic mechanism review with focus on α-synuclein transport[J]. Brain Res, 2021,1769:147609. DOI: 10.1016/j.brainres.2021.147609.
[4] Abdel-Haq R, Schlachetzki JCM, Glass CK, et al. Microbiome-microglia connections via the gut-brain axis[J]. J Exp Med, 2019,216(1):41-59. DOI: 10.1084/jem.20180794.
[5] Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's Disease[J]. Cell, 2016,167(6):1469-1480.e12. DOI: 10.1016/j.cell.2016.11.018.
[6] Lv QK, Tao KX, Wang XB, et al. Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease[J]. Inflamm Res, 2023,72(3):443-462. DOI: 10.1007/s00011-022-01676-x.
[7] Huang Y, Liao J, Liu X, et al. Review: the role of intestinal dysbiosis in Parkinson's disease[J]. Front Cell Infect Microbiol, 2021,11:615075. DOI: 10.3389/fcimb.2021.615075.
[8] Sun MF, Zhu YL, Zhou ZL, et al. Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: gut microbiota, glial reaction and TLR4/TNF-α signaling pathway[J]. Brain Behav Immun, 2018,70:48-60. DOI: 10.1016/j.bbi.2018.02.005.
[9] Abdel-Haq R, Schlachetzki JCM, Boktor JC, et al. A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice[J]. Elife, 2022,11:e81453. DOI: 10.7554/eLife.81453.
[10] Zhu M, Liu X, Ye Y,et al. Gut Microbiota: a novel therapeutic target for Parkinson's disease[J]. Front Immunol, 2022,13:937555. DOI: 10.3389/fimmu.2022.937555.
[11] Zeng J, Wang X, Pan F, et al. The relationship between Parkinson's disease and gastrointestinal diseases[J]. Front Aging Neurosci, 2022,14:955919. DOI: 10.3389/fnagi.2022.955919.
[12] Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome[J]. Nature, 2011,473(7346):174-180. DOI: 10.1038/nature09944.
[13] Guo TT, Zhang Z, Sun Y, et al. Neuroprotective effects of sodium butyrate by restoring gut microbiota and inhibiting TLR4 signaling in mice with MPTP-induced Parkinson's disease[J]. Nutrients, 2023,15(4):930. DOI: 10.3390/nu15040930.
[14] Chen SJ, Chen CC, Liao HY, et al. Association of fecal and plasma levels of short-chain fatty acids with gut microbiota and clinical severity in patients with Parkinson disease[J]. Neurology, 2022,98(8):e848-e858. DOI: 10.1212/WNL.0000000000013225.
[15] Heiss CN, Mannerås-Holm L, Lee YS, et al. The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism[J]. Cell Rep, 2021,35(8):109163. DOI: 10.1016/j.celrep.2021.109163.
[16] Erny D, Hrabě de Angelis AL, Jaitin D,et al. Host microbiota constantly control maturation and function of microglia in the CNS[J]. Nat Neurosci, 2015,18(7):965-977. DOI: 10.1038/nn.4030.
[17] Lei Q, Wu T, Wu J, et al. Roles of α-synuclein in gastrointestinal microbiome dysbiosis-related Parkinson's disease progression (Review)[J]. Mol Med Rep, 2021,24(4):734. DOI: 10.3892/mmr.2021.12374.
[18] Manfready RA, Forsyth CB, Voigt RM, et al. Gut-brain communication in Parkinson's disease: enteroendocrine regulation by GLP-1[J]. Curr Neurol Neurosci Rep, 2022,22(7):335-342. DOI: 10.1007/s11910-022-01196-5.
[19] Lin CH, Chen CC, Chiang HL, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease[J]. J Neuroinflammation, 2019,16(1):129. DOI: 10.1186/s12974-019-1528-y.
[20] Kaur G, Behl T, Bungau S, et al. Dysregulation of the gut-brain axis, dysbiosis and influence of numerous factors on gut microbiota associated Parkinson's disease[J]. Curr Neuropharmacol, 2021,19(2):233-247. DOI: 10.2174/1570159X18666200606233050.
[21] Daniele SG, Béraud D, Davenport C, et al. Activation of MyD88-dependent TLR1/2 signaling by misfolded α-synuclein, a protein linked to neurodegenerative disorders[J]. Sci Signal, 2015,8(376):ra45. DOI: 10.1126/scisignal.2005965.
[22] Claudino Dos Santos JC, Lima MPP, Brito GAC, et al. Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis[J]. Ageing Res Rev, 2023,84:101812. DOI: 10.1016/j.arr.2022.101812.
[23] Zhong Z, Chen W, Gao H, et al. Fecal microbiota transplantation exerts a protective role in MPTP-induced Parkinson's disease via the TLR4/PI3K/AKT/NF-κB pathway stimulated by α-synuclein[J]. Neurochem Res, 2021,46(11):3050-3058. DOI: 10.1007/s11064-021-03411-0.
[24] Perez-Pardo P, Dodiya HB, Engen PA, et al. Role of TLR4 in the gut-brain axis in Parkinson's disease: a translational study from men to mice[J]. Gut, 2019,68(5):829-843. DOI: 10.1136/gutjnl-2018-316844.
[25] Campos-Acuña J, Elgueta D, Pacheco R. T-cell-driven inflammation as a mediator of the gut-brain axis involved in Parkinson's disease[J]. Front Immunol, 2019,10:239. DOI: 10.3389/fimmu.2019.00239.
[26] González H, Contreras F, Pacheco R. Regulation of the neurodegenerative process associated to Parkinson's Disease by CD4+ T-cells[J]. J Neuroimmune Pharmacol, 2015,10(4):561-575. DOI: 10.1007/s11481-015-9618-9.
[27] Zheng W, He R, Yan Z, et al. Regulation of immune-driven pathogenesis in Parkinson's disease by gut microbiota[J]. Brain Behav Immun, 2020,87:890-897. DOI: 10.1016/j.bbi.2020.01.009.
[28] Tan AH, Chong CW, Lim SY, et al. Gut microbial ecosystem in Parkinson disease: new clinicobiological insights from multi-omics[J]. Ann Neurol, 2021,89(3):546-559. DOI: 10.1002/ana.25982.
[29] Jamal S, Kumari A, Singh A, et al. Conformational ensembles of α-synuclein derived peptide with different osmolytes from temperature replica exchange sampling[J]. Front Neurosci, 2017,11:684. DOI: 10.3389/fnins.2017.00684.
[30] Zhao Z, Ning J, Bao XQ, et al. Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis[J]. Microbiome, 2021,9(1):226. DOI: 10.1186/s40168-021-01107-9.