Gut Microbiota and Metabolites of α-synuclein Transgenic Monkey Models with Early Stage of Parkinson's Disease

Overview

Journal NPJ Biofilms Microbiomes

Date 2021 Sep 3

PMID 34475403

Citations 20

Authors

Yaping Yan

Shuchao Ren

Yanchao Duan

Chenyu Lu

Yuyu Niu

Zhengbo Wang

Briauna Inglis

Weizhi Ji

Yun Zheng

Wei Si

Affiliations

Soon will be listed here.

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. However, it is unclear whether microbiota and metabolites have demonstrated changes at early PD due to the difficulties in diagnosis and identification of early PD in clinical practice. In a previous study, we generated A53T transgenic monkeys with early Parkinson's symptoms, including anxiety and cognitive impairment. Here we analyzed the gut microbiota by metagenomic sequencing and metabolites by targeted gas chromatography. The gut microbiota analysis showed that the A53T monkeys have higher degree of diversity in gut microbiota with significantly elevated Sybergistetes, Akkermansia, and Eggerthella lenta compared with control monkeys. Prevotella significantly decreased in A53T transgenic monkeys. Glyceric acid, L-Aspartic acid, and p-Hydroxyphenylacetic acid were significantly elevated, whereas Myristic acid and 3-Methylindole were significantly decreased in A53T monkeys. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (KO0131) and the oxidative phosphorylation reaction (KO2147) were significantly increased in metabolic pathways of A53T monkeys. Our study suggested that the transgenic A53T and α-syn aggregation may affect the intestine microbiota and metabolites of rhesus monkeys, and the identified five compositional different metabolites that are mainly associated with mitochondrial dysfunction may be related to the pathogenesis of PD.

Citing Articles

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References

Ganapathy V, Thangaraju M, Prasad P, Martin P, Singh N . Transporters and receptors for short-chain fatty acids as the molecular link between colonic bacteria and the host. Curr Opin Pharmacol. 2013; 13(6):869-74. DOI: 10.1016/j.coph.2013.08.006. View

Unger M, Spiegel J, Dillmann K, Grundmann D, Philippeit H, Burmann J . Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord. 2016; 32:66-72. DOI: 10.1016/j.parkreldis.2016.08.019. View

Nakajima H, Amano W, Fujita A, Fukuhara A, Azuma Y, Hata F . The active site cysteine of the proapoptotic protein glyceraldehyde-3-phosphate dehydrogenase is essential in oxidative stress-induced aggregation and cell death. J Biol Chem. 2007; 282(36):26562-74. DOI: 10.1074/jbc.M704199200. View

Bueler H . Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson's disease. Exp Neurol. 2009; 218(2):235-46. DOI: 10.1016/j.expneurol.2009.03.006. View

Dodd D, Spitzer M, Van Treuren W, Merrill B, Hryckowian A, Higginbottom S . A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature. 2017; 551(7682):648-652. PMC: 5850949. DOI: 10.1038/nature24661. View

Yang X, Qian Y, Xu S, Song Y, Xiao Q . Longitudinal Analysis of Fecal Microbiome and Pathologic Processes in a Rotenone Induced Mice Model of Parkinson's Disease. Front Aging Neurosci. 2018; 9:441. PMC: 5766661. DOI: 10.3389/fnagi.2017.00441. View

Usuki T, Sakai H, Shionoya T, Sato N, Sakane F . Expression and localization of type II diacylglycerol kinase isozymes δ and η in the developing mouse brain. J Histochem Cytochem. 2014; 63(1):57-68. PMC: 4395997. DOI: 10.1369/0022155414559130. View

Blaylock R . Parkinson's disease: Microglial/macrophage-induced immunoexcitotoxicity as a central mechanism of neurodegeneration. Surg Neurol Int. 2017; 8:65. PMC: 5421223. DOI: 10.4103/sni.sni_441_16. View

Usuki T, Takato T, Lu Q, Sakai H, Bando K, Kiyonari H . Behavioral and pharmacological phenotypes of brain-specific diacylglycerol kinase δ-knockout mice. Brain Res. 2016; 1648(Pt A):193-201. DOI: 10.1016/j.brainres.2016.07.017. View

10.

Youngblut N, Reischer G, Walters W, Schuster N, Walzer C, Stalder G . Host diet and evolutionary history explain different aspects of gut microbiome diversity among vertebrate clades. Nat Commun. 2019; 10(1):2200. PMC: 6522487. DOI: 10.1038/s41467-019-10191-3. View

11.

Galan J, Collmer A . Type III secretion machines: bacterial devices for protein delivery into host cells. Science. 1999; 284(5418):1322-8. DOI: 10.1126/science.284.5418.1322. View

12.

Vidal-Martinez G, Chin B, Camarillo C, Herrera G, Yang B, Sarosiek I . A Pilot Microbiota Study in Parkinson's Disease Patients versus Control Subjects, and Effects of FTY720 and FTY720-Mitoxy Therapies in Parkinsonian and Multiple System Atrophy Mouse Models. J Parkinsons Dis. 2019; 10(1):185-192. PMC: 7029363. DOI: 10.3233/JPD-191693. View

13.

Hertel J, Harms A, Heinken A, Baldini F, Thinnes C, Glaab E . Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson's Disease. Cell Rep. 2019; 29(7):1767-1777.e8. PMC: 6856723. DOI: 10.1016/j.celrep.2019.10.035. View

14.

Sharon G, Cruz N, Kang D, Gandal M, Wang B, Kim Y . Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell. 2019; 177(6):1600-1618.e17. PMC: 6993574. DOI: 10.1016/j.cell.2019.05.004. View

15.

Rocha E, De Miranda B, Sanders L . Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease. Neurobiol Dis. 2017; 109(Pt B):249-257. DOI: 10.1016/j.nbd.2017.04.004. View

16.

Kim S, Kwon S, Kam T, Panicker N, Karuppagounder S, Lee S . Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019; 103(4):627-641.e7. PMC: 6706297. DOI: 10.1016/j.neuron.2019.05.035. View

17.

de la Fuente-Nunez C, Meneguetti B, Franco O, Lu T . Neuromicrobiology: How Microbes Influence the Brain. ACS Chem Neurosci. 2017; 9(2):141-150. DOI: 10.1021/acschemneuro.7b00373. View

18.

Bloem B, Okun M, Klein C . Parkinson's disease. Lancet. 2021; 397(10291):2284-2303. DOI: 10.1016/S0140-6736(21)00218-X. View

19.

Maini Rekdal V, Bess E, Bisanz J, Turnbaugh P, Balskus E . Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science. 2019; 364(6445). PMC: 7745125. DOI: 10.1126/science.aau6323. View

20.

Belarbi K, Cuvelier E, Destee A, Gressier B, Chartier-Harlin M . NADPH oxidases in Parkinson's disease: a systematic review. Mol Neurodegener. 2017; 12(1):84. PMC: 5683583. DOI: 10.1186/s13024-017-0225-5. View