Unraveling the Nexus: Parkinson’s Disease, Alpha-synuclein, Desulfovibrio, and the Gut Microbiome

Year : 2024 | Volume : 02 | Issue : 01 | Page : 18 28
    By

    Fatima Abdul Azeez,

  1. Student, Department of biotechnology, Mar Athanasius College, Kothamangalam,, Kerala, India

Abstract

Parkinson’s disease (PD) is now recognized as a chronic condition which is once considered a highly intricate disorder involving the central, autonomic, and enteric nervous systems. The prevailing perspective attributes the disease by the formation of Lewy bodies, primarily triggered by the misfolding of α-Synuclein, leading to the demise of dopaminergic neurons in the substantia nigra. Constipation, one of the most common non-motor symptoms in PD patients, is believed to be influenced by the composition of gut bacteria. The gastrointestinal tract acts as a significant point of entry through the vagus nerve for potentially harmful microorganisms that can initiate the pathological process of PD. The vagus nerve is proposed to play a role in transmitting signals leading to the over-expression and accumulation of α-Synuclein in the brain. In a study, it was noted that individuals with PD displayed an elevated occurrence of bacteria belonging to the Desulfovibrionaceae family. Desulfovibrio (DSV) are sulfate-reducing bacteria (SRB) that are established as commensal bacteria in the human gastrointestinal tract. Desulfovibrio releases certain metabolites that trigger the aggregation of alpha-synuclein leading to play a role in the pathogenesis of PD. The presence of DSV can lead to a decline in bacterial metabolites, which plays a crucial role in gut health and contributes to the effects observed in individuals with PD. This review consolidates current knowledge on the connection between DSV and PD, emphasizing the role of the gut environment. We address the possibilities that could be considered for reducing the α-Synuclein aggregation in this study by emphasizing Desulfovibrio.

Keywords: Parkinson’s disease, Neurodegenerative Disease, Desulfovibrio, α-Synuclein, Cellular toxicity.

[This article belongs to International Journal of Cell Biology and Cellular Functions ]

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How to cite this article:
Fatima Abdul Azeez. Unraveling the Nexus: Parkinson’s Disease, Alpha-synuclein, Desulfovibrio, and the Gut Microbiome. International Journal of Cell Biology and Cellular Functions. 2024; 02(01):18-28.
How to cite this URL:
Fatima Abdul Azeez. Unraveling the Nexus: Parkinson’s Disease, Alpha-synuclein, Desulfovibrio, and the Gut Microbiome. International Journal of Cell Biology and Cellular Functions. 2024; 02(01):18-28. Available from: https://journals.stmjournals.com/ijcbcf/article=2024/view=147928


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References

1. Nie S, Wang J, Deng Y, Ye Z, Ge Y. Inflammatory microbes and genes as potential biomarkers of Parkinson’s disease. NPJ Biofilms Microbiomes. 2022;8:101. DOI: 10.1038/s41522-022-00367-z. PubMed: 36564391.
2. Yamashita KY, Bhoopatiraju S, Silverglate BD, Grossberg GT. Biomarkers in Parkinson’s disease: A state of the art review. Biomark Neuropsychiatry. 2023;9. DOI: 10.1016/j.bionps.2023.100074.
3. Nakahara K, Nakane S, Ishii K, Ikeda T, Ando Y. Gut microbiota of Parkinson’s disease in an appendectomy cohort: A preliminary study. Sci Rep. 2023;13:2210. DOI: 10.1038/s41598-023-29219-2. PubMed: 36750613.
4. Ryman S, Vakhtin AA, Richardson SP, Lin HC. Microbiome–gut–brain dysfunction in prodromal and symptomatic Lewy body diseases. J Neurol. 2023;270(2):746-58. doi: 10.1007/s00415-022-11461-9. PubMed: 36355185.
5. 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. 2017;9:441. DOI: 10.3389/fnagi.2017.00441. PubMed: 29358918.
6. Ullah H, Arbab S, Tian Y, Liu CQ, Chen Y, Qijie L, Khan MIU, Hassan IU, Li K. The gut microbiota–brain axis in neurological disorder. Front Neurosci. 2023;17:1225875. doi: 10.3389/fnins.2023.1225875. PubMed: 37600019.
7. Liu J, Xu F, Nie Z, Shao L. Gut microbiota approach—A new strategy to treat Parkinson’s disease. Front Cell Infect Microbiol. 2020;10. DOI: 10.3389/fcimb.2020.570658.
8. Hey G, Nair N, Klann E, Gurrala A, Safarpour D, Mai V, et al. Therapies for Parkinson’s disease and the gut microbiome: Evidence for bidirectional connection. Front Aging Neurosci. 2023;15:1151850. DOI: 10.3389/fnagi.2023.1151850. PubMed: 37323145.
9. Rajput C, Sarkar A, Sachan N, Rawat N, Singh MP. Is gut dysbiosis an epicenter of Parkinson’s disease? Neurochem Res. 2021;46:425–38. DOI: 10.1007/s11064-020-03187-9. PubMed: 33400024.
10. Nowak JM, Kopczyński M, Friedman A, Koziorowski D, Figura M. Microbiota dysbiosis in Parkinson disease—in search of a biomarker. Biomedicines. 2022;10. DOI: 10.3390/biomedicines10092057. PubMed: 36140158.
11. Murros KE, Murros K. Hydrogen sulfide produced may induce Parkinson’s disease. Neurosci.
12. Camerucci E, Stang CD, Hajeb M, Turcano P, Mullan AF, Martin P, et al. Early-onset parkinsonism and early-onset Parkinson’s disease: A population-based study (2010–2015). J Parkinson’s Dis. 2021;11:1197–207. DOI: 10.3233/JPD-202279.
13. Sun MF, Shen YQ. Dysbiosis of gut microbiota and microbial metabolites in Parkinson’s disease. Ageing Res Rev. 2018;45:53–61. DOI: 10.1016/j.arr.2018.04.004.
14. Henderson MX, Trojanowski JQ, Lee VM. α-Synuclein pathology in Parkinson’s disease and related α-synucleinopathies. Neurosci Lett. 2019;709:134316. DOI: 10.1016/j.neulet.2019.134316. PubMed: 31170426.
15. Srinivasan E, Chandrasekhar G, Chandrasekar P, Anbarasu K, Vickram AS, Karunakaran R, et al. Alpha-synuclein aggregation in Parkinson’s disease. Front Med. 2021;8:736978. DOI: 10.3389/fmed.2021.736978. PubMed: 34733860.
16. Perez-Pardo P, Hartog M, Garssen J, Kraneveld AD. Microbes tickling your tummy: The importance of the gut-brain axis in Parkinson’s disease. Curr Behav Neurosci Rep. 2017;4:361–8. DOI: 10.1007/s40473-017-0129-2.
17. Hirayama M, Nishiwaki H, Hamaguchi T, Ohno K. Gastrointestinal disorders in Parkinson’s disease and other Lewy body diseases. npj Parkinsons Dis. 2023;9:71. doi: 10.1038/s41531-023-00511-2. PubMed: 37147392.
18. Singh Y, Trautwein C, Romani J, Salker MS, Neckel PH, Fraccaroli I, et al. Overexpression of human alpha-synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease. Mol Neurodegener. 2023;18. DOI: 10.1186/s13024-023-00628-1.
19. Huang Y, Liao J, Liu X, Zhong Y, Cai X, Long L. Review: The role of intestinal dysbiosis in Parkinson’s disease. Front Cell Infect Microbiol. 2021;11. DOI: 10.3389/fcimb.2021.615075.
20. Shen T, Yue Y, He T, Huang C, Qu B, Lv W, et al. The association between the gut microbiota and Parkinson’s disease: A meta-analysis. Front Aging Neurosci. 2021;13:636545. DOI: 10.3389/fnagi.2021.636545. PubMed: 33643026.
21. Savitt D, Jankovic J. Targeting α-synuclein in Parkinson’s disease: Progress towards the development of disease-modifying therapeutics. Drugs. 2019;79:797–810. DOI: 10.1007/s40265-019-01104-1. PubMed: 30982161.
22. Fitzgerald E, Murphy S, Martinson HA. Alpha-synuclein pathology and the role of the microbiota in Parkinson’s disease. Front Neurosci. 2019;13:369. DOI: 10.3389/fnins.2019.00369. PubMed: 31068777.
23. Chen ZJ, Liang CY, Yang LQ, Ren SM, Xia YM, Cui L, et al. Association of Parkinson’s disease with microbes and microbiological therapy. Front Cell Infect Microbiol. 2021;11. DOI: 10.3389/fcimb.2021.619354.
24. Fields CR, Bengoa-Vergniory N, Wade-Martins R. Targeting alpha-synuclein as a therapy for Parkinson’s disease. Front Mol Neurosci. 2019;12:299. doi: 10.3389/fnmol.2019.00299. PubMed: 31866823.
25. Munoz-Pinto MF, Empadinhas N, Cardoso SM. The neuromicrobiology of Parkinson’s disease: A unifying theory. Ageing Res Rev. 2021;70:101396. DOI: 10.1016/j.arr.2021.101396, PubMed: 34171417.
26. Zhu R, Luo Y, Li S, Wang Z. The role of microglial autophagy in Parkinson’s disease. Front Aging Neurosci. 2022;14:1039780. DOI: 10.3389/fnagi.2022.1039780, PubMed: 36389074.
27. Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Björklund T, et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014;128:805–20. DOI: 10.1007/s00401-014-1343-6, PubMed: 25296989.
28. Margolis KG, Cryan JF, Mayer EA. The microbiota-gut-brain axis: From motility to mood. Gastroenterology. 2021;160:1486–501. DOI: 10.1053/j.gastro.2020.10.066, PubMed: 33493503.
29. Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V. Alpha-synuclein in Parkinson’s disease and other synucleinopathies: From overt neurodegeneration back to early synaptic dysfunction. Cell Death Dis. 2023;14:176. DOI: 10.1038/s41419-023-05672-9, PubMed: 36859484.
30. Angius F, Mocci I, Ercoli T, Loy F, Fadda L, Palmas MF, et al. Combined measure of salivary alpha-synuclein species as diagnostic biomarker for Parkinson’s disease. J Neurol. 2023;270:5613–21. DOI: 10.1007/s00415-023-11893-x, PubMed: 37552278.
31. Grosso Jasutkar HG, Oh SE, Mouradian MM. Therapeutics in the pipeline targeting α-synuclein for Parkinson’s disease. Pharmacol Rev. 2022;74(1):207–37. doi: 10.1124/pharmrev.120.000133. PubMed: 35017177.
32. Kalyanaraman B, Cheng G, Hardy M. Gut microbiome, short-chain fatty acids, alpha-synuclein, neuroinflammation, and ROS/RNS: Relevance to Parkinson’s disease and therapeutic implications. Redox Biol. 2024;71:103092. DOI: 10.1016/j.redox.2024.103092, PubMed: 38377788.
33. Knorr D, Sinskey AJ. Biotechnology in food production and processing. Science. 1985;229(4719):
1224-9. doi: 10.1126/science.229.4719.1224. PubMed: 17770800.
34. Ray B, Mahalakshmi AM, Tuladhar S, Bhat A, Srinivasan A, Pellegrino C, et al. “Janus-faced” α-synuclein: Role in Parkinson’s disease. Front Cell Dev Biol. 2021;9:673395. DOI: 10.3389/fcell.
2021.673395.
35. Martin-Gallausiaux C, Marinelli L, Blottière HM, Larraufie P, Lapaque N. SCFA: Mechanisms and functional importance in the gut. Proc Nutr Soc. 2021;37–49.
36. Zhu M, Liu X, Ye Y, Yan X, Cheng Y, Zhao L, et al. Gut microbiota: A mechanistic regulator of neurogenesis and therapy in Parkinson’s disease. Neural Regen Res. 2023;18:1684–94. DOI: 10.4103/1673-5374.358304, PubMed: 37074718.
37. Baizabal-Carvallo JF, Alonso-Juarez M. The link between gut dysbiosis and neuroinflammation in Parkinson’s disease. Neuroscience. 2020;432:160–73. DOI: 10.1016/j.neuroscience.2020.02.030, PubMed: 32112917.
38. Metta V, Leta V, Mrudula KR, Prashanth LK, Goyal V, Borgohain R, et al. Gastrointestinal dysfunction in Parkinson’s disease: Molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation. J Neurol. 2022;269:1154–63. DOI: 10.1007/s00415-021-10567-w, PubMed: 33881598.
39. Bi M, Feng L, He J, Liu C, Wang Y, Jiang H, Liu SJ. Emerging insights between gut microbiome dysbiosis and Parkinson’s disease: Pathogenic and clinical relevance. Ageing Res Rev. 2022;82:101759. doi: 10.1016/j.arr.2022.101759. PubMed: 36243356.
40. Jackson A, Forsyth CB, Shaikh M, Voigt RM, Engen PA, Ramirez V, et al. Diet in Parkinson’s disease: Critical role for the microbiome. Front Neurol. 2019;10:1245. DOI: 10.3389/fneur.2019.01245, PubMed: 31920905.
41. Xie A, Ensink E, Li P, Gordevičius J, Marshall LL, George S, et al. Bacterial butyrate in Parkinson’s disease is linked to epigenetic changes and depressive symptoms. Mov Disord. 2022;37:1644–53. DOI: 10.1002/mds.29128, PubMed: 35723531.
42. Cirstea MS, Yu AC, Golz E, Sundvick K, Kliger D, Radisavljevic N, Foulger LH, Mackenzie M, Huan T, Finlay BB, Appel-Cresswell S. Microbiota composition and metabolism are associated with gut function in Parkinson’s disease. Mov Disord. 2020;35(7):1208-17. doi: 10.1002/mds.
28052. PubMed: 32357258.
43. Thangaleela S, Sivamaruthi BS, Kesika P, Bharathi M, Chaiyasut C. Role of the gut–brain axis, gut microbial composition, diet, and probiotic intervention in Parkinson’s disease. Microorganisms. 2022;10:1544. DOI: 10.3390/microorganisms10081544, PubMed: 36013962.
44. Elford JD, Becht N, Garssen J, Kraneveld AD, Perez-Pardo P. Buty and the beast: The complex role of butyrate in Parkinson’s disease. Front Pharmacol. 2024;15:1388401. DOI: 10.3389/fphar.
2024.1388401, PubMed: 38694925.
45. Murros KE, Huynh VA, Takala TM, Saris PEJ. Desulfovibrio bacteria are associated with Parkinson’s disease. Front Cell Infect Microbiol. 2021;11:652617. DOI: 10.3389/fcimb.2021.652617.
46. Sittipo P, Choi J, Lee S, Lee YK. The function of gut microbiota in immune-related neurological disorders: A review. J Neuroinflammation. 2022;19(1):154. doi: 10.1186/s12974-022-02510-1. PubMed: 35706008.
47. Santos SF, De Oliveira HL, Yamada ES, Neves BC, Pereira A Jr. The Gut and Parkinson’s Disease-A Bidirectional Pathway. Front Neurol. 2019;10:574. doi: 10.3389/fneur.2019.00574. PubMed: 31214110.
48. Suganya K, Koo BS. Gut–brain axis: Role of gut microbiota on neurological disorders and how probiotics/prebiotics beneficially modulate microbial and immune pathways to improve brain functions. Int J Mol Sci. 2020;21(20):7551. doi: 10.3390/ijms21207551. PubMed: 33066156.
49. Wang Q, Luo Y, Ray Chaudhuri K, Reynolds R, Tan EK, Pettersson S. The role of gut dysbiosis in Parkinson’s disease: Mechanistic insights and therapeutic options. Brain. 2021;144:2571–93. DOI: 10.1093/brain/awab156, PubMed: 33856024.
50. Zhang F, Wang D. Potential of Akkermansia muciniphila and its outer membrane proteins as therapeutic targets for neuropsychological diseases. Front Microbiol. 2023;14:1191445. DOI: 10.3389/fmicb.2023.1191445, PubMed: 37440890.
51. Hirayama M, Ohno K. Parkinson’s disease and gut microbiota. Ann Nutr Metab. 2021;77(Suppl 2):28–35. DOI: 10.1159/000518147, PubMed: 34500451.
52. Hashish S, Salama M. The role of an altered gut microbiome in Parkinson’s disease: A narrative review. Appl Microbiol. 2023;3:429–47. DOI: 10.3390/applmicrobiol3020030.
53. Singh SB, Carroll-Portillo A, Lin HC. Desulfovibrio in the gut: The enemy within? Microorganisms. 2023;11:1772. DOI: 10.3390/microorganisms11071772.
54. Muyzer G, Stams AJM. The ecology and biotechnology of sulphate-reducing bacteria. Nat Rev Microbiol. 2008;6:441–54. DOI: 10.1038/nrmicro1892, PubMed: 18461075.
55. Dordević D, Jančíková S, Vítězová M, Kushkevych I. Hydrogen sulfide toxicity in the gut environment: Meta-analysis of sulfate-reducing and lactic acid bacteria in inflammatory processes. J Adv Res. 2021;27:55–69. DOI: 10.1016/j.jare.2020.03.003, PubMed: 33318866.
56. Huynh VA, Takala TM, Murros KE, Diwedi B, Saris PEJ. Desulfovibrio bacteria enhance alpha-synuclein aggregation in a Caenorhabditis elegans model of Parkinson’s disease. Front Cell Infect Microbiol. 2023;13:1181315. DOI: 10.3389/fcimb.2023.1181315, PubMed: 37197200.
57. Bing G, Liu M. Lipopolysaccharide animal models for Parkinson’s disease. Parkinson’s Dis. 2011.
58. Rose AH. The microbiological production of food and drink. Sci Am. 1981;245(3):126-39. doi: 10.1038/scientificamerican0981-126. PubMed: 6895124.
59. Gorecki AM, Preskey L, Bakeberg MC, Kenna JE, Gildenhuys C, MacDougall G, Dunlop SA, Mastaglia FL, Akkari PA, Koengten F, Anderton RS. Altered gut microbiome in Parkinson’s disease and the influence of lipopolysaccharide in a human α-synuclein over-expressing mouse model. Frontiers in neuroscience. 2019 Aug 7;13:839.
60. Gorecki AM, Preskey L, Bakeberg MC, Kenna JE, Gildenhuys C, MacDougall G, Dunlop SA, Mastaglia FL, Akkari PA, Koengten F, Anderton RS. Altered gut microbiome in Parkinson’s disease and the influence of lipopolysaccharide in a human α-synuclein over-expressing mouse model. Front Neurosci. 2019;13:839. doi: 10.3389/fnins.2019.00839. PubMed: 31440136.


Regular Issue Subscription Review Article
Volume 02
Issue 01
Received 20/04/2024
Accepted 22/05/2024
Published 27/05/2024


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