GUT-MICROBIOME-BRAIN AXIS AND ITS INFLUENCE ON PARKINSON'S DISEASE (Review Article)
The relationship between the nervous system and microbiota opened up research opportunities that can significantly change the management of several neurological disorders. The discovery of the microbiota-gut-brain axis helped us understand how the information is relayed between the brain and the enteric nervous system. This connection demonstrated how, in Parkinson’s disease, the alpha- synuclein accumulates in different organs, resulting in a wide array of symptoms. Moreover, pathways such as the hypothalamic-pituitary axis, the neuroinflammatory pathway, and neuroactive molecules are associated with the pathophysiology of PD. The manifestation of gastrointestinal symptoms and altered gut microbiota have been noted in patients several years before other significant clinical symptoms appeared. The role of alpha-synuclein accumulation and environmental factors that disrupt the natural flora of the gut in the overall progression of PD has been observed through well documented clinical studies on mice. With the current knowledge that has been established, the alteration of gut microbiota using recently explored treatment options such as probiotics, fecal microbiota transplantation, dietary changes, and certain antibiotics can prevent the progressive symptoms of Parkinson's disease.
Andrews ZB, Erion D, Beiler R, Liu ZW, Abizaid A, Zigman J, Elsworth JD, Savitt JM, DiMarchi R, Tschoep M, Roth RH, Gao XB, Horvath TL. Ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. JNeurosci 2009 Nov 11;29(45):14057-65
Nair AT, Ramachandran V, Joghee NM, Antony S, Ramalingam G. Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review. J Neurogastroenterol Motil 2018;24(1):30-42
Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut. 2019 Aug;68(8):1516-1526
Caputi V, Giron MC. Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson's Disease. Int J Mol Sci 2018 Jun 6;19(6):1689
Corrigan, M., Roberts, K. and Steiger, E., n.d. Adult short bowel syndrome. 2018 Published: October 9, 2018; Imprint: Academic Press; Paperback ISBN: 9780128143308
Del Chierico F, Vernocchi P, Dallapiccola B, Putignani L. Mediterranean diet and health: food effects on gut microbiota and disease control. Int J Mol Sci 2014;15(7):11678-11699.
Du Y, Ma Z, Lin S, et al. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. Proc Natl Acad (USA) 2001;98(25):14669-14674
Jęśko H, Lenkiewicz AM, Wilkaniec A, Adamczyk A. The interplay between parkinand alpha-synuclein; possible implications for the pathogenesis of Parkinson's disease. Acta Neurobiol Exp (Wars). 2019;79(3):276-289
Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci 2015; 9:392.
Keshavarzian A., Green S.J., Engen P.A., Voigt R.M., Naqib A., Forsyth C.B., Mutlu E., Shannon K.M. Colonic bacterial composition in Parkinson’s disease. Mov Disord 2015; 30:1351–1360.
Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J PhysiolPharmacol 2011 Dec;62(6):591-9
Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: A Swedishregister- based matched-cohort study. Neurology. 2017;88(21):1996-2002
Masuda-Suzukake M, Hasegawa M. Prion-like Propagation of Pathological α-Synuclein in Vivo. YakugakuZasshi. 2019;139(7):1007-1013
Mohajeri MH, Fata GL, Steinert RE, Weber P, Relationship between the gut microbiome and brain function, NutrRev2018; 76(7):481–496
Obrenovich MEM. Leaky Gut, Leaky Brain? Microorganisms. 2018;6(4):107
Osadchiy V, Martin CR, Mayer EA. The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications. Clin Gastroenterol Hepatol 2019 Jan;17(2):322-332.
Parkinson’s Foundation. 2021. Common Genetic Mutations: https://www.parkinson.org/understanding-parkinsons/causes/genetics/common-genetic-mutations
Parkinson’s Foundation. 2021. Statistics - https://www.parkinson.org/Understanding-Parkinsons/Statistics
Parkinson's Foundation. 2021. Environmental Factors -https://www.parkinson.org/Understanding-Parkinsons/Causes/Environmental-Factors
Perez-Pardo P, Dodiya HB, Engen PA, Naqib A, Forsyth CB, Green SJ, Garssen J, Keshavarzian A, Kraneveld AD. Gut bacterial composition in a mouse model of Parkinson's disease. Benef Microbes 2018 Sep 18;9(5):799-814
Perez-Pardo P; KliestT; DodiyaHB; Broersen LM; GarssenJ; KeshavarzianA; Kraneveld AD/ The gut-brain axis in parkinson's disease: Possibilities for food-based therapies. Jur J Pharmacol 2017 Dec; 15; 817:86-95
Seguella L, Sarnelli G, Esposito G. Leaky gut, dysbiosis, and enteric glia activation: the trilogy behind the intestinal origin of Parkinson's disease. Neural Regen Res 2020;15(6):1037- 1038
Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short- chain fatty acids in health and disease. Adv Immunol 2014; 121:91-119
Turnbull AV, Rivier C. Regulation of the HPA axis by cytokines. BrainBehavImmun.1995Dec;9(4):253-75
Ulusoy A, Phillips RJ, Helwig M, Klinkenberg M, Powley TL, Di Monte DA. Brain-to-stomach transfer of α-synuclein via vagal preganglionic projections. Acta Neuropathol 2017;133(3):381-393
Yang F, Wolk A, Håkansson N, Pedersen NL, Wirdefeldt K. Dietary antioxidants and risk of Parkinson's disease in two population-based cohorts. Mov Disord 2017;32(11):1631-1636