Document Type : Review Article


1 Faculty of Pharmacy and Biochemistry, National University of San Marcos, Lima 03, Peru

2 Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

3 Faculty of Pharmacy, Pontifical Catholic University of Peru, Lima 03, Peru


It is possible for the non-motor symptoms (NMS) of Parkinson's disease (PD), which include constipation, sleep difficulties, and olfactory impairments, to appear up to 20 years before the motor symptoms of the disease. There is a growing body of research that suggests the pathology of Parkinson's disease may begin in the gastrointestinal tract and progress to the brain. Numerous studies provide credence to the idea that the microbiota in one's gut communicates with one's brain in Parkinson's disease (PD) via way of the immune system, a certain amino acid metabolism, and the neurological system. Through what has become known as the "gut microbiota-brain axis" (GMBA), the gut microbiota is thought to play an important part in the modulation of several neurochemical pathways.In the process of mediating the crosstalk between the gut microbiota and the physiology of the host, many of the metabolites produced by the gut microbiota, such as fatty acids, amino acids, and bile acids, carry signaling activities. In Parkinson's disease (PD), the quantity of amino acids and species-specific alterations of amino acids, such as glutamate and tryptophan, may interfere with the signaling transmission between nerve cells and disrupt the normal operation of the basal ganglia. Certain amino acids and the receptors that bind to them are being looked at as new possible targets for the treatment of PD. The purpose of the current investigation was to compile and analyze all of the evidence that is currently available on the gut microbiota-derived amino acid metabolic changes that are related with PD.

Graphical Abstract

Gut microbiota and parkinson's disease


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ِDr. Mohammad Reza Mohammadi
Tarbiat Modares University

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  1. Goralczyk-Binkowska A, Szmajda-Krygier D, Kozlowska E (2022) The Microbiota-Gut-Brain Axis in Psychiatric Disorders. Int J Mol Sci 23 (19). doi:
  2. Li C, Liang Y, Qiao Y (2022) Messengers From the Gut: Gut Microbiota-Derived Metabolites on Host Regulation. Front Microbiol 13: 863407. doi:
  3. Ortega MA, Alvarez-Mon MA, Garcia-Montero C, Fraile-Martinez O, Guijarro LG, Lahera G, Monserrat J, Valls P, Mora F, Rodriguez-Jimenez R, Quintero J, Alvarez-Mon M (2022) Gut Microbiota Metabolites in Major Depressive Disorder-Deep Insights into Their Pathophysiological Role and Potential Translational Applications. Metabolites 12 (1). doi:
  4. Pinheiro Campos AC, Martinez RCR, Auada AVV, Lebrun I, Fonoff ET, Hamani C, Pagano RL (2022) Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson's Disease Rat Model. Int J Mol Sci 23 (20). doi:
  5. Sun Y, Wang S, Liu B, Hu W, Zhu Y (2023) Host-Microbiome Interactions: Tryptophan Metabolism and Aromatic Hydrocarbon Receptors after Traumatic Brain Injury. Int J Mol Sci 24 (13). doi:
  6. Tamura H, Nishio R, Saeki N, Katahira M, Morioka H, Tamano H, Takeda A (2022) Paraquat-induced intracellular Zn(2+) dysregulation causes dopaminergic degeneration in the substantia nigra, but not in the striatum. Neurotoxicology 90: 136-144. doi:
  7. Tseng KY, Kuo TT, Wang V, Huang EY, Ma KH, Olson L, Hoffer BJ, Chen YH (2022) Tetrabenazine Mitigates Aberrant Release and Clearance of Dopamine in the Nigrostriatal System, and Alleviates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease. Journal of Parkinson's disease 12 (5): 1545-1565. doi:
  8. Wang W, Jiang S, Xu C, Tang L, Liang Y, Zhao Y, Zhu G (2022) Interactions between gut microbiota and Parkinson's disease: The role of microbiota-derived amino acid metabolism. Front Aging Neurosci 14: 976316. doi:
  9. Choi SM, Cho SH, Kang KW, Kim JM, Kim BC (2021) Family history of hand tremor in patients with early Parkinson's disease. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 90: 161-164. doi:
  10. Choudhury GR, Daadi MM (2018) Charting the onset of Parkinson-like motor and non-motor symptoms in nonhuman primate model of Parkinson's disease. PLoS One 13 (8): e0202770. doi:
  11. Savitt J, Aouchiche R (2020) Management of Visual Dysfunction in Patients with Parkinson's Disease. Journal of Parkinson's disease 10 (s1): S49-s56. doi:
  12. Fereshtehnejad S-M, Romenets SR, Anang JB, Latreille V, Gagnon J-F, Postuma RB (2015) New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA neurology 72 (8): 863-873. doi:
  13. Tofaris GK, Goedert M, Spillantini MG (2017) The transcellular propagation and intracellular trafficking of α-synuclein. Cold Spring Harbor perspectives in medicine 7 (9): a024380. doi:
  14. Grazia Spillantini M, Anthony Crowther R, Jakes R, Cairns NJ, Lantos PL, Goedert M (1998) Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies. Neuroscience Letters 251 (3): 205-208. doi:
  15. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proceedings of the National Academy of Sciences 95 (11): 6469-6473. doi:
  16. Furness JB, Callaghan BP, Rivera LR, Cho H-J (2014) The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control. In: Lyte M, Cryan JF (eds) Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease. Springer New York, New York, NY, pp 39-71. doi:
  17. Qu Z-D, Thacker M, Castelucci P, Bagyanszki M, Epstein ML, Furness JB (2008) Immunohistochemical analysis of neuron types in the mouse small intestine. Cell and tissue research 334 (2): 147-161. doi:
  18. Gulbransen BD, Sharkey KA (2012) Novel functional roles for enteric glia in the gastrointestinal tract. Nature reviews Gastroenterology & hepatology 9 (11): 625-632. doi:
  19. Grundmann D, Loris E, Maas‐Omlor S, Huang W, Scheller A, Kirchhoff F, Schäfer KH (2019) Enteric glia: S100, GFAP, and beyond. The Anatomical Record 302 (8): 1333-1344. doi:
  20. Bhukya S, S S, S S, J AQ, A A, Rani N, K D, A D, Nag TC, A S (2021) Morphological changes of the myenteric plexus at different gut segments of human fetuses. Journal of histotechnology 44 (3): 150-159. doi:
  21. Pan W, Rahman AA, Stavely R, Bhave S, Guyer R, Omer M, Picard N, Goldstein AM, Hotta R (2022) Schwann Cells in the Aganglionic Colon of Hirschsprung Disease Can Generate Neurons for Regenerative Therapy. Stem cells translational medicine 11 (12): 1232-1244. doi:
  22. Sanchini G, Vaes N, Boesmans W (2023) Mini-review: Enteric glial cell heterogeneity: Is it all about the niche? Neurosci Lett 812: 137396. doi:
  23. Smith M, Chhabra S, Shukla R, Kenny S, Almond S, Edgar D, Wilm B (2023) The transition zone in Hirschsprung's bowel contains abnormal hybrid ganglia with characteristics of extrinsic nerves. J Cell Mol Med 27 (2): 287-298. doi:
  24. Spencer NJ, Hu H (2020) Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nature reviews Gastroenterology & hepatology 17 (6): 338-351. doi:
  25. Endres K, Schäfer K-H (2018) Influence of commensal microbiota on the enteric nervous system and its role in neurodegenerative diseases. Journal of innate immunity 10 (3): 172-180. doi:
  26. Blanco AM, Calo J, Soengas JL (2021) The gut-brain axis in vertebrates: implications for food intake regulation. The Journal of experimental biology 224 (Pt 1). doi:
  27. Hill AE, Wade-Martins R, Burnet PWJ (2021) What Is Our Understanding of the Influence of Gut Microbiota on the Pathophysiology of Parkinson's Disease? Front Neurosci 15: 708587. doi:
  28. Matsubara Y, Kiyohara H, Teratani T, Mikami Y, Kanai T (2022) Organ and brain crosstalk: The liver-brain axis in gastrointestinal, liver, and pancreatic diseases. Neuropharmacology 205: 108915. doi:
  29. Navarro A, Boveris A (2009) Brain mitochondrial dysfunction and oxidative damage in Parkinson’s disease. Journal of Bioenergetics and Biomembranes 41: 517-521. doi:
  30. Browning KN, Carson KE (2021) Central Neurocircuits Regulating Food Intake in Response to Gut Inputs-Preclinical Evidence. Nutrients 13 (3). doi:
  31. Neuhuber WL, Berthoud HR (2022) Functional anatomy of the vagus system: How does the polyvagal theory comply? Biological psychology 174: 108425. doi:
  32. van Weperen VYH, Vaseghi M (2023) Cardiac vagal afferent neurotransmission in health and disease: review and knowledge gaps. Front Neurosci 17: 1192188. doi:
  33. Imai J, Katagiri H (2022) Regulation of systemic metabolism by the autonomic nervous system consisting of afferent and efferent innervation. International immunology 34 (2): 67-79. doi:
  34. Minic Z, O'Leary DS, Reynolds CA (2022) Spinal Reflex Control of Arterial Blood Pressure: The Role of TRP Channels and Their Endogenous Eicosanoid Modulators. Front Physiol 13: 838175. doi:
  35. Wachsmuth HR, Weninger SN, Duca FA (2022) Role of the gut-brain axis in energy and glucose metabolism. Experimental & molecular medicine 54 (4): 377-392. doi:
  36. Goronzy JJ, Li G, Yang Z, Weyand CM (2013) The janus head of T cell aging–autoimmunity and immunodeficiency. Frontiers in immunology 4: 131. doi:
  37. Calabrese V, Santoro A, Monti D, Crupi R, Di Paola R, Latteri S, Cuzzocrea S, Zappia M, Giordano J, Calabrese EJ (2018) Aging and Parkinson's Disease: Inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radical Biology and Medicine 115: 80-91. doi:
  38. Mészáros Á, Molnár K, Nógrádi B, Hernádi Z, Nyúl-Tóth Á, Wilhelm I, Krizbai IA (2020) Neurovascular inflammaging in health and disease. Cells 9 (7): 1614. doi:
  39. Zhu M, Liu X, Ye Y, Yan X, Cheng Y, Zhao L, Chen F, Ling Z (2022) Gut microbiota: a novel therapeutic target for Parkinson’s disease. Frontiers in Immunology 13: 937555. doi:
  40. Braak H, Tredici KD, Rüb U, de Vos RAI, Jansen Steur ENH, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging 24 (2): 197-211. doi:
  41. Noyce AJ, Bestwick JP, Silveira‐Moriyama L, Hawkes CH, Giovannoni G, Lees AJ, Schrag A (2012) Meta‐analysis of early nonmotor features and risk factors for Parkinson disease. Annals of neurology 72 (6): 893-901. doi:
  42. Romano S, Savva GM, Bedarf JR, Charles IG, Hildebrand F, Narbad A (2021) Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation. npj Parkinson's Disease 7 (1): 27. doi:
  43. Houser MC, Tansey MG (2017) The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinson's disease 3 (1): 3. doi:
  44. Dodiya HB, Forsyth CB, Voigt RM, Engen PA, Patel J, Shaikh M, Green SJ, Naqib A, Roy A, Kordower JH, Pahan K, Shannon KM, Keshavarzian A (2020) Chronic stress-induced gut dysfunction exacerbates Parkinson's disease phenotype and pathology in a rotenone-induced mouse model of Parkinson's disease. Neurobiol Dis 135: 104352. doi:
  45. Gerhardt S, Mohajeri MH (2018) Changes of Colonic Bacterial Composition in Parkinson's Disease and Other Neurodegenerative Diseases. Nutrients 10 (6). doi:
  46. Li C, Cui L, Yang Y, Miao J, Zhao X, Zhang J, Cui G, Zhang Y (2019) Gut Microbiota Differs Between Parkinson's Disease Patients and Healthy Controls in Northeast China. Front Mol Neurosci 12: 171. doi:
  47. Romano S, Savva GM, Bedarf JR, Charles IG, Hildebrand F, Narbad A (2021) Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation. NPJ Parkinsons Dis 7 (1): 27. doi:
  48. Aho VT, Pereira PA, Voutilainen S, Paulin L, Pekkonen E, Auvinen P, Scheperjans F (2019) Gut microbiota in Parkinson's disease: temporal stability and relations to disease progression. EBioMedicine 44: 691-707. doi:
  49. Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola‐Rautio J, Pohja M (2015) Gut microbiota are related to Parkinson's disease and clinical phenotype. Movement Disorders 30 (3): 350-358. doi:
  50. Bhattarai Y, Kashyap PC (2020) Parkinson’s disease: Are gut microbes involved? American Journal of Physiology-Gastrointestinal and Liver Physiology 319 (5): G529-G540. doi:
  51. Boertien JM, Pereira PA, Aho VT, Scheperjans F (2019) Increasing comparability and utility of gut microbiome studies in Parkinson’s disease: a systematic review. Journal of Parkinson's disease 9 (s2): S297-S312. doi:
  52. Heinzel S, Aho VT, Suenkel U, von Thaler AK, Schulte C, Deuschle C, Paulin L, Hantunen S, Brockmann K, Eschweiler GW (2021) Gut microbiome signatures of risk and prodromal markers of Parkinson disease. Annals of neurology 90 (3): E1-E12. doi:
  53. Houser MC, Chang J, Factor SA, Molho ES, Zabetian CP, Hill‐Burns EM, Payami H, Hertzberg VS, Tansey MG (2018) Stool immune profiles evince gastrointestinal inflammation in Parkinson's disease. Movement Disorders 33 (5): 793-804. doi:
  54. Mulak A, Koszewicz M, Panek-Jeziorna M, Koziorowska-Gawron E, Budrewicz S (2019) Fecal calprotectin as a marker of the gut immune system activation is elevated in Parkinson’s disease. Frontiers in neuroscience 13: 992. doi:
  55. Ahrodia T, Das S, Bakshi S, Das B (2022) Structure, functions, and diversity of the healthy human microbiome. Progress in molecular biology and translational science 191 (1): 53-82. doi:
  56. Shao Y, Jiang Y, Li H, Zhang F, Hu Z, Zheng S (2021) Characteristics of mouse intestinal microbiota during acute liver injury and repair following 50% partial hepatectomy. Experimental and therapeutic medicine 22 (3): 953. doi:
  57. Wang D (2023) Metagenomics Databases for Bacteria. Methods in molecular biology (Clifton, NJ) 2649: 55-67. doi:
  58. Cirstea MS, Yu AC, Golz E, Sundvick K, Kliger D, Radisavljevic N, Foulger LH, Mackenzie M, Huan T, Finlay BB (2020) Microbiota composition and metabolism are associated with gut function in Parkinson's disease. Movement Disorders 35 (7): 1208-1217. doi:
  59. Wallen ZD, Appah M, Dean MN, Sesler CL, Factor SA, Molho E, Zabetian CP, Standaert DG, Payami H (2020) Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens. npj Parkinson's Disease 6 (1): 11. doi:
  60. Hasegawa S, Goto S, Tsuji H, Okuno T, Asahara T, Nomoto K, Shibata A, Fujisawa Y, Minato T, Okamoto A (2015) Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson’s disease. PloS one 10 (11): e0142164. doi:
  61. Minato T, Maeda T, Fujisawa Y, Tsuji H, Nomoto K, Ohno K, Hirayama M (2017) Progression of Parkinson's disease is associated with gut dysbiosis: two-year follow-up study. PloS one 12 (11): e0187307. doi:
  62. Zeissig S, Bürgel N, Günzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2007) Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut 56 (1): 61-72. doi:
  63. Yang D, Zhao D, Ali Shah SZ, Wu W, Lai M, Zhang X, Li J, Guan Z, Zhao H, Li W (2019) The role of the gut microbiota in the pathogenesis of Parkinson's disease. Frontiers in neurology 10: 1155. doi:
  64. Clairembault T, Leclair-Visonneau L, Coron E, Bourreille A, Le Dily S, Vavasseur F, Heymann M-F, Neunlist M, Derkinderen P (2015) Structural alterations of the intestinal epithelial barrier in Parkinson’s disease. Acta neuropathologica communications 3: 1-9. doi:
  65. Schwiertz A, Spiegel J, Dillmann U, Grundmann D, Bürmann J, Faßbender K, Schäfer K-H, Unger MM (2018) Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease. Parkinsonism & Related Disorders 50: 104-107. doi:
  66. Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A (2011) Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PloS one 6 (12): e28032. doi:
  67. Trist BG, Hare DJ, Double KL (2019) Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease. Aging cell 18 (6): e13031. doi:
  68. Ambrosi G, Cerri S, Blandini F (2014) A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease. Journal of neural transmission 121: 849-859. doi:
  69. Lindahl M, Chalazonitis A, Palm E, Pakarinen E, Danilova T, Pham TD, Setlik W, Rao M, Võikar V, Huotari J, Kopra J, Andressoo J-O, Piepponen PT, Airavaara M, Panhelainen A, Gershon MD, Saarma M (2020) Cerebral dopamine neurotrophic factor–deficiency leads to degeneration of enteric neurons and altered brain dopamine neuronal function in mice. Neurobiology of Disease 134: 104696. doi:
  70. Lee H-C, Wei Y-H (2005) Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. The International Journal of Biochemistry & Cell Biology 37 (4): 822-834. doi:
  71. Barodia SK, Creed RB, Goldberg MS (2017) Parkin and PINK1 functions in oxidative stress and neurodegeneration. Brain research bulletin 133: 51-59. doi: