Role of the microbiome in the development of Parkinson's disease (Review)

Gushi,Sofjana; Derdas,Stavros P.

doi:10.3892/wasj.2025.374

Role of the microbiome in the development of Parkinson's disease (Review)

Authors:
- Sofjana Gushi
- Stavros P. Derdas
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Affiliations: KARYO Ltd., Molecular Diagnostics Laboratory, 54623 Thessaloniki, Greece, Department of Dietetics, School of Health, Aegean College, 10564 Athens, Greece
Published online on: July 14, 2025 https://doi.org/10.3892/wasj.2025.374
Article Number: 86
Copyright : © Gushi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Parkinson's disease (PD) is a disorder of the brain marked by the gradual loss of dopaminergic neurons in the substantia nigra, resulting in both motor and non‑motor symptoms. Emerging evidence indicates that the gut microbiota plays a crucial role in the development and progression of Parkinson's disease. The present review discusses the function of the gut microbiome in PD, including its makeup, interactions with the host and putative processes that relate microbial dysbiosis to neurodegeneration. In addition, the present review discusses the possibilities of diagnostic biomarkers and microbiome‑targeted therapeutics for PD. The present review synthesizes scientific literature data using a case‑control approach to provide a summary of the composition of the gut microbiota in patients with PD and healthy controls. The present review includes microbiological, clinical and biomarker data in an aim to provide a better understanding of the gut‑brain axis and its implications. Patients with PD have a lower microbial diversity and changes in certain bacterial communities, such as lower amounts of Prevotellaceae and greater amounts of Enterobacteriaceae. Dysbiosis can cause α‑synuclein misfolding, neuroinflammation and increased intestinal permeability, potentially leading to the development of PD through the gut‑brain axis. Probiotics, dietary changes and fecal microbiota transplantation all show promise for restoring microbial balance and relieving PD symptoms. Advances in metagenomics and artificial intelligence‑driven analysis help to clarify microbiome‑based therapies. The gut microbiota affects the gut‑brain axis, neuroinflammation and α‑synuclein aggregation, all of which contribute to the development of PD. Targeted microbiome therapeutics have the potential to improve illness management; however, more standardized, long‑term trials are required to determine causation and therapeutic effectiveness. The present review emphasizes the relevance of personalized techniques and modern technology in microbiome research for PD.

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1	Dorsey ER, Sherer T, Okun MS and Bloem BR: The emerging evidence of the Parkinson pandemic. J Parkinsons Dis. 8 (Suppl 1):S3–S8. 2018.PubMed/NCBI View Article : Google Scholar
2	Kalia LV and Lang AE: Parkinson's disease. Lancet. 386:896–912. 2015.PubMed/NCBI View Article : Google Scholar
3	Tolosa E, Garrido A, Scholz SW and Poewe W: Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 20:385–397. 2021.PubMed/NCBI View Article : Google Scholar
4	Cabreira V and Massano J: Parkinson's Disease: Clinical Review and Update. Acta Med Port. 32:661–670. 2019.PubMed/NCBI View Article : Google Scholar : (In Portuguese).
5	Gushi S and Balis V: Mitochondrial inherited disorders and their correlation with neurodegenerative diseases. Endocr Metab Immune Disord Drug Targets. 24:381–393. 2024.PubMed/NCBI View Article : Google Scholar
6	Jankovic J and Tan EK: Parkinson's disease: Etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry. 91:795–808. 2020.PubMed/NCBI View Article : Google Scholar
7	Coukos R and Krainc D: Key genes and convergent pathogenic mechanisms in Parkinson disease. Nat Rev Neurosci. 25:393–413. 2024.PubMed/NCBI View Article : Google Scholar
8	Cerri S, Mus L and Blandini F: Parkinson's disease in women and men: What's the difference? J Parkinsons Dis. 9:501–515. 2019.PubMed/NCBI View Article : Google Scholar
9	Bloem BR, Okun MS and Klein C: Parkinson's disease. Lancet. 397:2284–2303. 2021.PubMed/NCBI View Article : Google Scholar
10	Pajares M, Rojo AI, Manda G, Boscá L and Cuadrado A: Inflammation in Parkinson's disease: Mechanisms and therapeutic implications. Cells. 9(1687)2020.PubMed/NCBI View Article : Google Scholar
11	Elsworth JD: Parkinson's disease treatment: Past, present, and future. J Neural Transm (Vienna). 127:785–791. 2020.PubMed/NCBI View Article : Google Scholar
12	Keenan MJ, Marco ML, Ingram DK and Martin RJ: Improving healthspan via changes in gut microbiota and fermentation. Age (Dordr). 37(98)2015.PubMed/NCBI View Article : Google Scholar
13	Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV and Knight R: Current understanding of the human microbiome. Nat Med. 24:392–400. 2018.PubMed/NCBI View Article : Google Scholar
14	Cani PD: Human gut microbiome: Hopes, threats and promises. Gut. 67:1716–1725. 2018.PubMed/NCBI View Article : Google Scholar
15	Jain A, Madkan S and Patil P: The role of gut microbiota in neurodegenerative diseases: Current insights and therapeutic implications. Cureus. 15(e47861)2023.PubMed/NCBI View Article : Google Scholar
16	Olanow CW and Schapira AH: Therapeutic prospects for Parkinson disease. Ann Neurol. 74:337–347. 2013.PubMed/NCBI View Article : Google Scholar
17	Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, et al: The microbiota-gut-brain axis. Physiol Rev. 99:1877–2013. 2019.PubMed/NCBI View Article : Google Scholar
18	Zhu X, Han Y, Du J, Liu R, Jin K and Yi W: Microbiota-gut-brain axis and the central nervous system. Oncotarget. 8:53829–53838. 2017.PubMed/NCBI View Article : Google Scholar
19	Mayer EA, Knight R, Mazmanian SK, Cryan JF and Tillisch K: Gut microbes and the brain: Paradigm shift in neuroscience. J Neurosci. 34:15490–15496. 2014.PubMed/NCBI View Article : Google Scholar
20	Haase S, Wilck N, Haghikia A, Gold R, Mueller DN and Linker RA: The role of the gut microbiota and microbial metabolites in neuroinflammation. Eur J Immunol. 50:1863–1870. 2020.PubMed/NCBI View Article : Google Scholar
21	Klann EM, Dissanayake U, Gurrala A, Farrer M, Shukla AW, Ramirez-Zamora A, Mai V and Vedam-Mai V: The gut-brain axis and its relation to Parkinson's disease: A review. Front Aging Neurosci. 13(782082)2022.PubMed/NCBI View Article : Google Scholar
22	Lynch SV and Pedersen O: The human intestinal microbiome in health and disease. N Engl J Med. 375:2369–2379. 2016.PubMed/NCBI View Article : Google Scholar
23	Shannon KM: Gut-derived sterile inflammation and Parkinson's disease. Front Neurol. 13(831090)2022.PubMed/NCBI View Article : Google Scholar
24	Hirayama M and Ohno K: Parkinson's disease and gut microbiota. Ann Nutr Metab. 77 (Suppl 2):S28–S35. 2021.PubMed/NCBI View Article : Google Scholar
25	Brudek T: Inflammatory bowel diseases and Parkinson's diseases. J Parkinsons Dis. 9(s2):S331–S344. 2019.PubMed/NCBI View Article : Google Scholar
26	Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB and Keshavarzian A: Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease', PLoS. One. 6(e28032)2011.PubMed/NCBI View Article : Google Scholar
27	Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G, Quraishi MN, Kinross J, Smidt H, Tuohy KM, et al: The gut microbiota and host health: A new clinical frontier. Gut. 65:330–339. 2016.PubMed/NCBI View Article : Google Scholar
28	Rocha Cabrero F and Morrison EH: Lewy Bodies. In: StatPearls. StatPearls Publishing, Treasure Island, FL, 2025.
29	Jia X, Wang Q, Liu M and Ding J: The interplay between gut microbiota and the brain-gut axis in Parkinson's disease treatment. Front Neurol. 15(1415463)2024.PubMed/NCBI View Article : Google Scholar
30	Gorecki AM, Preskey L, Bakeberg MC, Kenna JE, Gildenhuys C, MacDougall G, Dunlop SA, Mastaglia FL, Akkari PA, Koengten F and 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. 13(839)2019.PubMed/NCBI View Article : Google Scholar
31	Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, et al: Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord. 30:350–358. 2015.PubMed/NCBI View Article : Google Scholar
32	Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R and Soleimanpour S: A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin Microbiol Rev. 35(e0033820)2022.PubMed/NCBI View Article : Google Scholar
33	Keshavarzian A, Green SJ, Engen PA, Voigt RM, Naqib A, Forsyth CB, Mutlu E and Shannon KM: Colonic bacterial composition in Parkinson's disease. Mov Disord. 30:1351–1360. 2015.PubMed/NCBI View Article : Google Scholar
34	Heintz-Buschart A and Wilmes P: Human gut microbiome: Function matters. Trends Microbiol. 26:563–574. 2018.PubMed/NCBI View Article : Google Scholar
35	Hill-Burns EM, Debelius JW, Morton JT, Wissemann WT, Lewis MR, Wallen ZD, Peddada SD, Factor SA, Molho E, Zabetian CP, et al: Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome. Mov Disord. 32:739–749. 2017.PubMed/NCBI View Article : Google Scholar
36	Perez-Pardo P, Kliest T, Dodiya HB, Broersen LM, Garssen J, Keshavarzian A and Kraneveld AD: . The gut-brain axis in Parkinson's disease: Possibilities for food-based therapies. Eur J Pharmacol. 817:86–95. 2017.PubMed/NCBI View Article : Google Scholar
37	Shi J, Wang Y, Chen D, Xu X, Li W, Li K, He J, Su W and Luo Q: The alteration of intestinal mucosal α-synuclein expression and mucosal microbiota in Parkinson's disease. Appl Microbiol Biotechnol. 107:1917–1929. 2023.PubMed/NCBI View Article : Google Scholar
38	Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, et al: Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 167:1469–1480.e12. 2016.PubMed/NCBI View Article : Google Scholar
39	Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, Faßbender K, Schwiertz A and Schäfer KH: Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord. 32:66–72. 2016.PubMed/NCBI View Article : Google Scholar
40	Cirstea MS, Yu AC, Golz E, Sundvick K, Kliger D, Radisavljevic N, Foulger LH, Mackenzie M, Huan T, Finlay BB and Appel-Cresswell S: Microbiota composition and metabolism are associated with gut function in Parkinson's disease. Mov Disord. 35:1208–1217. 2020.PubMed/NCBI View Article : Google Scholar
41	Keshavarzian A, Engen P, Bonvegna S and Cilia R: The gut microbiome in Parkinson's disease: A culprit or a bystander? Prog Brain Res. 252:357–450. 2020.PubMed/NCBI View Article : Google Scholar
42	Murros KE, Huynh VA, Takala TM and Saris PEJ: Desulfovibrio bacteria are associated with Parkinson's disease. Front Cell Infect Microbiol. 11(652617)2021.PubMed/NCBI View Article : Google Scholar
43	Qian Y, Yang X, Xu S, Wu C, Song Y, Qin N, Chen SD and Xiao Q: Alteration of the fecal microbiota in Chinese patients with Parkinson's disease. Brain Behav Immun. 70:194–202. 2018.PubMed/NCBI View Article : Google Scholar
44	Vascellari S, Melis M, Palmas V, Pisanu S, Serra A, Perra D, Santoru ML, Oppo V, Cusano R, Uva P, et al: Clinical phenotypes of Parkinson's disease associate with distinct gut microbiota and metabolome enterotypes. Biomolecules. 11(144)2021.PubMed/NCBI View Article : Google Scholar
45	Ashique S, Mohanto S, Ahmed MG, Mishra N, Garg A, Chellappan DK, Omara T, Iqbal S and Kahwa I: Gut-brain axis: A cutting-edge approach to target neurological disorders and potential synbiotic application. Heliyon. 10(e34092)2024.PubMed/NCBI View Article : Google Scholar
46	Barichella M, Severgnini M, Cilia R, Cassani E, Bolliri C, Caronni S, Ferri V, Cancello R, Ceccarani C, Faierman S, et al: Unraveling gut microbiota in Parkinson's disease and atypical parkinsonism. Mov Disord. 34:396–405. 2019.PubMed/NCBI View Article : Google Scholar
47	Lubomski M, Davis RL and Sue CM: The gut microbiota: A novel therapeutic target in Parkinson's disease? Parkinsonism Relat Disord. 66:265–266. 2019.PubMed/NCBI View Article : Google Scholar
48	Suresh SB, Malireddi A, Abera M, Noor K, Ansar M, Boddeti S and Nath TS: Gut microbiome and its role in Parkinson's disease. Cureus. 16(e73150)2024.PubMed/NCBI View Article : Google Scholar
49	Ambrosini YM, Borcherding D, Kanthasamy A, Kim HJ, Willette AA, Jergens A, Allenspach K and Mochel JP: The gut-brain axis in neurodegenerative diseases and relevance of the canine model: A review. Front Aging Neurosci. 11(130)2019.PubMed/NCBI View Article : Google Scholar
50	Zhang X, Tang B and Guo J: Parkinson's disease and gut microbiota: From clinical to mechanistic and therapeutic studies. Transl Neurodegener. 12(59)2023.PubMed/NCBI View Article : Google Scholar
51	Kleine Bardenhorst S, Cereda E, Severgnini M, Barichella M, Pezzoli G, Keshavarzian A, Desideri A, Pietrucci D, Aho VTE, Scheperjans F, et al: Gut microbiota dysbiosis in Parkinson disease: A systematic review and pooled analysis. Eur J Neurol. 30:3581–3594. 2023.PubMed/NCBI View Article : Google Scholar
52	Chandrasekaran P, Weiskirchen S and Weiskirchen R: Effects of probiotics on gut microbiota: An overview. Int J Mol Sci. 25(6022)2024.PubMed/NCBI View Article : Google Scholar
53	Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR and Scaldaferri F: Gut microbiota, intestinal permeability, and systemic inflammation: A narrative review. Intern Emerg Med. 19:275–293. 2024.PubMed/NCBI View Article : Google Scholar
54	Tzour A, Leibovich H, Barkai O, Biala Y, Lev S, Yaari Y and Binshtok AM: K_V 7/M channels as targets for lipopolysaccharide-induced inflammatory neuronal hyperexcitability. J Physiol. 595:713–738. 2017.PubMed/NCBI View Article : Google Scholar
55	Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE and Lang AE: Parkinson disease. Nat Rev Dis Primers. 3(17013)2017.PubMed/NCBI View Article : Google Scholar
56	Tan AH, Lim SY, Chong KK, Manap MAA, Hor JW, Lim JL, Low SC, Chong CW, Mahadeva S and Lang AE: Probiotics for constipation in Parkinson Disease: A Randomized Placebo-Controlled Study. Neurology. 96:e772–e782. 2021.PubMed/NCBI View Article : Google Scholar
57	Martin CR, Osadchiy V, Kalani A and Mayer EA: The brain-gut-microbiome axis. Cell Mol Gastroenterol Hepatol. 6:133–148. 2018.PubMed/NCBI View Article : Google Scholar
58	Segal A, Zlotnik Y, Moyal-Atias K, Abuhasira R and Ifergane G: Fecal microbiota transplant as a potential treatment for Parkinson's disease-A case series. Clin Neurol Neurosurg. 207(106791)2021.PubMed/NCBI View Article : Google Scholar
59	DuPont HL, Suescun J, Jiang ZD, Brown EL, Essigmann HT, Alexander AS, DuPont AW, Iqbal T, Utay NS, Newmark M and Schiess MC: Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study. Front Neurol. 14(1104759)2023.PubMed/NCBI View Article : Google Scholar
60	Xue LJ, Yang XZ, Tong Q, Shen P, Ma SJ, Wu SN, Zheng JL and Wang HG: Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study. Medicine (Baltimore). 99(e22035)2020.PubMed/NCBI View Article : Google Scholar
61	Westfall S, Lomis N, Kahouli I, Dia SY, Singh SP and Prakash S: Microbiome, probiotics and neurodegenerative diseases: Deciphering the gut brain axis. Cell Mol Life Sci. 74:3769–3787. 2017.PubMed/NCBI View Article : Google Scholar
62	Warren A, Nyavor Y, Zarabian N, Mahoney A and Frame LA: The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: A narrative review of the emerging literature. Front Immunol. 15(1365673)2024.PubMed/NCBI View Article : Google Scholar
63	Gupta R, Kumari S, Senapati A, Ambasta RK and Kumar P: New era of artificial intelligence and machine learning-based detection, diagnosis, and therapeutics in Parkinson's disease. Ageing Res Rev. 90(102013)2023.PubMed/NCBI View Article : Google Scholar
64	Palacios N, Wilkinson J, Bjornevik K, Schwarzschild MA, McIver L, Ascherio A and Huttenhower C: Metagenomics of the gut microbiome in Parkinson's disease: Prodromal changes. Ann Neurol. 94:486–501. 2023.PubMed/NCBI View Article : Google Scholar
65	Hey G, Nair N, Klann E, Gurrala A, Safarpour D, Mai V, Ramirez-Zamora A and Vedam-Mai V: Therapies for Parkinson's disease and the gut microbiome: Evidence for bidirectional connection. Front Aging Neurosci. 15(1151850)2023.PubMed/NCBI View Article : Google Scholar
66	Arnold JW, Roach J and Azcarate-Peril MA: Emerging technologies for gut microbiome research. Trends Microbiol. 24:887–901. 2016.PubMed/NCBI View Article : Google Scholar