Advanced research in health science has broadened our view in approaching and understanding the pathophysiology of diseases and has also revolutionised diagnosis and treatment. Ever since the establishment of Braak's hypothesis in the propagation of alpha-synuclein from the distant olfactory and enteric nervous system towards the brain in Parkinson's Disease (PD), studies have explored and revealed the involvement of altered gut microbiota in PD. This review recapitulates the gut microbiome associated with PD severity, duration, motor and non-motor symptoms, and antiparkinsonian treatment from recent literature. Gut microbial signatures in PD are potential predictors of the disease and are speculated to be used in early diagnosis and treatment. In brief, the review also emphasises on implications of the prebiotic, probiotic, faecal microbiota transplantation, and dietary interventions as alternative treatments in modulating the disease symptoms in PD.

Department of Medicine University of Cambridge Cambridge UK

Department of Neurology Bharati Vidyapeeth Medical College and Hospital Pune India

Department of Neurology Kasturba Medical College Manipal Academy of Higher Education Manipal India

Enteric Diseases Division Department of Microbiology Kasturba Medical College Manipal Academy of Higher Education Manipal Karnataka India

Molecular Genetics Laboratory Centre for Human Microbial Ecology Translational Health Sciences and Technology Institute NCR Biotech Science Cluster Faridabad India

National Institute of Cholera and Enteric Diseases Kolkata India

Zobrazit více v PubMed

Aho VTE, Pereira PAB, Voutilainen S, et al. Gut microbiota in Parkinson’s disease: Temporal stability and relations to disease progression. EBioMedicine. 2019;44:691–707. doi: 10.1016/j.ebiom.2019.05.064. PubMed DOI PMC

Al-Asmakh M, Hedin L. Microbiota and the control of blood-tissue barriers. Tissue Barriers. 2015;3:e1039691. doi: 10.1080/21688370.2015.1039691. PubMed DOI PMC

Baldini F, Hertel J, Sandt E, et al. Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions. BMC Biol. 2020;18:62. doi: 10.1186/s12915-020-00775-7. PubMed DOI PMC

Barichella M, Pacchetti C, Bolliri C, et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease. Neurology. 2016;87:1274–1280. doi: 10.1212/WNL.0000000000003127. PubMed DOI

Barichella M, Severgnini M, Cilia R, et al. Unraveling gut microbiota in Parkinson’s disease and atypical parkinsonism. Mov Disord. 2019;34:396–405. doi: 10.1002/mds.27581. PubMed DOI

Beach TG, Adler CH, Sue LI, et al. Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol. 2010;119:689–702. doi: 10.1007/s00401-010-0664-3. PubMed DOI PMC

Becker A, Pierre Schmartz G, Gröger L et al (2021) Effects of Resistant Starch on Symptoms, Fecal Markers and Gut Microbiota in Parkinson’s Disease – the RESISTA-PD Trial. Genomics Proteomics Bioinformatics S1672–0229(21)00245-X. 10.1016/j.gpb.2021.08.009 PubMed PMC

Belzer C, Chia LW, Aalvink S et al (2017) Microbial Metabolic Networks at the Mucus Layer Lead to Diet-Independent Butyrate and Vitamin B 12 Production by Intestinal Symbionts. mBio 8:e00770–17. 10.1128/mBio.00770-17 PubMed PMC

Bendor J, Logan T, Edwards RH. The Function of α-Synuclein. Neuron. 2013;79:1044–1066. doi: 10.1016/J.NEURON.2013.09.004. PubMed DOI PMC

Béraud D, Twomey M, Bloom B, et al. α-Synuclein Alters Toll-Like Receptor Expression. Front Neurosci. 2011;5:80. doi: 10.3389/fnins.2011.00080. PubMed DOI PMC

Bienenstock J, Kunze W, Forsythe P. Microbiota and the gut-brain axis. Nutr Rev. 2015;73:28–31. doi: 10.1093/nutrit/nuv019. PubMed DOI

Blesa J, Phani S, Jackson-Lewis V, Przedborski S. Classic and new animal models of Parkinson’s disease. J Biomed Biotechnol. 2012;2012:845618. doi: 10.1155/2012/845618. PubMed DOI PMC

Braniste V, Al-Asmakh M, Kowal C et al (2014) The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med 6:263ra158. 10.1126/scitranslmed.3009759 PubMed PMC

Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28:203–209. PubMed PMC

Cersosimo MG, Raina GB, Pecci C, et al. Gastrointestinal manifestations in Parkinson's disease: prevalence and occurrence before motor symptoms. J Neurol. 2013;260:1332–1338. doi: 10.1007/s00415-012-6801-2. PubMed DOI

Chen SG, Stribinskis V, Rane MJ, et al. Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans. Sci Rep. 2016;6:34477. doi: 10.1038/srep34477. PubMed DOI PMC

Cheng HC, Ulane CM, Burke RE. Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol. 2010;67:715–725. doi: 10.1002/ANA.21995. PubMed DOI PMC

Cirstea MS, Yu AC, Golz E, et al. Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson’s Disease. Mov Disord. 2020;35:1208–1217. doi: 10.1002/mds.28052. PubMed DOI

Cosma-Grigorov A, Meixner H, Mrochen A, et al. Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates. Front Neurol. 2020;11:1041. doi: 10.3389/fneur.2020.01041. PubMed DOI PMC

Couch Y, Alvarez-Erviti L, Sibson NR, et al. The acute inflammatory response to intranigral α-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation. J Neuroinflammation. 2011;8:166. doi: 10.1186/1742-2094-8-166. PubMed DOI PMC

David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–563. doi: 10.1038/nature12820. PubMed DOI PMC

De Filippis F, Pellegrini N, Vannini L, et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2016;65:1812–1821. doi: 10.1136/gutjnl-2015-309957. PubMed DOI

Derkinderen P, Shannon KM, Brundin P. Gut feelings about smoking and coffee in Parkinson’s disease. Mov Disord. 2014;29:976–979. doi: 10.1002/mds.25882. PubMed DOI PMC

Derrien M, Belzer C, de Vos WM. Akkermansia muciniphila and its role in regulating host functions. Microb Pathog. 2017;106:171–181. doi: 10.1016/j.micpath.2016.02.005. PubMed DOI

Devos D, Lebouvier T, Lardeux B, et al. Colonic inflammation in Parkinson’s disease. Neurobiol Dis. 2013;50:42–48. doi: 10.1016/j.nbd.2012.09.007. PubMed DOI

Dinan TG, Cryan JF. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J Physiol. 2017;595:489–503. doi: 10.1113/JP273106. PubMed DOI PMC

Erny D, De Angelis ALH, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18:965–977. doi: 10.1038/nn.4030. PubMed DOI PMC

Forsyth CB, Shannon KM, Kordower JH, et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS ONE. 2011;6:e28032. doi: 10.1371/journal.pone.0028032. PubMed DOI PMC

Freire C, Koifman S. Pesticide exposure and Parkinson’s disease: Epidemiological evidence of association. Neurotoxicology. 2012;33:947–971. doi: 10.1016/j.neuro.2012.05.011. PubMed DOI

Gatto NM, Cockburn M, Bronstein J, et al. Well-Water Consumption and Parkinson’s Disease in Rural California. Environ Health Perspect. 2009;117:1912. doi: 10.1289/ehp.0900852. PubMed DOI PMC

Georgescu D, Ancusa OE, Georgescu LA, et al. Nonmotor gastrointestinal disorders in older patients with Parkinson’s disease: is there hope? Clin Interv Aging. 2016;11:1601–1608. doi: 10.2147/CIA.S106284. PubMed DOI PMC

Goetz CG, Fahn S, Martinez-Martin P, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan. Mov Disord. 2007;22:41–47. doi: 10.1002/mds.21198. PubMed DOI

Goldman SM, Kamel F, Ross GW, et al. Peptidoglycan recognition protein genes and risk of Parkinson’s disease. Mov Disord. 2014;29:1171–1180. doi: 10.1002/mds.25895. PubMed DOI PMC

Gundert-Remy U, Hildebrandt R, Stiehl A, et al. Intestinal absorption of levodopa in man. Eur J Clin Pharmacol. 1983;25:69–72. doi: 10.1007/BF00544017. PubMed DOI

Mohajeri MH, La Fata G, Steinert RE, et al. Relationship between the gut microbiome and brain function. Nutr Rev. 2018;76:481–496. doi: 10.1093/nutrit/nuy009. PubMed DOI

Hasegawa S, Goto S, Tsuji H, et al. Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson’s disease. PLoS ONE. 2015;10:e0142164. doi: 10.1371/journal.pone.0142164. PubMed DOI PMC

Hegelmaier T, Lebbing M, Duscha A, et al. Interventional Influence of the Intestinal Microbiome Through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson’s Disease. Cells. 2020;9:376. doi: 10.3390/cells9020376. PubMed DOI PMC

Heiman ML, Greenway FL. A healthy gastrointestinal microbiome is dependent on dietary diversity. Mol Metab. 2016;5:317–320. doi: 10.1016/j.molmet.2016.02.005. PubMed DOI PMC

Heintz-Buschart A, Pandey U, Wicke T, et al. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord. 2018;33:88–98. doi: 10.1002/mds.27105. PubMed DOI PMC

Herrick MK, Tansey MG. Is LRRK2 the missing link between inflammatory bowel disease and Parkinson’s disease? NPJ Parkinsons Dis. 2021;7:26. doi: 10.1038/s41531-021-00170-1. PubMed DOI PMC

Hill-Burns EM, Debelius JW, Morton JT, et al. Parkinson’s Disease and Parkinson’s Disease Medications Have Distinct Signatures of the Gut Microbiome. Mov Disord. 2017;32:739–749. doi: 10.1002/mds.26942. PubMed DOI PMC

Holmqvist S, Chutna O, Bousset L, et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014;128:805–820. doi: 10.1007/s00401-014-1343-6. PubMed DOI

Horsager J, Andersen KB, Knudsen K, et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain. 2020;143:3077–3088. doi: 10.1093//brain/awaa238. PubMed DOI

Huang H, Xu H, Luo Q, et al. Fecal microbiota transplantation to treat Parkinson’s disease with constipation: A case report. Medicine (baltimore) 2019;98:e16163. doi: 10.1097/MD.0000000000016163. PubMed DOI PMC

Huuskonen J, Suuronen T, Nuutinen T et al (2004) Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids. Br J Pharmacol 141:874–880. 10.1038/sj.bjp.0705682 PubMed PMC

Ibrahim A, Raja Ali RA, Abdul Manaf MR, et al. Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson’s disease: A randomised controlled trial. PLoS ONE. 2020;15:e0244680. doi: 10.1371/journal.pone.0244680. PubMed DOI PMC

Jackson A, Forsyth CB, Shaikh M, et al. Diet in Parkinson’s Disease: Critical Role for the Microbiome. Front Neurol. 2019;10:1245. doi: 10.3389/fneur.2019.01245. PubMed DOI PMC

Jin M, Li J, Liu F, et al. Analysis of the Gut Microflora in Patients With Parkinson's Disease. Front Neurosci. 2019;13:1184. doi: 10.3389/fnins.2019.01184. PubMed DOI PMC

Jost WH, Reichmann H. "An essay on the shaking palsy" 200 years old. J Neural Transm (vienna) 2017;124:899–900. doi: 10.1007/s00702-017-1684-0. PubMed DOI

Kasper D, Fauci A, Hauser S, et al. Harrison’s Principles of Internal Medicine 19th edn (Vols 1+2) McGraw Hill; 2014.

Kaur R, Mehan S, Singh S. Understanding multifactorial architecture of Parkinson's disease: pathophysiology to management. Neurol Sci. 2019;40:13–23. doi: 10.1007/s10072-018-3585-x. PubMed DOI

Kaye J, Gage H, Kimber A, et al. Excess burden of constipation in Parkinson’s disease: a pilot study. Mov Disord. 2006;21:1270–1273. doi: 10.1002/mds.20942. PubMed DOI

Keshavarzian A, Green SJ, Engen PA, et al. Colonic bacterial composition in Parkinson's disease. Mov Disord. 2015;30:1351–1360. doi: 10.1002/mds.26307. PubMed DOI

Kim JS, Sung HY (2015) Gastrointestinal Autonomic Dysfunction in Patients with Parkinson’s Disease. J Mov Disord 8:76–82. 10.14802/jmd.15008 PubMed PMC

Klünemann M, Andrejev S, Blasche S, et al. Bioaccumulation of therapeutic drugs by human gut bacteria. Nature. 2021;597:533–538. doi: 10.1038/s41586-021-03891-8. PubMed DOI PMC

Kuai XY, Yao XH, Xu LJ, et al. Evaluation of fecal microbiota transplantation in Parkinson’s disease patients with constipation. Microb Cell Fact. 2021;20:98. doi: 10.1186/s12934-021-01589-0. PubMed DOI PMC

Lee E-J, Woo M-S, Moon P-G, et al. Alpha-synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1. J Immunol. 2010;185:615–623. doi: 10.4049/jimmunol.0903480. PubMed DOI

Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124:837–848. doi: 10.1016/j.cell.2006.02.017. PubMed DOI

Li W, Wu X, Hu X, et al. Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features. Sci China Life Sci. 2017;60:1223–1233. doi: 10.1007/s11427-016-9001-4. PubMed DOI

Lin A, Zheng W, He Y, et al. Gut microbiota in patients with Parkinson’s disease in southern China. Parkinsonism Relat Disord. 2018;53:82–88. doi: 10.1016/j.parkreldis.2018.05.007. PubMed DOI

Lin CH, Chen CC, Chiang HL, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. J Neuroinflammation. 2019;16:129. doi: 10.1186/s12974-019-1528-y. PubMed DOI PMC

Liu S, Da Cunha AP, Rezende RM, et al. The Host Shapes the Gut Microbiota via Fecal MicroRNA. Cell Host Microbe. 2016;19:32–43. doi: 10.1016/j.chom.2015.12.005. PubMed DOI PMC

Lolekha P, Sriphanom T, Vilaichone R-K (2021) Helicobacter pylori eradication improves motor fluctuations in advanced Parkinson’s disease patients: A prospective cohort study (HP-PD trial). PLoS One 16:e0251042. 10.1371/journal.pone.0251042 PubMed PMC

Lubomski M, Xu X, Holmes AJ, et al. The impact of device-assisted therapies on the gut microbiome in Parkinson’s disease. J Neurol. 2021;269:780–795. doi: 10.1007/s00415-021-10657-9. PubMed DOI

Luna E, Luk KC. Bent out of shape: α-Synuclein misfolding and the convergence of pathogenic pathways in Parkinson’s disease. FEBS Lett. 2015;589:3749–3759. doi: 10.1016/J.FEBSLET.2015.10.023. PubMed DOI PMC

Maraki MI, Yannakoulia M, Stamelou M, et al. Mediterranean diet adherence is related to reduced probability of prodromal Parkinson’s disease. Mov Disord. 2019;34:48–57. doi: 10.1002/mds.27489. PubMed DOI

Martínez I, Lattimer JM, Hubach KL, et al. Gut microbiome composition is linked to whole grain-induced immunological improvements Subject Category: microbe-microbe and microbe-host interactions. ISME J. 2013;7:269–280. doi: 10.1038/ismej.2012.104. PubMed DOI PMC

Massier L, Blüher M, Kovacs P, Chakaroun RM. Impaired Intestinal Barrier and Tissue Bacteria: Pathomechanisms for Metabolic Diseases. Front Endocrinol (lausanne) 2021;12:616506. doi: 10.3389/fendo.2021.616506. PubMed DOI PMC

Matheoud D, Cannon T, Voisin A, et al. Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1 −/− mice. Nature. 2019;571:565–569. doi: 10.1038/s41586-019-1405-y. PubMed DOI

Meade RM, Fairlie DP, Mason JM. Alpha-synuclein structure and Parkinson’s disease – lessons and emerging principles. Mol Neurodegener. 2019;14:1–14. doi: 10.1186/S13024-019-0329-1. PubMed DOI PMC

Melis M, Vascellari S, Santoru ML, et al. Gut microbiota and metabolome distinctive features in Parkinson disease: Focus on levodopa and levodopa-carbidopa intrajejunal gel. Eur J Neurol. 2021;28:1198–1209. doi: 10.1111/ene.14644. PubMed DOI

Merenstein D, El-Nachef N, Lynch SV. Fecal Microbial Therapy – Promises and Pitfalls. J Pediatr Gastroenterol Nutr. 2014;59:157–161. doi: 10.1097/MPG.0000000000000415. PubMed DOI PMC

Metcalfe-Roach A, Yu AC, Golz E, et al. MIND and Mediterranean Diets Associated with Later Onset of Parkinson’s Disease. Mov Disord. 2021;36:977–984. doi: 10.1002/mds.28464. PubMed DOI PMC

Molsberry S, Bjornevik K, Hughes KC, et al. Diet pattern and prodromal features of Parkinson disease. Neurology. 2020;95:e2095–e2108. doi: 10.1212/WNL.0000000000010523. PubMed DOI PMC

Moons R, Konijnenberg A, Mensch C, et al. Metal Ions Shape α-Synuclein Sci Rep. 2020;10:1–13. doi: 10.1038/s41598-020-73207-9. PubMed DOI PMC

Mulak A. A controversy on the role of short-chain fatty acids in the pathogenesis of Parkinson’s disease. Mov Disord. 2018;33:398–401. doi: 10.1002/MDS.27304. PubMed DOI

Mulak A, Koszewicz M, Panek-Jeziorna M, et al. Fecal calprotectin as a marker of the gut immune system activation is elevated in parkinson’s disease. Front Neurosci. 2019;13:992. doi: 10.3389/fnins.2019.00992. PubMed DOI PMC

NIH Human Microbiome Project defines normal bacterial makeup of the body | National Institutes of Health (NIH) (2012) News Release-June13, 2012. https://www.nih.gov/news-events/news-releases/nih-human-microbiome-project-defines-normal-bacterial-makeup-body. Accessed 5 Apr 2022

Nishiwaki H, Ito M, Ishida T, et al. Meta-Analysis of Gut Dysbiosis in Parkinson’s Disease. Mov Disord. 2020;35:1626–1635. doi: 10.1002/mds.28119. PubMed DOI

Oliphant K, Allen-Vercoe E. Macronutrient metabolism by the human gut microbiome: Major fermentation by-products and their impact on host health. Microbiome. 2019;7:91. doi: 10.1186/s40168-019-0704-8. PubMed DOI PMC

Pan-Montojo F, Schwarz M, Winkler C, et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep. 2012;2:898. doi: 10.1038/srep00898. PubMed DOI PMC

Pang SY, Ho PW, Liu HF, et al. The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson's disease. Transl Neurodegener. 2019;8:23. doi: 10.1186/S40035-019-0165-9. PubMed DOI PMC

Parkinson J. An essay on the shaking palsy. 1817 (2002) . J Neuropsychiatry Clin Neurosci 14:223–222. 10.1176/jnp.14.2.223 PubMed

Pierantozzi M, Pietroiusti A, Brusa L, et al. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology. 2006;66:1824–1829. doi: 10.1212/01.wnl.0000221672.01272.ba. PubMed DOI

Pietrucci D, Cerroni R, Unida V, et al. Dysbiosis of gut microbiota in a selected population of Parkinson’s patients. Parkinsonism Relat Disord. 2019;65:124–130. doi: 10.1016/j.parkreldis.2019.06.003. PubMed DOI

Poewe W. Non-motor symptoms in Parkinson's disease. Eur J Neurol. 2008;15(Suppl 1):14–20. doi: 10.1111/j.1468-1331.2008.02056.x. PubMed DOI

Qian Y, Yang X, Xu S, et al. Alteration of the fecal microbiota in Chinese patients with Parkinson’s disease. Brain Behav Immun. 2018;70:194–202. doi: 10.1016/j.bbi.2018.02.016. PubMed DOI

Rekdal VM, Bess EN, Bisanz JE et al (2019) Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science 364:eaau6323. 10.1126/science.aau6323 PubMed PMC

Ren T, Gao Y, Qiu Y, et al. Gut Microbiota Altered in Mild Cognitive Impairment Compared With Normal Cognition in Sporadic Parkinson’s Disease. Front Neurol. 2020;11:137. doi: 10.3389/fneur.2020.00137. PubMed DOI PMC

Riess O, Krüger R. J Neural Transm Suppl. 1999;56:113–125. doi: 10.1007/978-3-7091-6360-3_6. PubMed DOI

Scheperjans F, Aho V, Pereira PA, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord. 2015;30:350–358. doi: 10.1002/mds.26069. PubMed DOI

Schwiertz A, Spiegel J, Dillmann U, et al. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson’s disease. Parkinsonism Relat Disord. 2018;50:104–107. doi: 10.1016/j.parkreldis.2018.02.022. PubMed DOI

Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016;14:e1002533. doi: 10.1371/journal.pbio.1002533. PubMed DOI PMC

Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease—an evidence-based medicine review. Mov Disord. 2019;34:180–198. doi: 10.1002/mds.27602. PubMed DOI PMC

Sikander A, Rana SV, Prasad KK. Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta. 2009;403:47–55. doi: 10.1016/j.cca.2009.01.028. PubMed DOI

Silverman MS, Davis I, Pillai DR. Success of Self-Administered Home Fecal Transplantation for Chronic Clostridium difficile Infection. Clin Gastroenterol Hepatol. 2010;8:471–473. doi: 10.1016/j.cgh.2010.01.007. PubMed DOI

Statistics | Parkinson’s Foundation (2021) https://www.parkinson.org/Understanding-Parkinsons/Statistics. Accessed 26 Oct 2021

Stefanis L. α-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med. 2012;2:1–23. doi: 10.1101/cshperspect.a009399. PubMed DOI PMC

Stolzenberg E, Berry D, Yang D, et al. A Role for Neuronal Alpha-Synuclein in Gastrointestinal Immunity. J Innate Immun. 2017;9:456–463. doi: 10.1159/000477990. PubMed DOI PMC

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. PubMed DOI

Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R, et al. Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2019;38:1031–1035. doi: 10.1016/j.clnu.2018.05.018. PubMed DOI

Tan AH, Lim S-Y, Mahadeva S, et al. Helicobacter pylori Eradication in Parkinson’s Disease: A Randomized Placebo-Controlled Trial. Mov Disord. 2020;35:2250–2260. doi: 10.1002/MDS.28248. PubMed DOI

Tan AH, Lim SY, Chong KK, et al. Probiotics for Constipation in Parkinson Disease: A Randomized Placebo-Controlled Study. Neurology. 2021;96:e772–e782. doi: 10.1212/WNL.0000000000010998. PubMed DOI

Tan AH, Mahadeva S, Marras C, et al. Helicobacter pylori infection is associated with worse severity of Parkinson’s disease. Parkinsonism Relat Disord. 2014;21:221–225. doi: 10.1016/j.parkreldis.2014.12.009. PubMed DOI

Unger MM, Spiegel J, Dillmann KU, et al. 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. PubMed DOI

Van Kessel SP, de Jong HR, Winkel SL, et al. Gut bacterial deamination of residual levodopa medication for Parkinson’s disease. BMC Biol. 2020;18:137. doi: 10.1186/s12915-020-00876-3. PubMed DOI PMC

Van Kessel SP, Frye AK, El-Gendy AO, et al. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease. Nat Commun. 2019;10:310. doi: 10.1038/S41467-019-08294-Y. PubMed DOI PMC

Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017;11:821–824. doi: 10.1080/17474124.2017.1343143. PubMed DOI PMC

Vidal-martinez G, Chin B, Camarillo C, et al. 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. 2020;10:185–192. doi: 10.3233/JPD-191693. PubMed DOI PMC

Wallen ZD, Appah M, Dean MN, et al. Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens. NPJ Parkinsons Dis. 2020;6:11. doi: 10.1038/s41531-020-0112-6. PubMed DOI PMC

Wallen ZD, Stone WJ, Factor SA, et al. Exploring human-genome gut-microbiome interaction in Parkinson’s disease. NPJ Parkinsons Dis. 2021;7:74. doi: 10.1038/s41531-021-00218-2. PubMed DOI PMC

Weis S, Schwiertz A, Unger MM, et al. Effect of Parkinson’s disease and related medications on the composition of the fecal bacterial microbiota. NPJ Parkinsons Dis. 2019;5:28. doi: 10.1038/s41531-019-0100-x. PubMed DOI PMC

Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–108. doi: 10.1126/science.1208344. PubMed DOI PMC

Xue LJ, Yang XZ, Tong Q, et al. Fecal microbiota transplantation therapy for Parkinson’s disease: A preliminary study. Medicine (baltimore) 2020;99:e22035. doi: 10.1097/MD.0000000000022035. PubMed DOI PMC

Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–276. doi: 10.1016/j.cell.2015.02.047. PubMed DOI PMC

Zhao Y, Yu YB. Intestinal Microbiota and Chronic Constipation Springerplus. 2016;5:1130. doi: 10.1186/S40064-016-2821-1. PubMed DOI PMC

Zhu F, Li C, Gong J, et al. The risk of Parkinson’s disease in inflammatory bowel disease: A systematic review and meta-analysis. Dig Liver Dis. 2019;51:38–42. doi: 10.1016/J.DLD.2018.09.017. PubMed DOI