Skip to main content

Advertisement

SpringerLink
Log in

Gut brain axis: an insight into microbiota role in Parkinson’s disease

  • Review Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. It is characterized neuropathologically by the presence of alpha-synuclein containing Lewy Bodies in the substantia nigra of the brain with loss of dopaminergic neurons in the pars compacta of the substantia nigra. The presence of alpha-synuclein aggregates in the substantia nigra and the enteric nervous system (ENS) drew attention to the possibility of a correlation between the gut microbiota and Parkinson’s disease. The gut-brain axis is a two-way communication system, which explains how through the vagus nerve, the gut microbiota can affect the central nervous system (CNS), including brain functions related to the ENS, as well as how CNS can alter various gut secretions and immune responses. As a result, this dysbiosis or alteration in gut microbiota can be an early sign of PD with reported changes in short chain fatty acids, bile acids, and lipids. This gave rise to the use of probiotics and faecal microbiota transplantation as alternative approaches to improve the symptoms of patients with PD. The aim of this review is to discuss investigations that have been done to explore the gastrointestinal involvement in Parkinson’s disease, the effect of dysbiosis, and potential therapeutic strategies for PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Aho VTE, Pereira PAB, 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Alecu I, Bennett SAL (2019) 'Dysregulated lipid metabolism and its role in α-synucleinopathy in Parkinson’s disease. Front Neurosci 13(328)

  • Ascherio A, Schwarzschild MA (2016) The epidemiology of Parkinson's disease: risk factors and prevention. Lancet Neurol 15(12):1257–1272. https://doi.org/10.1016/S1474-4422(16)30230-7

  • Baizabal-Carvallo J (2021) Gut microbiota: a potential therapeutic target for Parkinsons disease. Neural Regen Res 16(2):287. https://doi.org/10.4103/1673-5374.290896

    Article  PubMed  Google Scholar 

  • Barry TJ, Murray L, Fearon P, Moutsiana C, Johnstone T, Halligan SL (2017) Amygdala volume and hypothalamic-pituitary-adrenal axis reactivity to social stress. Psychoneuroendocrinology 85:96–99

    Article  PubMed  PubMed Central  Google Scholar 

  • Beitz JM (2014) Parkinson’s disease: a review. Front Biosci (schol Ed) 6:65–74

    Article  Google Scholar 

  • Bellou V, Belbasis L, Tzoulaki I, Evangelou E, Ioannidis JP (2016) Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses. Parkinsonism Relat Disord 23:1–9

  • Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211

    Article  PubMed  Google Scholar 

  • Britannica TE (2018) Digestive nerve plexus

  • Butterworth AD, Thomas AG, Akobeng AK (2008) Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2008(3):CD006634-CD006634

  • Cammarota G, Pecere S, Ianiro G, Masucci L, Currò D (2016) Principles of DNA-based gut microbiota assessment and therapeutic efficacy of fecal microbiota transplantation in gastrointestinal diseases. Dig Dis 34(3):279–285

    Article  PubMed  Google Scholar 

  • Cassani E, Privitera G, Pezzoli G, Pusani C, Madio C, Iorio L, Barichella M (2011) Use of probiotics for the treatment of constipation in Parkinson’s disease patients. Minerva Gastroenterol Dietol 57(2):117–121

    CAS  PubMed  Google Scholar 

  • Chen Z-J, Liang C-Y, Yang L-Q, Ren S-M, Xia Y-M, Cui L et al (2021) Association of Parkinson’s disease with microbes and microbiological therapy. Front Cell Infect Microbiol. https://doi.org/10.3389/fcimb.2021.619354

    Article  PubMed  PubMed Central  Google Scholar 

  • Cirstea MS, Yu AC, Golz E, Sundvick K, Kliger D, Radisavljevic N, Foulger LH, Mackenzie M, Huan T, Finlay BB, Appel-Cresswell S (2020) Microbiota composition and metabolism are associated with gut function in Parkinson’s disease. Mov Disord 35(7):1208–1217

    Article  CAS  PubMed  Google Scholar 

  • Costa M, Brookes SJ, Hennig GW (2000) Anatomy and physiology of the enteric nervous system. Gut 47 (Suppl 4):iv15–iv26

  • Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13(10):701–712. https://doi.org/10.1038/nrn3346

    Article  CAS  PubMed  Google Scholar 

  • Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, Berenjian A, Ghasemi Y (2019) Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods 8(3):92

  • Dobbs SM, Dobbs RJ, Weller C, Charlett A, Bjarnason IT, Lawson AJ, Letley D, Harbin L, Price AB, Ibrahim MA, Oxlade NL, Bowthorpe J, Leckstroem D, Smee C, Plant JM, Peterson DW (2010) Differential effect of Helicobacter pylori eradication on time-trends in brady/hypokinesia and rigidity in idiopathic parkinsonism. Helicobacter 15(4):279–294

    Article  PubMed  PubMed Central  Google Scholar 

  • Doroftei B, Ilie OD, Cojocariu RO, Ciobica A, Maftei R, Grab D, Anton E, McKenna J, Dhunna N, Simionescu G (2020) Minireview exploring the biological cycle of vitamin B3 and its influence on oxidative stress: further molecular and clinical aspects. Molecules 25(15)

  • Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR et al (2001) Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinsons disease. Proc Natl Acad Sci 98(25):14669–14674. https://doi.org/10.1073/pnas.251341998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dutta SK, Verma S, Jain V, Surapaneni BK, Vinayek R, Phillips L, Nair PP (2019) Parkinson’s disease: the emerging role of gut dysbiosis, antibiotics, probiotics, and fecal microbiota transplantation. J Neurogastroenterol Motil 25(3):363–376

    Article  PubMed  PubMed Central  Google Scholar 

  • Elfil M, Kamel S, Kandil M, Koo BB, Schaefer SM (2020) Implications of the gut microbiome in Parkinson’s disease. Mov Disord 35(6):921–933

    Article  CAS  PubMed  Google Scholar 

  • Fang X (2019) Microbial treatment: the potential application for Parkinson’s disease. Neurol Sci off J Ital Neurol Soc Ital Soc Clin Neurophysiol 40(1):51–58

    Google Scholar 

  • Fanning S, Selkoe D, Dettmer U (2020) Parkinson’s disease: proteinopathy or lipidopathy? NPJ Parkinsons Dis 6:3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fasano A, Bove F, Gabrielli M, Petracca M, Zocco MA, Ragazzoni E, Barbaro F, Piano C, Fortuna S, Tortora A, Di Giacopo R, Campanale M, Gigante G, Lauritano EC, Navarra P, Marconi S, Gasbarrini A, Bentivoglio AR (2013) The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord 28(9):1241–1249

    Article  CAS  PubMed  Google Scholar 

  • Fields CT, Sampson TR, Bruce-Keller AJ, Kiraly DD, Hsiao EY, de Vries GJ (2018) Defining dysbiosis in disorders of movement and motivation. J Neurosci 38(44):9414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

  • Furness JB, Callaghan BP, Rivera LR, Cho HJ (2014) The enteric nervous system and gastrointestinal innervation: integrated local and central control. Adv Exp Med Biol 817:39–71

    Article  PubMed  Google Scholar 

  • Gazerani P (2019) Probiotics for Parkinson’s disease. Int J Mol Sci 20(17):4121

    Article  CAS  PubMed Central  Google Scholar 

  • Georgescu D, Ancusa OE, Georgescu LA, Ionita I, Reisz D (2016) Nonmotor gastrointestinal disorders in older patients with Parkinson’s disease: is there hope? Clin Interv Aging 11:1601–1608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Getz SJ, Levin B (2017) Cognitive and neuropsychiatric features of early Parkinson’s disease. Arch Clin Neuropsychol 32(7):769–785

    Article  PubMed  Google Scholar 

  • Goedert M, Masuda-Suzukake M, Falcon B (2017) Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration. Brain 140(2):266–278

    Article  PubMed  Google Scholar 

  • González-Lizárraga F, Socías SB, Ávila CL, Torres-Bugeau CM, Barbosa LR, Binolfi A, Sepúlveda-Díaz JE, Del-Bel E, Fernandez CO, Papy-Garcia D, Itri R, Raisman-Vozari R, Chehín RN (2017) Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species. Sci Rep 7:41755. https://doi.org/10.1038/srep41755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Graham SF, Rey NL, Ugur Z, Yilmaz A, Sherman E, Maddens M, Bahado-Singh RO, Becker K, Schulz E, Meyerdirk LK, Steiner JA, Ma J, Brundin P (2018) Metabolomic profiling of bile acids in an experimental model of prodromal parkinson’s disease. Metabolites 8(4):71

    Article  PubMed Central  CAS  Google Scholar 

  • Hasegawa S, Goto S, Tsuji H, Okuno T, Asahara T, Nomoto K, Shibata A, Fujisawa Y, Minato T, Okamoto A, Ohno K, Hirayama M (2015) Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in parkinson’s disease. PLOS ONE 10(11):e0142164

  • Hasuike Y, Endo T, Koroyasu M, Matsui M, Mori C, Yamadera M, Fujimura H, Sakoda S (2020) Bile acid abnormality induced by intestinal dysbiosis might explain lipid metabolism in Parkinson's disease. Med Hypotheses 134:109436

  • Heintz-Buschart A, Pandey U, Wicke T, Sixel-Döring F, Janzen A, Sittig-Wiegand E, Trenkwalder C, Oertel WH, Mollenhauer B, Wilmes P (2018) The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord 33(1):88–98

  • Hill-Burns EM, Debelius JW, Morton JT, Wissemann WT, Lewis MR, Wallen ZD, Peddada SD, Factor SA, Molho E, Zabetian CP, Knight R, Payami H (2017) Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome. Mov Disord 32(5):739–749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME (2014) The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11(8):506–514

    Article  PubMed  Google Scholar 

  • Hilton D, Stephens M, Kirk L, Edwards P, Potter R, Zajicek J, Broughton E, Hagan H, Carroll C (2014) Accumulation of α-synuclein in the bowel of patients in the pre-clinical phase of Parkinson’s disease. Acta Neuropathol 127(2):235–241

    Article  CAS  PubMed  Google Scholar 

  • Hopfner F, Künstner A, Müller SH, Künzel S, Zeuner KE, Margraf NG, Deuschl G, Baines JF, Kuhlenbäumer G (2017) Gut microbiota in Parkinson disease in a northern German cohort. Brain Res 1667:41–45

  • Hsieh TH, Kuo CW, Hsieh KH, Shieh MJ, Peng CW, Chen YC, Chang YL, Huang YZ, Chen CC, Chang PK, Chen KY, Chen HY (2020) Probiotics alleviate the progressive deterioration of motor functions in a mouse model of Parkinson's disease. Brain Sci 10(4)

  • Huang H, Xu H, Luo Q, He J, Li M, Chen H, Tang W, Nie Y, Zhou Y (2019) Fecal microbiota transplantation to treat Parkinson’s disease with constipation: a case report. Medicine 98(26):e16163–e16163

    Article  PubMed  PubMed Central  Google Scholar 

  • Hwang O (2013) Role of oxidative stress in Parkinson’s disease. Exp Neurobiol 22(1):11–17

    Article  PubMed  PubMed Central  Google Scholar 

  • Keshavarzian A, Green SJ, Engen PA, Voigt RM, Naqib A, Forsyth CB, Mutlu E, Shannon KM (2015) Colonic bacterial composition in Parkinson’s disease. Mov Disord 30(10):1351–1360

    Article  CAS  PubMed  Google Scholar 

  • Kilzheimer A, Hentrich T, Burkhardt S, Schulze-Hentrich JM (2019) The challenge and opportunity to diagnose Parkinson's disease in midlife. Front Neurol, 10(1328)

  • Kleinman M, Frank S (2013) Epidemiology and clinical diagnosis of Parkinson disease. PET Clin 8(4):447–458

    Article  PubMed  Google Scholar 

  • Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F (2016) From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165(6):1332–1345

    Article  CAS  PubMed  Google Scholar 

  • Konturek PC, Koziel J, Dieterich W, Haziri D, Wirtz S, Glowczyk I, Konturek K, Neurath MF, Zopf Y (2016) Successful therapy of Clostridium difficile infection with fecal microbiota transplantation. J Physiol Pharmacol 67(6):859–866

    CAS  PubMed  Google Scholar 

  • Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E (2017) Dysbiosis and the immune system. Nat Rev Immunol 17(4):219–232

    Article  CAS  PubMed  Google Scholar 

  • Liang S, Wang T, Hu X, Luo J, Li W, Wu X, Duan Y, Jin F (2015) Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress. Neuroscience 310:561–577

    Article  CAS  PubMed  Google Scholar 

  • Long-Smith C, O’Riordan KJ, Clarke G, Stanton C, Dinan TG, Cryan JF (2020) Microbiota-gut-brain axis: new therapeutic opportunities. Annu Rev Pharmacol Toxicol 60:477–502

    Article  CAS  PubMed  Google Scholar 

  • Lopetuso LR, Napoli M, Rizzatti G, Scaldaferri F, Franceschi F, Gasbarrini A (2018) Considering gut microbiota disturbance in the management of Helicobacter pylori infection. Exp Rev Gastroenterol Hepatol 12(9):899–906

    Article  CAS  Google Scholar 

  • Lorente-Picón M, Laguna A (2021) New avenues for Parkinson’s disease therapeutics: disease-modifying strategies based on the gut microbiota. Biomolecules 11(3):433. https://doi.org/10.3390/biom11030433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lubomski M, Tan AH, Lim SY, Holmes AJ, Davis RL, Sue CM (2020) Parkinson’s disease and the gastrointestinal microbiome. J Neurol 267(9):2507–2523

    Article  PubMed  Google Scholar 

  • Maes M, Kubera M, Leunis JC (2008) The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett 29(1):117–124

    PubMed  Google Scholar 

  • Magistrelli L, Amoruso A, Mogna L, Graziano T, Cantello R, Pane M, Comi C (2019) Probiotics may have beneficial effects in parkinson’s disease: in vitro evidence. Front Immunol 10:969–969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGee DJ, Lu XH, Disbrow EA (2018) Stomaching the possibility of a pathogenic role for helicobacter pylori in parkinson’s Disease. J Parkinsons Dis 8(3):367–374

    Article  PubMed  PubMed Central  Google Scholar 

  • Miraglia F, Colla E (2019) Microbiome, Parkinson's disease and molecular mimicry. Cells 8(3)

  • Mulak A, Bonaz B (2015) Brain-gut-microbiota axis in Parkinson’s disease. World J Gastroenterol 21(37):10609–10620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Myers K (2019) Gut/brain axis and its role in Parkinson’s disease progression. unpublished thesis (Creative Components), Iowa State University

  • Nag N, Jelinek GA (2019) A narrative review of lifestyle factors associated with Parkinson’s disease risk and progression. Neurodegener Dis 19(2):51–59

    Article  PubMed  Google Scholar 

  • O’Donovan SM, Crowley EK, Brown JR, O’Sullivan O, O’Leary OF, Timmons S, Nolan YM, Clarke DJ, Hyland NP, Joyce SA, Sullivan AM, O’Neill C (2020) Nigral overexpression of α-synuclein in a rat Parkinson’s disease model indicates alterations in the enteric nervous system and the gut microbiome. Neurogastroenterol Motil 32(1):e13726

    CAS  PubMed  Google Scholar 

  • Ojetti V, Bruno G, Ainora ME, Gigante G, Rizzo G, Roccarina D, Gasbarrini A (2012) Impact of Lactobacillus reuteri supplementation on anti-helicobacter pylori levofloxacin-based second-line therapy. Gastroenterol Res Pract 740381

  • Oligschlaeger Y, Yadati T, Houben T, Oliván CMC, Shiri-Sverdlov R (2019) Inflammatory bowel disease: a stressed, “gut/feeling.” Cells 8(7):659. https://doi.org/10.3390/cells8070659

    Article  CAS  PubMed Central  Google Scholar 

  • Pandey KR, Naik SR, Vakil BV (2015) Probiotics, prebiotics and synbiotics—a review. J Food Sci Technol 52(12):7577–7587. https://doi.org/10.1007/s13197-015-1921-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parashar A, Udayabanu M (2017) Gut microbiota: implications in Parkinson’s disease. Parkinsonism Relat Disord 38:1–7

    Article  PubMed  PubMed Central  Google Scholar 

  • Peelaerts W, Baekelandt V (2016) ɑ-Synuclein strains and the variable pathologies of synucleinopathies. J Neurochem 139(Suppl 1):256–274

    Article  CAS  PubMed  Google Scholar 

  • Perez-Pardo P, Kliest T, Dodiya HB, Broersen LM, Garssen J, Keshavarzian A, Kraneveld AD (2017) The gut-brain axis in Parkinson’s disease: possibilities for food-based therapies. Eur J Pharmacol 817:86–95

    Article  CAS  PubMed  Google Scholar 

  • Petrov VA, Saltykova IV, Zhukova IA, Alifirova VM, Zhukova NG, Dorofeeva YB, Tyakht AV, Kovarsky BA, Alekseev DG, Kostryukova ES, Mironova YS, Izhboldina OP, Nikitina MA, Perevozchikova TV, Fait EA, Babenko VV, Vakhitova MT, Govorun VM, Sazonov AE (2017) Analysis of gut microbiota in patients with Parkinson’s disease. Bull Exp Biol Med 162(6):734–737

    Article  CAS  PubMed  Google Scholar 

  • Pierantozzi M, Pietroiusti A, Sancesario G, Lunardi G, Fedele E, Giacomini P, Frasca S, Galante A, Marciani MG, Stanzione P (2001) Reduced L-dopa absorption and increased clinical fluctuations in Helicobacter pylori-infected Parkinson’s disease patients. Neurol Sci 22(1):89–91

    Article  CAS  PubMed  Google Scholar 

  • Pietrucci D, Cerroni R, Unida V, Farcomeni A, Pierantozzi M, Mercuri NB, Biocca S, Stefani A, Desideri A (2019) Dysbiosis of gut microbiota in a selected population of Parkinson’s patients. Parkinsonism Relat Disord 65:124–130

    Article  PubMed  Google Scholar 

  • Pietrucci D, Teofani A, Unida V, Cerroni R, Biocca S, Stefani A, Desideri A (2020) Can gut microbiota be a good predictor for Parkinson’s disease? A machine learning approach. Brain Sci 10(4):242

    Article  CAS  PubMed Central  Google Scholar 

  • Pinter B, Diem-Zangerl A, Wenning GK, Scherfler C, Oberaigner W, Seppi K, Poewe W (2015) Mortality in Parkinson’s disease: a 38-year follow-up study. Mov Disord 30(2):266–269

    Article  PubMed  Google Scholar 

  • Rahne KE, Tagesson C, Nyholm D (2013) Motor fluctuations and Helicobacter pylori in Parkinson’s disease. J Neurol 260(12):2974–2980

    Article  PubMed  Google Scholar 

  • Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167(6):1469-1480.e12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheperjans F (2016) Gut microbiota, 1013 new pieces in the Parkinson’s disease puzzle. Curr Opin Neurol 29(6):773–780

    Article  CAS  PubMed  Google Scholar 

  • Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P (2015) Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 30(3):350–358

    Article  PubMed  Google Scholar 

  • Schulz C, Schütte K, Koch N, Vilchez-Vargas R, Wos-Oxley ML, Oxley APA, Vital M, Malfertheiner P, Pieper DH (2018) The active bacterial assemblages of the upper GI tract in individuals with and without <em>Helicobacter</em> infection. Gut 67(2):216

    Article  CAS  PubMed  Google Scholar 

  • Sender R, Fuchs S, Milo R (2016) Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164(3):337–340

    Article  CAS  PubMed  Google Scholar 

  • Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH (2012) Is alpha-synuclein in the colon a biomarker for premotor Parkinson’s disease? Evidence from 3 cases. Mov Disord 27(6):716–719

    Article  PubMed  Google Scholar 

  • Silva YP, Bernardi A, Frozza RL (2020) The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol 11(25)

  • Slikker W, Paule, Merle G,Wang C (2018) Handbook of developmental neurotoxicology, Second Edition ed. Academic Press.

  • Smith K, McCoy KD, Macpherson AJ (2007) Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 19(2):59–69

    Article  CAS  PubMed  Google Scholar 

  • Stephens MAC, Mccaul ME, Wand GS (2014) The potential role of glucocorticoids and the HPA axis in alcohol dependence. Neurobiol Alcohol Dependence. https://doi.org/10.1016/b978-0-12-405941-2.00021-3

    Article  Google Scholar 

  • Stoilova T, Colombo L, Forloni G, Tagliavini F, Salmona M (2013) A new face for old antibiotics: tetracyclines in treatment of amyloidoses. J Med Chem 56(15):5987–6006. https://doi.org/10.1021/jm400161p

    Article  CAS  PubMed  Google Scholar 

  • Steiner JA, Quansah E, Brundin P (2018) The concept of alpha-synuclein as a prion-like protein: ten years after. Cell Tissue Res 373(1):161–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stokholm MG, Danielsen EH, Hamilton-Dutoit SJ, Borghammer P (2016) Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann Neurol 79(6):940–949

    Article  CAS  PubMed  Google Scholar 

  • Sun MF, Zhu YL, Zhou ZL, Jia XB, Xu YD, Yang Q, Cui C, Shen YQ (2018) Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson’s disease mice: gut microbiota, glial reaction and TLR4/TNF-α signaling pathway. Brain Behav Immun 70:48–60

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Zhang M, Chen C-C, Gillilland M, Sun X, El-Zaatari M, Huffnagle GB, Young VB, Zhang J, Hong S-C, Chang Y-M, Gumucio DL, Owyang C, Kao JY (2013) Stress-induced corticotropin-releasing hormone-mediated NLRP6 inflammasome inhibition and transmissible enteritis in mice. Gastroenterology 144(7):1478–87, 1487.e1–8

  • Svensson E, Horváth-Puhó E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P, Sørensen HT (2015) Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol 78(4):522–529

    Article  PubMed  Google Scholar 

  • Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R, Kouchaki E, Bahmani F, Borzabadi S, Oryan S, Mafi A, Asemi Z (2019) Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial. Clin Nutr 38(3):1031–1035

    Article  CAS  PubMed  Google Scholar 

  • Ternák G, Kuti D, Kovács KJ (2020) Dysbiosis in Parkinson’s disease might be triggered by certain antibiotics. Med Hypotheses 137:109564

    Article  PubMed  CAS  Google Scholar 

  • Tysnes OB, Storstein A (2017) Epidemiology of Parkinson’s disease. J Neural Transm (vienna) 124(8):901–905

    Article  Google Scholar 

  • Ugalde CL, Lawson VA, Finkelstein DI, Hill AF (2019) The role of lipids in α-synuclein misfolding and neurotoxicity. J Biol Chem 294(23):9016–9028

    Article  PubMed  PubMed Central  Google Scholar 

  • Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, Faßbender K, Schwiertz A, Schäfer KH (2016) Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord 32:66–72

    Article  PubMed  Google Scholar 

  • Yang D, Zhao D, Ali Shah SZ, Wu W, Lai M, Zhang X, Li J, Guan Z, Zhao H, Li W, Gao H, Zhou X, Yang L (2019) The role of the gut microbiota in the Pathogenesis of Parkinson’s disease. Front Neurol 10:1155–1155

    Article  PubMed  PubMed Central  Google Scholar 

  • Zheng D, Liwinski T, Elinav E (2020) Interaction between microbiota and immunity in health and disease. Cell Res 30(6):492–506

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Sara Ayman Moustafa, Shrouk Mohamed, Abdelhameed Dawood and Jihan Azar have contributed equally to this work.

Authors and Affiliations

  1. Institute of Global Health and Human Ecology (IGHHE) Graduate Program, The American University in Cairo, New Cairo, 11835, Egypt

    Sara Ayman Moustafa, Jihan Azar & Mohamed Salama

  2. Nanotechnology Graduate Program, The American University in Cairo, New Cairo, 11835, Egypt

    Shrouk Mohamed

  3. Biotechnology Graduate Program, The American University in Cairo, New Cairo, 11835, Egypt

    Abdelhameed Dawood

  4. Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Ekramy Elmorsy & Mohamed Salama

  5. Pathology Department, Faculty of Medicine, Northern Border University-ARAR, North Region, Arar, Saudi Arabia

    Ekramy Elmorsy

  6. Molecular, Genetic and Population Health Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK

    Noura A. M. Rizk

  7. Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland

    Mohamed Salama

Authors
  1. Sara Ayman Moustafa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shrouk Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdelhameed Dawood
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jihan Azar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ekramy Elmorsy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Noura A. M. Rizk
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohamed Salama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohamed Salama.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moustafa, S.A., Mohamed, S., Dawood, A. et al. Gut brain axis: an insight into microbiota role in Parkinson’s disease. Metab Brain Dis 36, 1545–1557 (2021). https://doi.org/10.1007/s11011-021-00808-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-021-00808-2

Keywords

Search

Navigation