nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2023-1-90-96nnp-1961Research ArticleREVIEWSОБЗОРЫThe gut microbiome as a factor in the development of Parkinson's diseaseСостояние микробиома кишечника как фактор развития болезни Паркинсонаhttps://orcid.org/0000-0002-2645-5842БрсикянЛ. А.BrsikyanL. A.

Лусине Арамайисовна Брсикян

119991, Москва, Большая Пироговская, 2, стр. 4

Lusine Aramayisovna Brsikyan

119991, Moscow, Bolshaya Pirogovskaya St., 2-4

lusine-7@mail.ruhttps://orcid.org/0000-0003-1312-120XПолуэктоваЕ. А.PoluektovaE. A.

119991, Москва, Большая Пироговская, 2, стр. 4

119991, Moscow, Bolshaya Pirogovskaya St., 2-4

https://orcid.org/0000-0001-6215-0918ПолуэктовМ. Г.PoluektovM. G.

119991, Москва, Большая Пироговская, 2, стр. 4

119991, Moscow, Bolshaya Pirogovskaya St., 2-4

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)Russian Federation2023190220231519096Copyright © Brsikyan L.A., Poluektova E.A., Poluektov M.G., 20232023Брсикян Л.А., Полуэктова Е.А., Полуэктов М.Г.Brsikyan L.A., Poluektova E.A., Poluektov M.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/1961

Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive death of dopaminergic neurons in the substantia nigra of the brain and the deposition of α-synuclein in the form of Lewy bodies in other parts of the brain. Characteristic manifestations of this disease, along with motor symptoms, are the gastrointestinal tract disorders, accompanied by a change in the cellular composition of the intestinal biocenosis. This made it possible to propose the so-called "intestinal" theory of the PD origin. According to this theory, degenerative changes begin in the nervous apparatus of the large intestine, and then spread to the brain. Changes in the intestinal microbiota composition can contribute to the development of the neurodegenerative process through neural, immune, endocrine mechanisms, as well as through biologically active substances.

Болезнь Паркинсона (БП) – нейродегенеративное заболевание, характеризующееся прогрессирующей гибелью дофаминсодержащих нейронов черной субстанции головного мозга и отложением α-синуклеина в других его отделах в виде телец Леви. Характерными проявлениями этого заболевания, наряду с моторными симптомами, являются расстройства деятельности желудочно-кишечного тракта, сопровождающиеся изменением клеточного состава биоценоза кишечника. Это дало возможность предложить так называемую «кишечную» теорию происхождения БП. Согласно ей дегенеративные изменения начинаются в нервном аппарате толстого кишечника, а затем распространяются в головной мозг. Изменение состава кишечной микробиоты может способствовать развитию нейродегенеративного процесса через невральный, иммунный, эндокринный механизмы, а также посредством биологически активных веществ.

болезнь Паркинсонаα-синуклеин»ось «кишечник–мозг»кишечная микробиотаблуждающий нерввоспалениеактивация микроглииэнтероэндокринные клеткикороткоцепочечные жирные кислотыParkinson's diseaseα-synucleingut–brain axisintestinal microbiotanervus vagusinflammationactivation of microgliaenteroendocrine cellsshort chain fatty acidsReferencesNair AT, Ramachandran V, Joghee NM, et al. Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review. J Neurogastroenterol Motil. 2018 Jan 30;24(1):30-42. doi:10.5056/jnm17105Nair AT, Ramachandran V, Joghee NM, et al. Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review. J Neurogastroenterol Motil. 2018 Jan 30;24(1):30-42. doi:10.5056/jnm17105Sulzer D. Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease. Trends Neurosci. 2007 May;30(5):244-50. doi:10.1016/j.tins.2007.03.009. Epub 2007 Apr 5.Sulzer D. Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease. Trends Neurosci. 2007 May;30(5):244-50. doi:10.1016/j.tins.2007.03.009. Epub 2007 Apr 5.O’Callaghan C, Lewis SJG. Cognition in Parkinson's Disease. Int Rev Neurobiol. 2017;133:557-83. doi:10.1016/bs.irn.2017.05.002. Epub 2017 Jun 16.O’Callaghan C, Lewis SJG. Cognition in Parkinson's Disease. Int Rev Neurobiol. 2017;133:557-83. doi:10.1016/bs.irn.2017.05.002. Epub 2017 Jun 16.Pont-Sunyer C, Hotter A, Gaig C, et al. The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Mov Disord. 2015 Feb;30(2):229-37. doi:10.1002/mds.26077. Epub 2014 Dec 1.Pont-Sunyer C, Hotter A, Gaig C, et al. The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Mov Disord. 2015 Feb;30(2):229-37. doi:10.1002/mds.26077. Epub 2014 Dec 1.Braak H, Rüb U, Gai WP, Del Tredici K. Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna). 2003 May;110(5):517-36. doi:10.1007/s00702-002-0808-2Braak H, Rüb U, Gai WP, Del Tredici K. Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna). 2003 May;110(5):517-36. doi:10.1007/s00702-002-0808-2Гапонов ДО, Пригодина ЕВ, Грудина ТВ, Доросевич АЕ. Современный взгляд на патогенетические механизмы прогрессирования болезни Паркинсона. Русский медицинский журнал. 2018;12(1):66-72.Gaponov DO, Prigodina EV, Grudina TV, Dorosevich AE. Modern view on the pathogenetic mechanisms of Parkinson’s disease progression. RMJ. 2018;12(1):66-72 (In Russ.).Hansen C, Angot E, Bergstrom AL, et al. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest. 2011 Feb;121(2):715-25. doi:10.1172/JCI43366. Epub 2011 Jan 18.Hansen C, Angot E, Bergstrom AL, et al. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest. 2011 Feb;121(2):715-25. doi:10.1172/JCI43366. Epub 2011 Jan 18.Brundin P, Li JY, Holton JL, et al. Research in motion: the enigma of Parkinson’s disease pathology spread. Nat Rev Neurosci. 2008 Oct;9(10):741-5. doi:10.1038/nrn2477. Epub 2008 Sep 4.Brundin P, Li JY, Holton JL, et al. Research in motion: the enigma of Parkinson’s disease pathology spread. Nat Rev Neurosci. 2008 Oct;9(10):741-5. doi:10.1038/nrn2477. Epub 2008 Sep 4.Goedert M, Falcon B, Clavaguera F, Tolnay M. Prion-like mechanisms in the pathogenesis of taupathies and synucleinopathies. Curr Neurol Neurosci Rep. 2014 Nov;14(11):495. doi:10.1007/s11910-014-0495-zGoedert M, Falcon B, Clavaguera F, Tolnay M. Prion-like mechanisms in the pathogenesis of taupathies and synucleinopathies. Curr Neurol Neurosci Rep. 2014 Nov;14(11):495. doi:10.1007/s11910-014-0495-zBraak H, de Vos RA, Bohl J, Del Tredici K. Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett. 2006 Mar 20;396(1):67-72. doi:10.1016/j.neulet.2005.11.012. Epub 2005 Dec 5.Braak H, de Vos RA, Bohl J, Del Tredici K. Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett. 2006 Mar 20;396(1):67-72. doi:10.1016/j.neulet.2005.11.012. Epub 2005 Dec 5.Kim S, Kwon SH, Kam TI, et al. Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019 Aug 21;103(4):627-41.e7. doi:10.1016/j.neuron.2019.05.035. Epub 2019 Jun 26.Kim S, Kwon SH, Kam TI, et al. Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019 Aug 21;103(4):627-41.e7. doi:10.1016/j.neuron.2019.05.035. Epub 2019 Jun 26.Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol. 2014 Oct 21;20(39):14105-25. doi:10.3748/wjg.v20.i39.14105Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol. 2014 Oct 21;20(39):14105-25. doi:10.3748/wjg.v20.i39.14105Gracie DJ, Guthrie EA, Hamlin PJ, Ford AC. Bi-directionality of Brain–Gut Interactions in Patients With Inflammatory Bowel Disease. Gastroenterology. 2018 May;154(6):1635-46.e3. doi:10.1053/j.gastro.2018.01.027. Epub 2018 Jan 31.Gracie DJ, Guthrie EA, Hamlin PJ, Ford AC. Bi-directionality of Brain–Gut Interactions in Patients With Inflammatory Bowel Disease. Gastroenterology. 2018 May;154(6):1635-46.e3. doi:10.1053/j.gastro.2018.01.027. Epub 2018 Jan 31.Mulak A, Bonaz B. Brain-gut-microbiota axis in Parkinson's disease. World J Gastroenterol. 2015 Oct 7;21(37):10609-20. doi:10.3748/wjg.v21.i37.10609Mulak A, Bonaz B. Brain-gut-microbiota axis in Parkinson's disease. World J Gastroenterol. 2015 Oct 7;21(37):10609-20. doi:10.3748/wjg.v21.i37.10609Shannon KM, Keshavarzian A, Dodiya HB, et al. Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord. 2012 May;27(6):716-9. doi:10.1002/mds.25020. Epub 2012 May 1.Shannon KM, Keshavarzian A, Dodiya HB, et al. Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord. 2012 May;27(6):716-9. doi:10.1002/mds.25020. Epub 2012 May 1.Shannon KM, Keshavarzian A, Mutlu E, et al. Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease. Mov Disord. 2012 May;27(6):709-15. doi:10.1002/mds.23838. Epub 2011 Jul 15.Shannon KM, Keshavarzian A, Mutlu E, et al. Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease. Mov Disord. 2012 May;27(6):709-15. doi:10.1002/mds.23838. Epub 2011 Jul 15.Ulusoy A, Phillips RJ, Helwig M, et al. Brain-to-stomach transfer of α-synuclein via vagal preganglionic projections. Acta Neuropathol. 2017 Mar;133(3):381-93. doi:10.1007/s00401-016-1661-y. Epub 2016 Dec 23.Ulusoy A, Phillips RJ, Helwig M, et al. Brain-to-stomach transfer of α-synuclein via vagal preganglionic projections. Acta Neuropathol. 2017 Mar;133(3):381-93. doi:10.1007/s00401-016-1661-y. Epub 2016 Dec 23.Breen DP, Halliday GM, Lang AE. Gut–brain axis and the spread of α-synuclein pathology: vagal highway or dead end? Mov Disord. 2019 Mar;34(3):307-16. doi:10.1002/mds.27556. Epub 2019 Jan 17.Breen DP, Halliday GM, Lang AE. Gut–brain axis and the spread of α-synuclein pathology: vagal highway or dead end? Mov Disord. 2019 Mar;34(3):307-16. doi:10.1002/mds.27556. Epub 2019 Jan 17.Svensson E, Horvath-Puho E, Thomsen RW, et al. Vagotomy and subsequent risk of Parkinson's disease. Ann Neurol. 2015 Oct;78(4):522-9. doi:10.1002/ana.24448. Epub 2015 Jul 17.Svensson E, Horvath-Puho E, Thomsen RW, et al. Vagotomy and subsequent risk of Parkinson's disease. Ann Neurol. 2015 Oct;78(4):522-9. doi:10.1002/ana.24448. Epub 2015 Jul 17.Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: a Swedish register-based matched-cohort study. Neurology. 2017 May 23;88(21):1996-2002. doi:10.1212/WNL.0000000000003961. Epub 2017 Apr 26.Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: a Swedish register-based matched-cohort study. Neurology. 2017 May 23;88(21):1996-2002. doi:10.1212/WNL.0000000000003961. Epub 2017 Apr 26.Tynes OB, Kenborg L, Herlofson K, et al. Does vagotomy reduce the risk of Parkinson’s disease? Ann Neurol. 2015 Dec;78(6):1011-2. doi:10.1002/ana.24531. Epub 2015 Nov 14.Tynes OB, Kenborg L, Herlofson K, et al. Does vagotomy reduce the risk of Parkinson’s disease? Ann Neurol. 2015 Dec;78(6):1011-2. doi:10.1002/ana.24531. Epub 2015 Nov 14.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(12):e28032. doi:10.1371/journal.pone.0028032. Epub 2011 Dec 1.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(12):e28032. doi:10.1371/journal.pone.0028032. Epub 2011 Dec 1.Kelly LP, Carvey PM, Keshavarzian A, et al. Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease. Mov Disord. 2014 Jul;29(8):999-1009. doi:10.1002/mds.25736. Epub 2013 Nov 4.Kelly LP, Carvey PM, Keshavarzian A, et al. Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease. Mov Disord. 2014 Jul;29(8):999-1009. doi:10.1002/mds.25736. Epub 2013 Nov 4.Kim WG, Mohney RP, Wilson B, et al. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci. 2000 Aug 15;20(16):6309-16. doi:10.1523/JNEUROSCI.20-16-06309.2000Kim WG, Mohney RP, Wilson B, et al. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci. 2000 Aug 15;20(16):6309-16. doi:10.1523/JNEUROSCI.20-16-06309.2000Sampson TR, Debelius JW, Thron T, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016 Dec 1;167(6):1469-80.e12. doi:10.1016/j.cell.2016.11.018Sampson TR, Debelius JW, Thron T, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016 Dec 1;167(6):1469-80.e12. doi:10.1016/j.cell.2016.11.018DiBaise JK, Crowell MD, Driver-Dunckley E, et al. Weight Loss in Parkinson's Disease: No Evidence for Role of Small Intestinal Bacterial Overgrowth. J Parkinsons Dis. 2018;8(4):571-81. doi:10.3233/JPD-181386DiBaise JK, Crowell MD, Driver-Dunckley E, et al. Weight Loss in Parkinson's Disease: No Evidence for Role of Small Intestinal Bacterial Overgrowth. J Parkinsons Dis. 2018;8(4):571-81. doi:10.3233/JPD-181386Fasano A, Bove F, Gabrielli M, et al. The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord. 2013 Aug;28(9):1241-9. doi:10.1002/mds.25522. Epub 2013 May 27.Fasano A, Bove F, Gabrielli M, et al. The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord. 2013 Aug;28(9):1241-9. doi:10.1002/mds.25522. Epub 2013 May 27.Tan AH, Mahadeva S, Thalha AM, et al. Small intestinal bacterial overgrowth in Parkinson’s disease. Parkinsonism Relat Disord. 2014 May;20(5):535-40. doi:10.1016/j.parkreldis.2014.02.019. Epub 2014 Mar 2.Tan AH, Mahadeva S, Thalha AM, et al. Small intestinal bacterial overgrowth in Parkinson’s disease. Parkinsonism Relat Disord. 2014 May;20(5):535-40. doi:10.1016/j.parkreldis.2014.02.019. Epub 2014 Mar 2.Gabrielli M, Bonazzi P, Scarpellini E, et al. Prevalence of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord. 2011 Apr;26(5):889-92. doi:10.1002/mds.23566. Epub 2011 Feb 1.Gabrielli M, Bonazzi P, Scarpellini E, et al. Prevalence of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord. 2011 Apr;26(5):889-92. doi:10.1002/mds.23566. Epub 2011 Feb 1.Dobbs RJ, Charlett A, Dobbs SM, et al. Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth: A surveillance study. Gut Pathogens. 2012 Oct 19;4(1):12. doi:10.1186/1757-4749-4-12Dobbs RJ, Charlett A, Dobbs SM, et al. Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth: A surveillance study. Gut Pathogens. 2012 Oct 19;4(1):12. doi:10.1186/1757-4749-4-12Niu XL, Liu L, Song ZX, et al. Prevalence of small intestinal bacterial overgrowth in Chinese patients with Parkinson’s disease. J Neural Transm (Vienna). 2016 Dec;123(12):1381-6. doi:10.1007/s00702-016-1612-8. Epub 2016 Sep 2.Niu XL, Liu L, Song ZX, et al. Prevalence of small intestinal bacterial overgrowth in Chinese patients with Parkinson’s disease. J Neural Transm (Vienna). 2016 Dec;123(12):1381-6. doi:10.1007/s00702-016-1612-8. Epub 2016 Sep 2.Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014 Nov 19;6(263):263ra158. doi:10.1126/scitranslmed.3009759Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014 Nov 19;6(263):263ra158. doi:10.1126/scitranslmed.3009759Sui YT, Bullock KM, Erickson MA, et al. Alpha synuclein is transported into and out of the brain by the blood-brain barrier. Peptides. 2014 Dec;62:197-202. doi:10.1016/j.peptides.2014.09.018. Epub 2014 Sep 30.Sui YT, Bullock KM, Erickson MA, et al. Alpha synuclein is transported into and out of the brain by the blood-brain barrier. Peptides. 2014 Dec;62:197-202. doi:10.1016/j.peptides.2014.09.018. Epub 2014 Sep 30.Villaran RF, Espinosa-Oliva AM, Sarmiento M, et al. Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease. J Neurochem. 2010 Sep;114(6):1687-700. doi:10.1111/j.1471-4159.2010.06879.x. Epub 2010 Aug 19.Villaran RF, Espinosa-Oliva AM, Sarmiento M, et al. Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease. J Neurochem. 2010 Sep;114(6):1687-700. doi:10.1111/j.1471-4159.2010.06879.x. Epub 2010 Aug 19.Dobbs RJ, Dobbs SM, Weller C, et al. Helicobacter hypothesis for idiopathic parkinsonism: before and beyond. Helicobacter. 2008 Oct;13(5):309-22. doi:10.1111/j.1523-5378.2008.00622.xDobbs RJ, Dobbs SM, Weller C, et al. Helicobacter hypothesis for idiopathic parkinsonism: before and beyond. Helicobacter. 2008 Oct;13(5):309-22. doi:10.1111/j.1523-5378.2008.00622.xCharlett A, Dobbs RJ, Dobbs SM, et al. Blood profile holds clues to role of infection in a premonitory state for idiopathic parkinsonism and of gastrointestinal infection in established disease. Gut Pathogens. 2009 Nov 26;1(1):20. doi:10.1186/1757-4749-1-20Charlett A, Dobbs RJ, Dobbs SM, et al. Blood profile holds clues to role of infection in a premonitory state for idiopathic parkinsonism and of gastrointestinal infection in established disease. Gut Pathogens. 2009 Nov 26;1(1):20. doi:10.1186/1757-4749-1-20Bodea LG, Wang Y, Linnartz-Gerlach B, et al. Neurodegeneration by activation of the microglial complement-phagosome pathway. J Neurosci. 2014 Jun 18;34(25):8546-56. doi:10.1523/JNEUROSCI.5002-13.2014Bodea LG, Wang Y, Linnartz-Gerlach B, et al. Neurodegeneration by activation of the microglial complement-phagosome pathway. J Neurosci. 2014 Jun 18;34(25):8546-56. doi:10.1523/JNEUROSCI.5002-13.2014Alvarez-Arellano L, Maldonado-Bernal C. Helicobacter pylori and neurological diseases: Married by the laws of inflammation. World J Gastrointest Pathophysiol. 2014 Nov 15;5(4):400-4. doi:10.4291/wjgp.v5.i4.400Alvarez-Arellano L, Maldonado-Bernal C. Helicobacter pylori and neurological diseases: Married by the laws of inflammation. World J Gastrointest Pathophysiol. 2014 Nov 15;5(4):400-4. doi:10.4291/wjgp.v5.i4.400Block ML, Zecca L, Hong JS. Microgliamediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007 Jan;8(1):57-69. doi:10.1038/nrn2038Block ML, Zecca L, Hong JS. Microgliamediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007 Jan;8(1):57-69. doi:10.1038/nrn2038Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990;39(1):151-70. doi:10.1016/0306-4522(90)90229-wLawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990;39(1):151-70. doi:10.1016/0306-4522(90)90229-wPott Godoy MC, Tarelli R, Ferrari CC, et al. Central and systemic IL-1 exacerbatesneurodegeneration and motor symptoms in a model of Parkinson’s disease. Brain. 2008 Jul;131(Pt 7):1880-94. doi:10.1093/brain/awn101. Epub 2008 May 26.Pott Godoy MC, Tarelli R, Ferrari CC, et al. Central and systemic IL-1 exacerbatesneurodegeneration and motor symptoms in a model of Parkinson’s disease. Brain. 2008 Jul;131(Pt 7):1880-94. doi:10.1093/brain/awn101. Epub 2008 May 26.Perry VH, Teeling J. Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Semin Immunopathol. 2013 Sep;35(5):601-12. doi:10.1007/s00281-013-0382-8. Epub 2013 Jun 4.Perry VH, Teeling J. Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Semin Immunopathol. 2013 Sep;35(5):601-12. doi:10.1007/s00281-013-0382-8. Epub 2013 Jun 4.Devos D, Lebouvier T, Lardeux B, et al. Colonic inflammation in Parkinson’s disease. Neurobiol Dis. 2013 Feb;50:42-8. doi:10.1016/j.nbd.2012.09.007. Epub 2012 Sep 24.Devos D, Lebouvier T, Lardeux B, et al. Colonic inflammation in Parkinson’s disease. Neurobiol Dis. 2013 Feb;50:42-8. doi:10.1016/j.nbd.2012.09.007. Epub 2012 Sep 24.Trudler D, Farfara D, Frenkel D. Toll-like receptors expression and signaling in glia cells in neuro-amyloidogenic diseases: towards future therapeutic application. Mediators Inflamm. 2010;2010:497987. doi:10.1155/2010/497987. Epub 2010 Jul 25.Trudler D, Farfara D, Frenkel D. Toll-like receptors expression and signaling in glia cells in neuro-amyloidogenic diseases: towards future therapeutic application. Mediators Inflamm. 2010;2010:497987. doi:10.1155/2010/497987. Epub 2010 Jul 25.Beeraud D, Maguire-Zeiss KA. Misfolded α-synuclein and Toll-like receptors: therapeutic targets for Parkinson’s disease. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1(0 1):S17-20. doi:10.1016/S1353-8020(11)70008-6Beeraud D, Maguire-Zeiss KA. Misfolded α-synuclein and Toll-like receptors: therapeutic targets for Parkinson’s disease. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1(0 1):S17-20. doi:10.1016/S1353-8020(11)70008-6Friedland RP. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration. J Alzheimers Dis. 2015;45(2):349-62. doi:10.3233/JAD-142841Friedland RP. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration. J Alzheimers Dis. 2015;45(2):349-62. doi:10.3233/JAD-142841Appelmelk BJ, Negrini R, Moran AP, Kuipers EJ. Molecular mimicry between Helicobacter pylori and the host. Trends Microbiol. 1997 Feb;5(2):70-3. doi:10.1016/S0966-842X(96)10084-6Appelmelk BJ, Negrini R, Moran AP, Kuipers EJ. Molecular mimicry between Helicobacter pylori and the host. Trends Microbiol. 1997 Feb;5(2):70-3. doi:10.1016/S0966-842X(96)10084-6Bohorquez DV, Shahid RA, Erdmann A, et al. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest. 2015 Feb;125(2):782-6. doi:10.1172/JCI78361. Epub 2015 Jan 2.Bohorquez DV, Shahid RA, Erdmann A, et al. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest. 2015 Feb;125(2):782-6. doi:10.1172/JCI78361. Epub 2015 Jan 2.Liddle RA. Parkinson's disease from the gut. Brain Res. 2018 Aug 15;1693(Pt B):201-6. doi:10.1016/j.brainres.2018.01.010. Epub 2018 Jan 31.Liddle RA. Parkinson's disease from the gut. Brain Res. 2018 Aug 15;1693(Pt B):201-6. doi:10.1016/j.brainres.2018.01.010. Epub 2018 Jan 31.Chandra R, Hiniker A, Kuo YM, et al. α-Synuclein in gut endocrine cells and its implications for Parkinson's disease. JCI Insight. 2017 Jun 15;2(12):e92295. doi:10.1172/jci.insight.92295Chandra R, Hiniker A, Kuo YM, et al. α-Synuclein in gut endocrine cells and its implications for Parkinson's disease. JCI Insight. 2017 Jun 15;2(12):e92295. doi:10.1172/jci.insight.92295Caputi V, Giron MC. Microbiome-GutBrain Axis and Toll-Like Receptors in Parkinson's Disease. Int J Mol Sci. 2018;19(6):1689.Caputi V, Giron MC. Microbiome-GutBrain Axis and Toll-Like Receptors in Parkinson's Disease. Int J Mol Sci. 2018;19(6):1689.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 Nov;32:66-72. doi:10.1016/j.parkreldis.2016.08.019. Epub 2016 Aug 26.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 Nov;32:66-72. doi:10.1016/j.parkreldis.2016.08.019. Epub 2016 Aug 26.Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012 Oct;13(10):701-12. doi:10.1038/nrn3346. Epub 2012 Sep 12.Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012 Oct;13(10):701-12. doi:10.1038/nrn3346. Epub 2012 Sep 12.Ganapathy V, Thangaraju M, Prasad PD, et al. Transporters and receptors for short-chain fatty acids as the molecular link between colonic bacteria and the host. Curr Opin Pharmacol. 2013 Dec;13(6):869-74. doi:10.1016/j.coph.2013.08.006. Epub 2013 Aug 23.Ganapathy V, Thangaraju M, Prasad PD, et al. Transporters and receptors for short-chain fatty acids as the molecular link between colonic bacteria and the host. Curr Opin Pharmacol. 2013 Dec;13(6):869-74. doi:10.1016/j.coph.2013.08.006. Epub 2013 Aug 23.Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014 Jan 16;40(1):128-39. doi:10.1016/j.immuni.2013.12.007. Epub 2014 Jan 9.Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014 Jan 16;40(1):128-39. doi:10.1016/j.immuni.2013.12.007. Epub 2014 Jan 9.Hamer HM, Jonkers D, Venema K, et al. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19. doi:10.1111/j.1365-2036.2007.03562.x. Epub 2007 Oct 25.Hamer HM, Jonkers D, Venema K, et al. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19. doi:10.1111/j.1365-2036.2007.03562.x. Epub 2007 Oct 25.Canani RB, Costanzo MD, Leone L, et al. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011 Mar 28;17(12):1519-28. doi:10.3748/wjg.v17.i12.1519Canani RB, Costanzo MD, Leone L, et al. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011 Mar 28;17(12):1519-28. doi:10.3748/wjg.v17.i12.1519Lal S, Kirkup AJ, Brunsden AM, et al. Vagal afferent responses to fatty acids of different chain length in the rat. Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G907-15. doi:10.1152/ajpgi.2001.281.4.G907Lal S, Kirkup AJ, Brunsden AM, et al. Vagal afferent responses to fatty acids of different chain length in the rat. Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G907-15. doi:10.1152/ajpgi.2001.281.4.G907Alam R, Abdolmaleky HM, Zhou JR. Microbiome, inflammation, epigenetic alterations, and mental diseases. Am J Med Genet B Neuropsychiatr Genet. 2017 Sep;174(6):651-60. doi:10.1002/ajmg.b.32567. Epub 2017 Jul 10.Alam R, Abdolmaleky HM, Zhou JR. Microbiome, inflammation, epigenetic alterations, and mental diseases. Am J Med Genet B Neuropsychiatr Genet. 2017 Sep;174(6):651-60. doi:10.1002/ajmg.b.32567. Epub 2017 Jul 10.Kountouras J, Zavos C, Polyzos SA, et al. Helicobacter pylori infection and Parkinson's disease: apoptosis as an underlying common contributor. Eur J Neurol. 2012 Jun;19(6):e56. doi:10.1111/j.1468-1331.2012.03695.xKountouras J, Zavos C, Polyzos SA, et al. Helicobacter pylori infection and Parkinson's disease: apoptosis as an underlying common contributor. Eur J Neurol. 2012 Jun;19(6):e56. doi:10.1111/j.1468-1331.2012.03695.x

The authors declare that there are no conflicts of interest present.