MICROBIOTA

microbiotakapak

MICROBIOTA AND NEURODEGENERATIVE DISEASES

Turay Mutlu1
Buğra Selluncak2
Ünal Balıkel3

1Ankara Etlik City Hospital, Department of Neurology, Ankara, Türkiye
2Adana City Hospital, Department of Neurology, Adana, Türkiye
3Hatay Defne State Hospital, Department of Neurology, Hatay, Türkiye

Mutlu T, Selluncak B, Balıkel Ü. Microbiota and Neurodegenerative Diseases. Melek İM, Aydoğan S, eds. Microbiota. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.107-123.

ABSTRACT

Neurodegenerative disease (NDD) can be summarized as an umbrella term for disease groups characterized by the gradual deterioration of neuronal structure and function, particularly in the central nervous system (CNS), and accompanied by chronic-progressive clinical worsening. These disease groups, collectively referred to as NDDs, have a diverse spectrum of manifestations, but are mainly based on conditions that affect vital functions such as dementia, movement disorders and motor neuron disease. The microbiota is closely related to the nervous system as well as other systems. Recent studies suggest that systemic factors may play a role in the development of neurodegenerative diseases in addition to known central pathogenetic mechanisms. The microbiota, which is one of these systemic factors, draws a remarkable profile both with its mysterious aspect waiting to be elucidated and with its potential to enable the development of alternative prevention and treatment methods. Hence, a deeper understanding of this subject, which is likely to be defined as a common pathway underlying current physiopathological models, is promising to produce new solutions by expanding our horizons about neurological diseases that are currently seen as incurable.

Keywords: Microbiota; Neurodegenerative diseases; Pathogenesis; Dementia; Parkinson disease

Referanslar

  1. Lamptey RNL, Chaulagain B, Trivedi R, Gothwal A, Layek B, Singh J. A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics. Int J Mol Sci. 2022 Feb 6;23(3):1851. [Crossref]  [PubMed]  [PMC]
  2. Dugger BN, Dickson DW. Pathology of Neurodegenerative Diseases. Cold Spring Harb Perspect Biol. 2017 Jul 5;9(7):a028035. [Crossref]  [PubMed]  [PMC]
  3. Ghezzi L, Cantoni C, Rotondo E, Galimberti D. The Gut Microbiome-Brain Crosstalk in Neurodegenerative Diseases. Biomedicines. 2022 Jun 23;10(7):1486. [Crossref]  [PubMed]  [PMC]
  4. Duong S, Patel T, Chang F. Dementia: What pharmacists need to know. Can Pharm J (Ott). 2017 Feb 7;150(2):118-129. [Crossref]  [PubMed]  [PMC]
  5. Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and Management of Dementia: Review. JAMA. 2019 Oct 22;322(16):1589-1599. [Crossref]  [PubMed]  [PMC]
  6. Wilson DM 3rd, Cookson MR, Van Den Bosch L, Zetterberg H, Holtzman DM, Dewachter I. Hallmarks of neurodegenerative diseases. Cell. 2023 Feb 16;186(4):693-714. [Crossref]  [PubMed]
  7. Chin KS. Pathophysiology of dementia. Aust J Gen Pract. 2023 Aug;52(8):516-521. [Crossref]  [PubMed]
  8. Shin JH. Dementia Epidemiology Fact Sheet 2022. Ann Rehabil Med. 2022 Apr;46(2):53-59. [Crossref]  [PubMed]  [PMC]
  9. GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022 Feb;7(2):e105-e125. [Crossref]  [PubMed]
  10. Gareau MG. Microbiota-gut-brain axis and cognitive function. Adv Exp Med Biol. 2014;817:357-71. [Crossref]  [PubMed]
  11. Arnoriaga-Rodríguez M, Fernández-Real JM. Microbiota impacts on chronic inflammation and metabolic syndrome - related cognitive dysfunction. Rev Endocr Metab Disord. 2019 Dec;20(4):473-480. [Crossref]  [PubMed]
  12. Proctor C, Thiennimitr P, Chattipakorn N, Chattipakorn SC. Diet, gut microbiota and cognition. Metab Brain Dis. 2017 Feb;32(1):1-17. [Crossref]  [PubMed]
  13. Livingston G, Huntley J, Liu KY, Costafreda SG, Selbæk G, Alladi S, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024 Aug 10;404(10452):572-628. [Crossref]  [PubMed]
  14. Błaszczyk JW. Pathogenesis of Dementia. Int J Mol Sci. 2022 Dec 29;24(1):543. [Crossref]  [PubMed]  [PMC]
  15. Ji D, Chen WZ, Zhang L, Zhang ZH, Chen LJ. Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study. J Neuroinflammation. 2024 Jan 4;21(1):2. [Crossref]  [PubMed]  [PMC]
  16. Fu J, Qin Y, Xiao L, Dai X. Causal relationship between gut microflora and dementia: a Mendelian randomization study. Front Microbiol. 2024 Jan 15;14:1306048. [Crossref]  [PubMed]  [PMC]
  17. Santiago JA, Potashkin JA. The Impact of Disease Comorbidities in Alzheimer's Disease. Front Aging Neurosci. 2021 Feb 12;13:631770. [Crossref]  [PubMed]  [PMC]
  18. Zvěřová M. Clinical aspects of Alzheimer's disease. Clin Biochem. 2019 Oct;72:3-6. [Crossref]  [PubMed]
  19. Fan L, Mao C, Hu X, Zhang S, Yang Z, Hu Z, et al. New Insights Into the Pathogenesis of Alzheimer's Disease. Front Neurol. 2020 Jan 10;10:1312. [Crossref]  [PubMed]  [PMC]
  20. García-Morales V, González-Acedo A, Melguizo-Rodríguez L, Pardo-Moreno T, Costela-Ruiz VJ, Montiel-Troya M, Ramos-Rodríguez JJ. Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer's Disease. Biomedicines. 2021 Dec 14;9(12):1910. [Crossref]  [PubMed]  [PMC]
  21. Yarns BC, Holiday KA, Carlson DM, Cosgrove CK, Melrose RJ. Pathophysiology of Alzheimer's Disease. Psychiatr Clin North Am. 2022 Dec;45(4):663-676. [Crossref]  [PubMed]
  22. Abubakar MB, Sanusi KO, Ugusman A, Mohamed W, Kamal H, Ibrahim NH, Khoo CS, Kumar J. Alzheimer's Disease: An Update and Insights Into Pathophysiology. Front Aging Neurosci. 2022 Mar 30;14:742408. [Crossref]  [PubMed]  [PMC]
  23. Monteiro AR, Barbosa DJ, Remião F, Silva R. Alzheimer's disease: Insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs. Biochem Pharmacol. 2023 May;211:115522. [Crossref]  [PubMed]
  24. Dhapola R, Beura SK, Sharma P, Singh SK, HariKrishnaReddy D. Oxidative stress in Alzheimer's disease: current knowledge of signaling pathways and therapeutics. Mol Biol Rep. 2024 Jan 2;51(1):48. [Crossref]  [PubMed]
  25. Walker KA, Ficek BN, Westbrook R. Understanding the Role of Systemic Inflammation in Alzheimer's Disease. ACS Chem Neurosci. 2019 Aug 21;10(8):3340-3342. [Crossref]  [PubMed]
  26. Xie J, Van Hoecke L, Vandenbroucke RE. The Impact of Systemic Inflammation on Alzheimer's Disease Pathology. Front Immunol. 2022 Jan 6;12:796867. [Crossref]  [PubMed]  [PMC]
  27. Cherbuin N, Walsh EI, Leach L, Brüstle A, Burns R, Anstey KJ, Sachdev PS, Baune BT. Systemic Inflammation Predicts Alzheimer Pathology in Community Samples without Dementia. Biomedicines. 2022 May 26;10(6):1240. [Crossref]  [PubMed]  [PMC]
  28. Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease - insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol. 2017 Sep 29;13(10):612-623. Erratum in: Nat Rev Neurol. 2017 Nov;13(11):703. [Crossref]  [PubMed]
  29. Zhang XX, Tian Y, Wang ZT, Ma YH, Tan L, Yu JT. The Epidemiology of Alzheimer's Disease Modifiable Risk Factors and Prevention. J Prev Alzheimers Dis. 2021;8(3):313-321. [Crossref]  [PubMed]
  30. Sureda A, Daglia M, Argüelles Castilla S, Sanadgol N, Fazel Nabavi S, Khan H, et al. Oral microbiota and Alzheimer's disease: Do all roads lead to Rome? Pharmacol Res. 2020 Jan;151:104582. [Crossref]  [PubMed]
  31. Liu S, Dashper SG, Zhao R. Association Between Oral Bacteria and Alzheimer's Disease: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023;91(1):129-150. [Crossref]  [PubMed]
  32. Pruntel SM, van Munster BC, de Vries JJ, Vissink A, Visser A. Oral Health as a Risk Factor for Alzheimer Disease. J Prev Alzheimers Dis. 2024;11(1):249-258. [Crossref]  [PubMed]  [PMC]
  33. Wan J, Fan H. Oral Microbiome and Alzheimer's Disease. Microorganisms. 2023 Oct 13;11(10):2550. [Crossref]  [PubMed]  [PMC]
  34. Chen J, Li T, Ye C, Zhong J, Huang JD, Ke Y, Sun H. The Lung Microbiome: A New Frontier for Lung and Brain Disease. Int J Mol Sci. 2023 Jan 21;24(3):2170. [Crossref]  [PubMed]  [PMC]
  35. Liang Y, Liu C, Cheng M, Geng L, Li J, Du W, et al. The linkbetween gut microbiome and Alzheimer's disease: From the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease. Alzheimers Dement. 2024 Aug;20(8):5771-5788. [Crossref]  [PubMed]  [PMC]
  36. Das TK, Blasco-Conesa MP, Korf J, Honarpisheh P, Chapman MR, Ganesh BP. Bacterial Amyloid Curli Associated Gut Epithelial Neuroendocrine Activation Predominantly Observed in Alzheimer's Disease Mice with Central Amyloid-β Pathology. J Alzheimers Dis. 2022;88(1):191-205. [Crossref]  [PubMed]  [PMC]
  37. Seo DO, Holtzman DM. Current understanding of the Alzheimer's disease-associated microbiome and therapeutic strategies. Exp Mol Med. 2024 Feb;56(1):86-94. [Crossref]  [PubMed]  [PMC]
  38. Liang J, Liu B, Dong X, Wang Y, Cai W, Zhang N, Zhang H. Decoding the role of gut microbiota in Alzheimer's pathogenesis and envisioning future therapeutic avenues. Front Neurosci. 2023 Sep 18;17:1242254. [Crossref]  [PubMed]  [PMC]
  39. Qu L, Li Y, Liu F, Fang Y, He J, Ma J, et al. Microbiota-Gut-Brain Axis Dysregulation in Alzheimer's Disease: Multi-Pathway Effects and Therapeutic Potential. Aging Dis. 2024 May 7;15(3):1108-1131. [Crossref]  [PubMed]  [PMC]
  40. Kowalski K, Mulak A. Brain-Gut-Microbiota Axis in Alzheimer's Disease. J Neurogastroenterol Motil. 2019 Jan 31;25(1):48-60. [Crossref]  [PubMed]  [PMC]
  41. Tarawneh R, Penhos E. The gut microbiome and Alzheimer's disease: Complex and bidirectional interactions. Neurosci Biobehav Rev. 2022 Oct;141:104814. [Crossref]  [PubMed]  [PMC]
  42. Chandra S, Sisodia SS, Vassar RJ. The gut microbiome in Alzheimer's disease: what we know and what remains to be explored. Mol Neurodegener. 2023 Feb 1;18(1):9. [Crossref]  [PubMed]  [PMC]
  43. Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, et al. Gut microbiome alterations in Alzheimer's disease. Sci Rep. 2017 Oct 19;7(1):13537. [Crossref]  [PubMed]  [PMC]
  44. Troci A, Philippen S, Rausch P, Rave J, Weyland G, Niemann K, et al. Disease- and stage-specific alterations of the oral and fecal microbiota in Alzheimer's disease. PNAS Nexus. 2023 Dec 11;3(1):pgad427. [Crossref]  [PubMed]  [PMC]
  45. He B, Sheng C, Yu X, Zhang L, Chen F, Han Y. Alterations of gut microbiota are associated with brain structural changes in the spectrum of Alzheimer's disease: the SILCODE study in Hainan cohort. Front Aging Neurosci. 2023 Jul 14;15:1216509. [Crossref]  [PubMed]  [PMC]
  46. Li H, Cui X, Lin Y, Huang F, Tian A, Zhang R. Gut microbiota changes in patients with Alzheimer's disease spectrum based on 16S rRNA sequencing: a systematic review and meta-analysis. Front Aging Neurosci. 2024 Aug 8;16:1422350. [Crossref]  [PubMed]  [PMC]
  47. Hung CC, Chang CC, Huang CW, Nouchi R, Cheng CH. Gut microbiota in patients with Alzheimer's disease spectrum: a systematic review and meta-analysis. Aging (Albany NY). 2022 Jan 14;14(1):477-496. [Crossref]  [PubMed]  [PMC]
  48. Pourahmad R, Saleki K, Zare Gholinejad M, Aram C, Soltani Farsani A, Banazadeh M, Tafakhori A. Exploring the effect of gut microbiome on Alzheimer's disease. Biochem Biophys Rep. 2024 Jul 10;39:101776. [Crossref]  [PubMed]  [PMC]
  49. Ma YY, Li X, Yu JT, Wang YJ. Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside. Transl Neurodegener. 2024 Feb 27;13(1):12. [Crossref]  [PubMed]  [PMC]
  50. Ayten Ş, Bilici S. Modulation of Gut Microbiota Through Dietary Intervention in Neuroinflammation and Alzheimer's and Parkinson's Diseases. Curr Nutr Rep. 2024 Jun;13(2):82-96. [Crossref]  [PubMed]  [PMC]
  51. Zhang T, Gao G, Kwok LY, Sun Z. Gut microbiome-targeted therapies for Alzheimer's disease. Gut Microbes. 2023 Dec;15(2):2271613. [Crossref]  [PubMed]  [PMC]
  52. Liao W, Wei J, Liu C, Luo H, Ruan Y, Mai Y, et al. Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis. Neural Regen Res. 2024 Oct 1;19(10):2281-2289. [Crossref]  [PubMed]  [PMC]
  53. Rizzi L, Rosset I, Roriz-Cruz M. Global epidemiology of dementia: Alzheimer's and vascular types. Biomed Res Int. 2014;2014:908915. [Crossref]  [PubMed]  [PMC]
  54. Bir SC, Khan MW, Javalkar V, Toledo EG, Kelley RE. Emerging Concepts in Vascular Dementia: A Review. J Stroke Cerebrovasc Dis. 2021 Aug;30(8):105864. [Crossref]  [PubMed]
  55. Iadecola C, Duering M, Hachinski V, Joutel A, Pendlebury ST, Schneider JA, Dichgans M. Vascular Cognitive Impairment and Dementia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019 Jul 2;73(25):3326-3344. [Crossref]  [PubMed]  [PMC]
  56. Inoue Y, Shue F, Bu G, Kanekiyo T. Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer's disease. Mol Neurodegener. 2023 Jul 11;18(1):46. [Crossref]  [PubMed]  [PMC]
  57. Morgan AE, Mc Auley MT. Vascular dementia: From pathobiology to emerging perspectives. Ageing Res Rev. 2024 Apr;96:102278. [Crossref]  [PubMed]
  58. Li S, Shao Y, Li K, HuangFu C, Wang W, Liu Z, Cai Z, Zhao B. Vascular Cognitive Impairment and the Gut Microbiota. J Alzheimers Dis. 2018;63(4):1209-1222. [Crossref]  [PubMed]
  59. Łuc M, Misiak B, Pawłowski M, Stańczykiewicz B, Zabłocka A, Szcześniak D, Pałęga A, Rymaszewska J. Gut microbiota in dementia. Critical review of novel findings and their potential application. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jan 10;104:110039. [Crossref]  [PubMed]
  60. Cuartero MI, García-Culebras A, Nieto-Vaquero C, Fraga E, Torres-López C, Pradillo J, Lizasoain I, Moro MÁ. The role of gut microbiota in cerebrovascular disease and related dementia. Br J Pharmacol. 2024 Mar;181(6):816-839. [Crossref]  [PubMed]
  61. Kane JPM, Surendranathan A, Bentley A, Barker SAH, Taylor JP, Thomas AJ, et al. Clinical prevalence of Lewy body dementia. Alzheimers Res Ther. 2018 Feb 15;10(1):19. [Crossref]  [PubMed]  [PMC]
  62. Prasad S, Katta MR, Abhishek S, Sridhar R, Valisekka SS, Hameed M, Kaur J, Walia N. Recent advances in Lewy body dementia: A comprehensive review. Dis Mon. 2023 May;69(5):101441. [Crossref]  [PubMed]
  63. Nelson PT, Jicha GA, Kryscio RJ, Abner EL, Schmitt FA, Cooper G, et al. Low sensitivity in clinical diagnoses of dementia with Lewy bodies. J Neurol. 2010 Mar;257(3):359-66. [Crossref]  [PubMed]  [PMC]
  64. Palmqvist S, Rossi M, Hall S, Quadalti C, Mattsson-Carlgren N, Dellavalle S, et al. Cognitive effects of Lewy body pathology in clinically unimpaired individuals. Nat Med. 2023 Aug;29(8):1971-1978. [Crossref]  [PubMed]  [PMC]
  65. McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017 Jul 4;89(1):88-100. [Crossref]  [PubMed]  [PMC]
  66. Outeiro TF, Koss DJ, Erskine D, Walker L, Kurzawa-Akanbi M, Burn D, et al. Dementia with Lewy bodies: an update and outlook. Mol Neurodegener. 2019 Jan 21;14(1):5. [Crossref]  [PubMed]  [PMC]
  67. Surendranathan A, Rowe JB, O'Brien JT. Neuroinflammation in Lewy body dementia. Parkinsonism Relat Disord. 2015 Dec;21(12):1398-406. [Crossref]  [PubMed]
  68. Loveland PM, Yu JJ, Churilov L, Yassi N, Watson R. Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review. Int J Mol Sci. 2023 Jul 28;24(15):12116. [Crossref]  [PubMed]  [PMC]
  69. Wetering JV, Geut H, Bol JJ, Galis Y, Timmermans E, Twisk JWR, et al. Neuroinflammation is associated with Alzheimer's disease co-pathology in dementia with Lewy bodies. Acta Neuropathol Commun. 2024 May 7;12(1):73. [Crossref]  [PubMed]  [PMC]
  70. Amin J, Holmes C, Dorey RB, Tommasino E, Casal YR, Williams DM, et al. Neuroinflammation in dementia with Lewy bodies: a human post-mortem study. Transl Psychiatry. 2020 Aug 3;10(1):267. [Crossref]  [PubMed]  [PMC]
  71. Ren ZL, Zhou HH, Chen CP, He H, Wang DL, Liu Z. Causal relationships between gut microbiota and dementia: A two-sample, bidirectional, Mendelian randomization study. World J Clin Cases. 2024 Jun 6;12(16):2780-2788. [Crossref]  [PubMed]  [PMC]
  72. Nishiwaki H, Ueyama J, Kashihara K, Ito M, Hamaguchi T, Maeda T, et al. Gut microbiota in dementia with Lewy bodies. NPJ Parkinsons Dis. 2022 Dec 9;8(1):169. [Crossref]  [PubMed]  [PMC]
  73. Ryman S, Vakhtin AA, Richardson SP, Lin HC. Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases. J Neurol. 2023 Feb;270(2):746-758. [Crossref]  [PubMed]  [PMC]
  74. Ulugut H, Pijnenburg YAL. Frontotemporal dementia: Past, present, and future. Alzheimers Dement. 2023 Nov;19(11):5253-5263. [Crossref]  [PubMed]
  75. Rabinovici GD, Miller BL. Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs. 2010 May;24(5):375-98. [Crossref]  [PubMed]  [PMC]
  76. Leroy M, Bertoux M, Skrobala E, Mode E, Adnet-Bonte C, Le Ber I, et al; Méotis network. Characteristics and progression of patients with frontotemporal dementia in a regional memory clinic network. Alzheimers Res Ther. 2021 Jan 8;13(1):19. [Crossref]  [PubMed]  [PMC]
  77. Antonioni A, Raho EM, Lopriore P, Pace AP, Latino RR, Assogna M, et al. Frontotemporal Dementia, Where Do We Stand? A Narrative Review. Int J Mol Sci. 2023 Jul 21;24(14):11732. [Crossref]  [PubMed]  [PMC]
  78. Mann DMA, Snowden JS. Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype. Brain Pathol. 2017 Nov;27(6):723-736. [Crossref]  [PubMed]  [PMC]
  79. Ulugut H, Dijkstra AA, Scarioni M; Netherlands Brain Bank; Barkhof F, Scheltens P, Rozemuller AJM, Pijnenburg YAL. Right temporal variant frontotemporal dementia is pathologically heterogeneous: a case-series and a systematic review. Acta Neuropathol Commun. 2021 Aug 3;9(1):131. [Crossref]  [PubMed]  [PMC]
  80. Mateo D, Marquès M, Domingo JL, Torrente M. Influence of gut microbiota on the development of most prevalent neurodegenerative dementias and the potential effect of probiotics in elderly: A scoping review. Am J Med Genet B Neuropsychiatr Genet. 2024 Mar;195(2):e32959. [Crossref]  [PubMed]
  81. Katisko K, Solje E, Korhonen P, Jääskeläinen O, Loppi S, Hartikainen P, et al. Peripheral inflammatory markers and clinical correlations in patients with frontotemporal lobar degeneration with and without the C9orf72 repeat expansion. J Neurol. 2020 Jan;267(1):76-86. [Crossref]  [PubMed]  [PMC]
  82. Chu M, Wen L, Jiang D, Liu L, Nan H, Yue A, et al. Peripheral inflammation in behavioural variant frontotemporal dementia: associations with central degeneration and clinical measures. J Neuroinflammation. 2023 Mar 8;20(1):65. [Crossref]  [PubMed]  [PMC]
  83. Trageser KJ, Smith C, Estill M, Sebastian M, Pasinetti GM. A novel gut microbiome therapeutic derived from dietary polyphenols attenuates neuroinflammation in vivo in a model of c9orf72 mediated frontotemporal dementia. Alzheimers Dement. 2020 Dec;16(S9):e046032. [Crossref]
  84. West RJH, Ugbode C, Fort-Aznar L, Sweeney ST. Neuroprotective activity of ursodeoxycholic acid in CHMP2BIntron5 models of frontotemporal dementia. Neurobiol Dis. 2020 Oct;144:105047. [Crossref]  [PubMed]  [PMC]
  85. Aerts MB, Jankovic J, van de Warrenburg BP, Bloem BR. Phenomenology, classification, and diagnostic approach to patients with movement disorders. In: Poewe W, Jankovic J, eds. Movement disorders in neurologic and systemic disease. Cambridge University Press; 2014:1-15. [Crossref]  [PubMed]
  86. Harris MK, Shneyder N, Borazanci A, Korniychuk E, Kelley RE, Minagar A. Movement disorders. Med Clin North Am. 2009 Mar;93(2):371-88, viii. [Crossref]  [PubMed]
  87. World Health Organization. Parkinson disease: a public health approach: technical brief. 2022. Available from: License: CC BYNC-SA 3.0 IGO. [Link]
  88. Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020 Jan;27(1):27-42. [Crossref]  [PubMed]
  89. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021 May;20(5):385-397. [Crossref]  [PubMed]
  90. Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, et al; PRIAMO study group. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord. 2009 Aug 15;24(11):1641-9. [Crossref]  [PubMed]
  91. Konings B, Villatoro L, Van den Eynde J, Barahona G, Burns R, McKnight M, et al. Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases. Gut. 2023 Nov;72(11):2103-2111. [Crossref]  [PubMed]
  92. Park H, Lee JY, Shin CM, Kim JM, Kim TJ, Kim JW. Chracterization of gastrointestinal disorders in patients with parkinsonian syndromes. Parkinsonism Relat Disord. 2015 May;21(5):455-60. [Crossref]  [PubMed]
  93. Simon DK, Tanner CM, Brundin P. Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology. Clin Geriatr Med. 2020 Feb;36(1):1-12. [Crossref]  [PubMed]  [PMC]
  94. Savica R, Carlin JM, Grossardt BR, Bower JH, Ahlskog JE, Maraganore DM, Bharucha AE, Rocca WA. Medical records documentation of constipation preceding Parkinson disease: A case-control study. Neurology. 2009 Nov 24;73(21):1752-8. [Crossref]  [PubMed]  [PMC]
  95. Abbott RD, Petrovitch H, White LR, Masaki KH, Tanner CM, Curb JD, et al. Frequency of bowel movements and the future risk of Parkinson's disease. Neurology. 2001 Aug 14;57(3):456-62. [Crossref]  [PubMed]
  96. Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol. 2022 Nov;22(11):657-673. [Crossref]  [PubMed]  [PMC]
  97. Oliveira LMA, Gasser T, Edwards R, Zweckstetter M, Melki R, Stefanis L, et al. Alpha-synuclein research: defining strategic moves in the battle against Parkinson's disease. NPJ Parkinsons Dis. 2021 Jul 26;7(1):65. [Crossref]  [PubMed]  [PMC]
  98. Wang L, Das U, Scott DA, Tang Y, McLean PJ, Roy S. α-synuclein multimers cluster synaptic vesicles and attenuate recycling. Curr Biol. 2014 Oct 6;24(19):2319-26. [Crossref]  [PubMed]  [PMC]
  99. Braak H, Del Tredici K, Bratzke H, Hamm-Clement J, Sandmann-Keil D, Rüb U. Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages). J Neurol. 2002 Oct;249 Suppl 3:III/1-5. [Crossref]  [PubMed]
  100. 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. [Crossref]  [PubMed]
  101. Visanji NP, Brooks PL, Hazrati LN, Lang AE. The prion hypothesis in Parkinson's disease: Braak to the future. Acta Neuropathol Commun. 2013 May 8;1:2. [Crossref]  [PubMed]  [PMC]
  102. Schmitt V, Masanetz RK, Weidenfeller M, Ebbinghaus LS, Süß P, Rosshart SP, et al. Gut-to-brain spreading of pathology in synucleinopathies: A focus on molecular signalling mediators. Behav Brain Res. 2023 Aug 24;452:114574. [Crossref]  [PubMed]
  103. Houser MC, Tansey MG. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson's disease pathogenesis? NPJ Parkinsons Dis. 2017 Jan 11;3:3. [Crossref]  [PubMed]  [PMC]
  104. Jellinger KA. Is Braak staging valid for all types of Parkinson's disease? J Neural Transm (Vienna). 2019 Apr;126(4):423-431. [Crossref]  [PubMed]
  105. Ulusoy A, Musgrove RE, Rusconi R, Klinkenberg M, Helwig M, Schneider A, Di Monte DA. Neuron-to-neuron α-synuclein propagation in vivo is independent of neuronal injury. Acta Neuropathol Commun. 2015 Mar 24;3:13. [Crossref]  [PubMed]  [PMC]
  106. Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Björklund T, et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014 Dec;128(6):805-20. [Crossref]  [PubMed]
  107. Uemura N, Yagi H, Uemura MT, Hatanaka Y, Yamakado H, Takahashi R. Inoculation of α-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve. Mol Neurodegener. 2018 May 11;13(1):21. Erratum in: Mol Neurodegener. 2019 Jul 26;14(1):31. [Crossref]  [PubMed]  [PMC]
  108. Svensson E, Horváth-Puhó E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P, Sørensen HT. Vagotomy and subsequent risk of Parkinson's disease. Ann Neurol. 2015 Oct;78(4):522-9. [Crossref]  [PubMed]
  109. Arotcarena ML, Dovero S, Prigent A, Bourdenx M, Camus S, Porras G, et al. Bidirectional gut-to-brain and brain-togut propagation of synucleinopathy in non-human primates. Brain. 2020 May 1;143(5):1462-1475. [Crossref]  [PubMed]
  110. Sumikura H, Takao M, Hatsuta H, Ito S, Nakano Y, Uchino A, et al. Distribution of α-synuclein in the spinal cord and dorsal root ganglia in an autopsy cohort of elderly persons.Acta Neuropathol Commun. 2015 Sep 15;3:57. [Crossref]  [PubMed]  [PMC]
  111. Liu Z, Chan RB, Cai Z, Liu X, Wu Y, Yu Z, et al. α-Synuclein-containing erythrocytic extracellular vesicles: essential contributors to hyperactivation of monocytes in Parkinson's disease. J Neuroinflammation. 2022 Feb 22;19(1):53. [Crossref]  [PubMed]  [PMC]
  112. Al-Asmakh M, Hedin L. Microbiota and the control of blood-tissue barriers. Tissue Barriers. 2015 May 29;3(3):e1039691. [Crossref]  [PubMed]  [PMC]
  113. Barnhart MM, Chapman MR. Curli biogenesis and function. Annu Rev Microbiol. 2006;60:131-47. [Crossref]  [PubMed]  [PMC]
  114. Chen SG, Stribinskis V, Rane MJ, Demuth DR, Gozal E, Roberts AM, 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 Oct 6;6:34477. [Crossref]  [PubMed]  [PMC]
  115. Sampson TR, Challis C, Jain N, Moiseyenko A, Ladinsky MS, Shastri GG, et al. A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice. Elife. 2020 Feb 11;9:e53111. [Crossref]  [PubMed]  [PMC]
  116. Haikal C, Ortigosa-Pascual L, Najarzadeh Z, Bernfur K, Svanbergsson A, Otzen DE, Linse S, Li JY. The Bacterial Amyloids Phenol Soluble Modulins from Staphylococcus aureus Catalyze Alpha-Synuclein Aggregation. Int J Mol Sci. 2021 Oct 27;22(21):11594. [Crossref]  [PubMed]  [PMC]
  117. Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord. 2015 Mar;30(3):350-8. [Crossref]  [PubMed]
  118. Sakata T. Stimulatory effect of short-chain fatty acids on epithelial cell proliferation in the rat intestine: a possible explanation for trophic effects of fermentable fibre, gut microbes and luminal trophic factors. Br J Nutr. 1987 Jul;58(1):95-103. [Crossref]  [PubMed]
  119. Soret R, Chevalier J, De Coppet P, Poupeau G, Derkinderen P, Segain JP, Neunlist M. Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. Gastroenterology. 2010 May;138(5):1772-82. [Crossref]  [PubMed]
  120. Keshavarzian A, Engen P, Bonvegna S, Cilia R. The gut microbiome in Parkinson's disease: A culprit or a bystander? Prog Brain Res. 2020;252:357-450. [Crossref]  [PubMed]
  121. Aho VTE, Houser MC, Pereira PAB, Chang J, Rudi K, Paulin L, et al. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease. Mol Neurodegener. 2021 Feb 8;16(1):6. [Crossref]  [PubMed]  [PMC]
  122. Chen SJ, Chen CC, Liao HY, Lin YT, Wu YW, Liou JM, et al. Association of Fecal and Plasma Levels of ShortChain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease. Neurology. 2022 Feb 22;98(8):e848-e858. [Crossref]
  123. Julio-Pieper M, Bravo JA, Aliaga E, Gotteland M. Review article: intestinal barrier dysfunction and central nervous system disorders--a controversial association. Aliment Pharmacol Ther. 2014 Nov;40(10):1187-201. [Crossref]  [PubMed]
  124. Salat-Foix D, Tran K, Ranawaya R, Meddings J, Suchowersky O. Increased intestinal permeability and Parkinson disease patients: chicken or egg? Can J Neurol Sci. 2012 Mar;39(2):185-8. [Crossref]  [PubMed]
  125. Buckley A, Turner JR. Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease. Cold Spring Harb Perspect Biol. 2018 Jan 2;10(1):a029314. [Crossref]  [PubMed]  [PMC]
  126. Babacan Yildiz G, Kayacan ZC, Karacan I, Sumbul B, Elibol B, Gelisin O, Akgul O. Altered gut microbiota in patients with idiopathic Parkinson's disease: an age-sex matched case-control study. Acta Neurol Belg. 2023 Jun;123(3):999-1009. [Crossref]  [PubMed]
  127. Bunnett NW. Neuro-humoral signalling by bile acids and the TGR5 receptor in the gastrointestinal tract. J Physiol. 2014 Jul 15;592(14):2943-50. [Crossref]  [PubMed]  [PMC]
  128. Li P, Killinger BA, Ensink E, Beddows I, Yilmaz A, Lubben N, et al. Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson's Disease. Metabolites. 2021 Jan 4;11(1):29. [Crossref]  [PubMed]  [PMC]
  129. Bai F, You L, Lei H, Li X. Association between increased and decreased gut microbiota abundance and Parkinson's disease: A systematic review and subgroup meta-analysis. Exp Gerontol. 2024 Jun 15;191:112444. [Crossref]  [PubMed]
  130. Lin CH, Chen CC, Chiang HL, Liou JM, Chang CM, Lu TP, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease. J Neuroinflammation. 2019 Jun 27;16(1):129. [Crossref]  [PubMed]  [PMC]
  131. Zhou S, Li B, Deng Y, Yi J, Mao G, Wang R, et al. Meta-analysis of the relations between gut microbiota and pathogens and Parkinson's disease. Adv Clin Exp Med. 2023 Jun;32(6):613-621. [Crossref]  [PubMed]
  132. Van Felius ID, Akkermans LM, Bosscha K, Verheem A, Harmsen W, Visser MR, Gooszen HG. Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis. Neurogastroenterol Motil. 2003 Jun;15(3):267-76. [Crossref]  [PubMed]
  133. Hirayama M, Ohno K. Parkinson's Disease and Gut Microbiota. Ann Nutr Metab. 2021;77 Suppl 2:28-35. [Crossref]  [PubMed]
  134. Romano S, Savva GM, Bedarf JR, Charles IG, Hildebrand F, Narbad A. Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation. NPJ Parkinsons Dis. 2021 Mar 10;7(1):27. [Crossref]  [PubMed]  [PMC]
  135. van Kessel SP, Auvinen P, Scheperjans F, El Aidy S. Gut bacterial tyrosine decarboxylase associates with clinical variables in a longitudinal cohort study of Parkinsons disease. NPJ Parkinsons Dis. 2021 Dec 15;7(1):115. [Crossref]  [PubMed]  [PMC]
  136. Bruggeman A, Vandendriessche C, Hamerlinck H, De Looze D, Tate DJ, Vuylsteke M, et al. Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial. EClinicalMedicine. 2024 Mar 27;71:102563. [Crossref]  [PubMed]  [PMC]
  137. Tesauro M, Bruschi M, Filippini T, D'Alfonso S, Mazzini L, Corrado L, et al. Metal(loid)s role in the pathogenesis of amyotrophic lateral sclerosis: Environmental, epidemiological, and genetic data. Environ Res. 2021 Jan;192:110292. [Crossref]  [PubMed]
  138. Pupillo E, Bianchi E, Chiò A, Casale F, Zecca C, Tortelli R, Beghi E; SLALOM Group; PARALS Group; SLAP Group. Amyotrophic lateral sclerosis and food intake. Amyotroph Lateral Scler Frontotemporal Degener. 2018 May;19(3- 4):267-274. [Crossref]  [PubMed]
  139. De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Bäckhed F, Mithieux G. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014 Jan 16;156(1-2):84-96. [Crossref]  [PubMed]
  140. Brenner SR. Blue-green algae or cyanobacteria in the intestinal micro-flora may produce neurotoxins such as Beta-N-Methylamino-L-Alanine (BMAA) which may be related to development of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson-Dementia-Complex in humans and Equine Motor Neuron Disease in horses. Med Hypotheses. 2013 Jan;80(1):103. [Crossref]  [PubMed]
  141. Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF. Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. J Neuroinflammation. 2019 Mar 1;16(1):53. [Crossref]  [PubMed]  [PMC]
  142. Longstreth WT Jr, Meschke JS, Davidson SK, Smoot LM, Smoot JC, Koepsell TD. Hypothesis: a motor neuron toxin produced by a clostridial species residing in gut causes ALS. Med Hypotheses. 2005;64(6):1153-6. [Crossref]  [PubMed]
  143. Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467. [Crossref]  [PubMed]  [PMC]
  144. Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017 Feb;20(2):145-155. [Crossref]  [PubMed]  [PMC]
  145. Blacher E, Bashiardes S, Shapiro H, Rothschild D, Mor U, Dori-Bachash M, et al. Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature. 2019 Aug;572(7770):474-480. [Crossref]  [PubMed]
  146. Smith EF, Shaw PJ, De Vos KJ. The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett. 2019 Sep 25;710:132933. [Crossref]  [PubMed]
  147. Murch SJ, Cox PA, Banack SA, Steele JC, Sacks OW. Occurrence of beta-methylamino-l-alanine (BMAA) in ALS/PDC patients from Guam. Acta Neurol Scand. 2004 Oct;110(4):267-9. [Crossref]  [PubMed]
  148. Adesso S, Ruocco M, Rapa SF, Piaz FD, Raffaele Di Iorio B, Popolo A, et al. Effect of Indoxyl Sulfate on the Repair and Intactness of Intestinal Epithelial Cells: Role of Reactive Oxygen Species' Release. Int J Mol Sci. 2019 May 8;20(9):2280. [Crossref]  [PubMed]  [PMC]
  149. Fennema D, Phillips IR, Shephard EA. Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease. Drug Metab Dispos. 2016 Nov;44(11):1839-1850. Erratum in: Drug Metab Dispos. 2016 Dec;44(12):1949. [Crossref]  [PubMed]  [PMC]
  150. Szende B, Tyihák E. Effect of formaldehyde on cell proliferation and death. Cell Biol Int. 2010 Dec;34(12):1273-82. [Crossref]  [PubMed]
  151. Dickerson AS, Hansen J, Gredal O, Weisskopf MG. Amyotrophic Lateral Sclerosis and Exposure to Diesel Exhaust in a Danish Cohort. Am J Epidemiol. 2018 Aug 1;187(8):1613-1622. [Crossref]  [PubMed]  [PMC]
  152. Ash PEA, Stanford EA, Al Abdulatif A, Ramirez-Cardenas A, Ballance HI, Boudeau S, et al. Dioxins and related environmental contaminants increase TDP-43 levels. Mol Neurodegener. 2017 May 5;12(1):35. [Crossref]  [PubMed]  [PMC]
  153. Gao D, Wu M, Wang C, Wang Y, Zuo Z. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio). Aquat Toxicol. 2015 Oct;167:200-8. [Crossref]  [PubMed]
  154. Béland LC, Markovinovic A, Jakovac H, De Marchi F, Bilic E, Mazzini L, Kriz J, Munitic I. Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient immune responses. Brain Commun. 2020 Aug 13;2(2):fcaa124. [Crossref]  [PubMed]  [PMC]
  155. Shi N, Li N, Duan X, Niu H. Interaction between the gut microbiome and mucosal immune system. Mil Med Res. 2017 Apr 27;4:14. [Crossref]  [PubMed]  [PMC]
  156. Maynard CL, Elson CO, Hatton RD, Weaver CT. Reciprocal interactions of the intestinal microbiota and immune system. Nature. 2012 Sep 13;489(7415):231-41. [Crossref]  [PubMed]  [PMC]
  157. Mazzini L, De Marchi F, Niccolai E, Mandrioli J, Amedei A. Gastrointestinal Status and Microbiota Shaping in Amyotrophic Lateral Sclerosis: A New Frontier for Targeting? In: Araki T, editor. Amyotrophic Lateral Sclerosis [Internet]. Brisbane (AU): Exon Publications; 2021 Jul 25. Chapter 8. [Crossref]  [PubMed]
  158. Kouchaki E, Tamtaji OR, Salami M, Bahmani F, Daneshvar Kakhaki R, Akbari E, Tajabadi-Ebrahimi M, Jafari P, Asemi Z. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2017 Oct;36(5):1245-1249. [Crossref]  [PubMed]
  159. Akbari E, Asemi Z, Daneshvar Kakhaki R, Bahmani F, Kouchaki E, Tamtaji OR, Hamidi GA, Salami M. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial. Front Aging Neurosci. 2016 Nov 10;8:256. [Crossref]  [PubMed]  [PMC]
  160. Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R, Kouchaki E, Bahmani F, Borzabadi S, 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 Jun;38(3):1031-1035.  [Crossref]  [PubMed]
  161. Wu S, Yi J, Zhang YG, Zhou J, Sun J. Leaky intestine and impaired microbiome in an amyotrophic lateral sclerosis mouse model. Physiol Rep. 2015 Apr;3(4):e12356. [Crossref]  [PubMed]  [PMC]
  162. Zhang YG, Wu S, Yi J, Xia Y, Jin D, Zhou J, Sun J. Target Intestinal Microbiota to Alleviate Disease Progression in Amyotrophic Lateral Sclerosis. Clin Ther. 2017 Feb;39(2):322-336. [Crossref]  [PubMed]  [PMC]
  163. Burberry A, Wells MF, Limone F, Couto A, Smith KS, Keaney J, et al. C9orf72 suppresses systemic and neural inflammation induced by gut bacteria. Nature. 2020 Jun;582(7810):89-94. [Crossref]  [PubMed]  [PMC]
  164. Mazzini L, Mogna L, De Marchi F, Amoruso A, Pane M, Aloisio I, et al. Potential Role of Gut Microbiota in ALSPathogenesis and Possible Novel Therapeutic Strategies. J Clin Gastroenterol. 2018 Nov/Dec;52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017:S68-S70. [Crossref]  [PubMed]
  165. Di Gioia D, Bozzi Cionci N, Baffoni L, Amoruso A, Pane M, Mogna L, et al. A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis. BMC Med. 2020 Jun 17;18(1):153. [Crossref]  [PubMed]  [PMC]
  166. Rowin J, Xia Y, Jung B, Sun J. Gut inflammation and dysbiosis in human motor neuron disease. Physiol Rep. 2017 Sep;5(18):e13443. [Crossref]  [PubMed]  [PMC]
  167. Nicholson K, Bjornevik K, Abu-Ali G, Chan J, Cortese M, Dedi B, et al. The human gut microbiota in people with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2021 May;22(3-4):186-194. [Crossref]  [PubMed]
  168. Willing BP, Russell SL, Finlay BB. Shifting the balance: antibiotic effects on host-microbiota mutualism. Nat Rev Microbiol. 2011 Apr;9(4):233-43. [Crossref]  [PubMed]
  169. Mandrioli J, Amedei A, Cammarota G, Niccolai E, Zucchi E, D'Amico R, et al. FETR-ALS Study Protocol: A Randomized Clinical Trial of Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis. Front Neurol. 2019 Sep 20;10:1021. [Crossref]  [PubMed]  [PMC]
  170. Zarate CA, Manji HK. Riluzole in psychiatry: a systematic review of the literature. Expert Opin Drug Metab Toxicol. 2008 Sep;4(9):1223-34. [Crossref]  [PubMed]  [PMC]