Is Parkinson’s disease a chronic low-grade inflammatory bowel disease?

  • Malvyne Rolli-Derkinderen
  • Laurène Leclair-Visonneau
  • Arnaud Bourreille
  • Emmanuel Coron
  • Michel Neunlist
  • Pascal DerkinderenEmail author


While the pathogenesis of Parkinson’s disease is not fully understood, there is increasing evidence that inflammatory responses in the brain are implicated in both disease initiation and progression. The inflammatory process in Parkinson’s disease is, however, not limited to the brain but also involves the gastrointestinal tract. High amounts of cytokines and inflammatory markers are found in the colon of Parkinson’s disease patients and there is now strong epidemiological and genetical evidence linking Parkinson’s disease to inflammatory bowel diseases. Recent findings obtained in both experimental inflammatory bowel diseases and Parkinson’s disease further support a bidirectional link between gastrointestinal inflammation and brain neurodegeneration. Altogether, these observations suggest a role for gastrointestinal inflammation in the initiation and progression of Parkinson’s disease.


Parkinson’s disease Inflammatory bowel disease Crohn’s disease Ulcerative colitis Enteric nervous system LRRK2 



Work in our laboratory was supported by Institut de France (Fondation NRJ), France Parkinson, CECAP (Comité d’Entente et de Coordination des Associations de Parkinsoniens), ADPLA (Association des Parkinsoniens de Loire Atlantique), FFPG (Fédération française des groupements parkinsoniens) and Parkinsoniens de Vendée.

Compliance with ethical standards

Conflicts of interest

The authors report no disclosure relevant to the research covered in this article.


  1. 1.
    Chapelet G, Leclair-Visonneau L, Clairembault T et al (2018) Can the gut be the missing piece in uncovering PD pathogenesis? Parkinsonism Relat Disord. Google Scholar
  2. 2.
    Edwards LL, Quigley EM, Pfeiffer RF (1992) Gastrointestinal dysfunction in Parkinson’s disease: frequency and pathophysiology. Neurology 42:726–732CrossRefGoogle Scholar
  3. 3.
    Beach TG, Adler CH, Sue LI et al (2010) Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119:689–702. CrossRefGoogle Scholar
  4. 4.
    Gelpi E, Navarro-Otano J, Tolosa E et al (2014) Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Mov Disord 29:1010–1018. CrossRefGoogle Scholar
  5. 5.
    Wakabayashi K, Takahashi H, Takeda S et al (1988) Parkinson’s disease: the presence of Lewy bodies in Auerbach’s and Meissner’s plexuses. Acta Neuropathol 76:217–221CrossRefGoogle Scholar
  6. 6.
    Bialecka M, Kurzawski M, Klodowska-Duda G et al (2007) CARD15 variants in patients with sporadic Parkinson’s disease. Neurosci Res 57:473–476. CrossRefGoogle Scholar
  7. 7.
    Maeda S, Hsu L-C, Liu H et al (2005) Nod2 mutation in Crohn’s disease potentiates NF-kappaB activity and IL-1beta processing. Science 307:734–738. CrossRefGoogle Scholar
  8. 8.
    Umeno J, Asano K, Matsushita T et al (2011) Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 17:2407–2415. CrossRefGoogle Scholar
  9. 9.
    Hui KY, Fernandez-Hernandez H, Hu J et al (2018) Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease. Sci Transl Med. Google Scholar
  10. 10.
    Bihari K, Lees AJ (1987) Cigarette smoking, Parkinson’s disease and ulcerative colitis. J Neurol Neurosurg Psychiatry 50:635CrossRefGoogle Scholar
  11. 11.
    Fujioka S, Curry SE, Kennelly KD et al (2017) Occurrence of Crohn’s disease with Parkinson’s disease. Parkinsonism Relat Disord 37:116–117. CrossRefGoogle Scholar
  12. 12.
    Lin J-C, Lin C-S, Hsu C-W et al (2016) Association between parkinson’s disease and inflammatory bowel disease: a Nationwide Taiwanese Retrospective Cohort Study. Inflamm Bowel Dis 22:1049–1055. CrossRefGoogle Scholar
  13. 13.
    Peter I, Dubinsky M, Bressman S et al (2018) Anti-tumor necrosis factor therapy and incidence of parkinson disease among patients with inflammatory bowel disease. JAMA Neurol. Google Scholar
  14. 14.
    Villumsen M, Aznar S, Pakkenberg B et al (2018) Inflammatory bowel disease increases the risk of Parkinson’s disease: a Danish nationwide cohort study 1977–2014. Gut. Google Scholar
  15. 15.
    Weimers P, Halfvarson J, Sachs MC et al (2019) Inflammatory bowel disease and Parkinson’s disease: a Nationwide Swedish Cohort Study. Inflamm Bowel Dis 25:111–123. CrossRefGoogle Scholar
  16. 16.
    Zhu F, Li C, Gong J et al (2019) The risk of Parkinson’s disease in inflammatory bowel disease: a systematic review and meta-analysis. Dig Liver Dis 51:38–42. CrossRefGoogle Scholar
  17. 17.
    Marras C, Lang AE, Austin PC et al (2016) Appendectomy in mid and later life and risk of Parkinson’s disease: a population-based study. Mov Disord 31:1243–1247. CrossRefGoogle Scholar
  18. 18.
    Mendes A, Gonçalves A, Vila-Chã N et al (2015) Appendectomy may delay Parkinson’s disease onset. Mov Disord 30:1404–1407. CrossRefGoogle Scholar
  19. 19.
    Palacios N, Hughes KC, Cereda E et al (2018) Appendectomy and risk of Parkinson’s disease in two large prospective cohorts of men and women. Mov Disord 33:1492–1496. CrossRefGoogle Scholar
  20. 20.
    Yilmaz R, Bayram E, Ulukan Ç et al (2017) Appendectomy history is not related to Parkinson’s disease. J Parkinsons Dis 7:347–352. CrossRefGoogle Scholar
  21. 21.
    Svensson E, Horváth-Puhó E, Stokholm MG et al (2016) Appendectomy and risk of Parkinson’s disease: a nationwide cohort study with more than 10 years of follow-up. Mov Disord 31:1918–1922. CrossRefGoogle Scholar
  22. 22.
    Killinger BA, Madaj Z, Sikora JW et al (2018) The vermiform appendix impacts the risk of developing Parkinson’s disease. Sci Transl Med. Google Scholar
  23. 23.
    Altschuler SM, Escardo J, Lynn RB, Miselis RR (1993) The central organization of the vagus nerve innervating the colon of the rat. Gastroenterology 104:502–509CrossRefGoogle Scholar
  24. 24.
    Gray MT, Munoz DG, Gray DA et al (2014) Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects. Mov Disord 29:991–998. CrossRefGoogle Scholar
  25. 25.
    Russel MG, Dorant E, Brummer RJ et al (1997) Appendectomy and the risk of developing ulcerative colitis or Crohn’s disease: results of a large case-control study. South Limburg Inflammatory Bowel Disease Study Group. Gastroenterology 113:377–382CrossRefGoogle Scholar
  26. 26.
    Devos D, Lebouvier T, Lardeux B et al (2013) Colonic inflammation in Parkinson’s disease. Neurobiol Dis 50:42–48. CrossRefGoogle Scholar
  27. 27.
    Pochard C, Leclair-Visonneau L, Coron E et al (2018) Cyclooxygenase 2 is upregulated in the gastrointestinal tract in Parkinson’s disease. Mov Disord 33:493–494. CrossRefGoogle Scholar
  28. 28.
    Perez-Pardo P, Dodiya HB, Engen PA et al (2018) Role of TLR4 in the gut-brain axis in Parkinson’s disease: a translational study from men to mice. Gut. Google Scholar
  29. 29.
    Eeckhaut V, Machiels K, Perrier C et al (2013) Butyricicoccus pullicaecorum in inflammatory bowel disease. Gut 62:1745–1752. CrossRefGoogle Scholar
  30. 30.
    Houser MC, Chang J, Factor SA et al (2018) Stool immune profiles evince gastrointestinal inflammation in Parkinson’s disease. Mov Disord 33:793–804. CrossRefGoogle Scholar
  31. 31.
    Schwiertz A, Spiegel J, Dillmann U et al (2018) Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson’s disease. Parkinsonism Relat Disord. Google Scholar
  32. 32.
    Eichele DD, Kharbanda KK (2017) Dextran sodium sulfate colitis murine model: an indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World J Gastroenterol 23:6016–6029. CrossRefGoogle Scholar
  33. 33.
    Villarán RF, Espinosa-Oliva AM, Sarmiento M et al (2010) Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson’s disease. J Neurochem 114:1687–1700. CrossRefGoogle Scholar
  34. 34.
    Garrido-Gil P, Rodriguez-Perez AI, Dominguez-Meijide A et al (2018) Bidirectional neural interaction between central dopaminergic and gut lesions in Parkinson’s disease models. Mol Neurobiol. Google Scholar
  35. 35.
    Blandini F, Armentero M-T, Martignoni E (2008) The 6-hydroxydopamine model: news from the past. Parkinsonism Relat Disord 14(Suppl 2):S124–S129. CrossRefGoogle Scholar
  36. 36.
    Pellegrini C, Fornai M, Colucci R et al (2016) Alteration of colonic excitatory tachykininergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration. J Neuroinflamm 13:146. CrossRefGoogle Scholar
  37. 37.
    Zheng L-F, Wang Z-Y, Li X et al (2011) Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson’s disease. Brain Res 1420:59–67. CrossRefGoogle Scholar
  38. 38.
    Lema Tomé CM, Tyson T, Rey NL et al (2013) Inflammation and α-synuclein’s prion-like behavior in Parkinson’s disease—is there a link? Mol Neurobiol 47:561–574. CrossRefGoogle Scholar
  39. 39.
    Houser MC, Tansey MG (2017) The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis 3:3. CrossRefGoogle Scholar
  40. 40.
    Walter GC, Phillips RJ, Baronowsky EA, Powley TL (2009) Versatile, high-resolution anterograde labeling of vagal efferent projections with dextran amines. J Neurosci Methods 178:1–9. CrossRefGoogle Scholar
  41. 41.
    Liu B, Fang F, Pedersen NL et al (2017) Vagotomy and Parkinson disease: a Swedish register-based matched-cohort study. Neurology 88:1996–2002. CrossRefGoogle Scholar
  42. 42.
    Svensson E, Horváth-Puhó E, Thomsen RW et al (2015) Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol 78:522–529. CrossRefGoogle Scholar
  43. 43.
    Prigent A, Lionnet A, Durieu E et al (2019) Enteric alpha-synuclein expression is increased in Crohn’s disease. Acta Neuropathol 137:359–361. CrossRefGoogle Scholar
  44. 44.
    Prigent A, Gonzales J, Durand T et al (2018) Acute inflammation down-regulates alpha-synuclein expression in enteric neurons. J Neurochem. Google Scholar
  45. 45.
    Guan Q, Zhang J (2017) Recent advances: the imbalance of cytokines in the pathogenesis of inflammatory bowel disease. Mediat Inflamm 2017:4810258. Google Scholar
  46. 46.
    Fedorova TD, Seidelin LB, Knudsen K et al (2017) Decreased intestinal acetylcholinesterase in early Parkinson disease: an 11C-donepezil PET study. Neurology 88:775–781. CrossRefGoogle Scholar
  47. 47.
    Greenland JC, Williams-Gray CH, Barker RA (2019) The clinical heterogeneity of Parkinson’s disease and its therapeutic implications. Eur J Neurosci 49:328–338. CrossRefGoogle Scholar
  48. 48.
    Johnson ME, Stecher B, Labrie V et al (2019) Triggers, facilitators, and aggravators: redefining Parkinson’s disease pathogenesis. Trends Neurosci 42:4–13. CrossRefGoogle Scholar
  49. 49.
    Zou W, Pu T, Feng W et al (2019) Blocking meningeal lymphatic drainage aggravates Parkinson’s disease-like pathology in mice overexpressing mutated α-synuclein. Transl Neurodegener 8:7. CrossRefGoogle Scholar
  50. 50.
    Takagawa T, Kitani A, Fuss I et al (2018) An increase in LRRK2 suppresses autophagy and enhances Dectin-1-induced immunity in a mouse model of colitis. Sci Transl Med. Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Inserm, U1235NantesFrance
  2. 2.University NantesNantesFrance
  3. 3.CHU Nantes, Institut des Maladies de l’Appareil DigestifNantesFrance
  4. 4.Department of PhysiologyCHU NantesNantesFrance
  5. 5.Department of NeurologyCHU NantesNantesFrance

Personalised recommendations