Is Parkinson´s Disease a gastrointestinal disorder, with microbiota contribution?

The pathomechanism of Parkinson´s disease (PD) is well known but its origin is far from completely understood. The fact that among the prodromal signs of PD are constipation and a number of other (autonomically regulated) symptoms that occur years before the onset of movement disorders has given rise to the idea that a peripheral origin may exist. Since a-synuclein inclusions are found not only in the central nervous system (CNS) but also in the enteric nervous system (ENS) of the gut (1), Brack et al. proposed some 10 years ago that they may enter the human body via the gastrointestinal tract. It was recently shown that they, in fact, can travel backwards from the stomach wall to the brain when induced experimentally in animals (2). This opened the door to the discussion of whether a microbiota contribution to PD may exist that triggers local inflammation and increases gut permeability (3). It has been hypothesized that enteric glial cells may play a key role here (4). A novel paper (see  F. Scheperjans post) now shows for the first time that the gut microbiota of PD patients can be distinguished from that of healthy subjects (5), and that this is related to both the symptom severity, e.g. of constipation, as well as the clinical phenotype of PD.

References

  1. 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.
  2. Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Björklund T, Wang ZY, Roybon L, Melki R, Li JY. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014 Dec;128(6):805-20.
  3. Goldman SM, Kamel F, Ross GW, Jewell SA, Marras C, Hoppin JA, Umbach DM, Bhudhikanok GS, Meng C, Korell M, Comyns K, Hauser RA, Jankovic J, Factor SA, Bressman S, Lyons KE, Sandler DP, Langston JW, Tanner CM. Peptidoglycan recognition protein genes and risk of Parkinson’s disease. Mov Disord. 2014 Aug;29(9):1171-80.
  4. Clairembault T, Leclair-Visonneau L, Neunlist M, Derkinderen P. Enteric glial cells: New players in Parkinson’s disease? Mov Disord. 2014 Aug 7. doi:10.1002/mds.25979.
  5. 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. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord. 2014 Dec 5. doi: 10.1002/mds.26069.
Paul Enck
Paul Enck
Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.