MetaBiom
Microbiome & Chronic Diseases

Evidence Based Medicine

Parkinson's Disease {40000200}

Record Keys
Definition:
Parkinson's Disease
Class:[  ]

Details
Other Terms:
PD
Authoring date:
2021-02-05

Links

Meta Information
ICD:[  ]
Category:
Neurologic
MedDra ID:
10061536
MedDra Level:
pt

Notes

- Bile > Clostridium located in appendix and Ileum > toxic bile acids > Triggering, Deteriorating PD
- PD is less frequent (~ 20%) in Appendectomy cases
- Cases of Roux-Y operation who developed PD
May other GI blind-loop-like structures:
-Increased incidence by aging parallel to Parkinson’s disease: Fistula (IBD), Diverticulosis, chronic Cholecystic, chronic appendicitis, …
-Induced blind loop structures: Roux-Y, other GI blind loop anastomoses
predispose to PD development in a similar way?

If yes, how can we target related treatments?
- Correcting surgical methods?
- Early correction of chronic structural GI diseases?
- Administration of specific substances to detoxify toxic bile acids?
- Aiming the responsible Clostridium Species (Other Microbiota ?) with specific antibiotics/ intraluminal antibodies and/or Phages.
- Creating a competitive environment by other beneficial Microbiota particularly Lactobacillus which can be considered as a possible preventive measure against parkinson's disease.
- It has been newly related to toxic bile acids produced by some clostridia species. {https://www.metabiom.org/panel?mid=oreferences&id=1626}

Shared Notes

  • [1.28] 
    - Gut-to-brain propagation of pathologic α-synuclein via the vagus nerve causes PD
    - Dopamine neurons degenerate in the pathologic α-synuclein gut-to-brain model of PD
    - Gut injection of pathologic α-synuclein causes PD-like motor and non-motor symptoms
    - PD-like pathology and symptoms require endogenous α-synuclein.
  • [1.29] 
    - The most common bacteria found in the stool samples are: Bacteroides, Faecalibacerium, Gemmiger, Roseburia, Prevotella, and Ruminococcus.
    - Severe constipation > Decreased Faecalibacterium.
    - Lowest physical activity and severe constipation > Increased Firmicutes
    - High physical activity > Increased Bacteroides.
  • [1.30] 
    - The gastrointestinal tract is the major site for L-dopa decarboxylation
    - L-dopa > decarboxylation > generation of dopamine in the periphery > cannot cross the blood-brain barrier and causes unwanted side effects.
    - L-dopa is coadministered with drugs that block peripheral metabolism, including the AADC inhibitor carbidopa.
    - Even with carbidopa, up to 56% of L-dopa fails to reach the brain.
    - Enterococcus faecalis (enzyme (PLP-dependent tyrosine decarboxylase or TyrDC)) consume dopamine > producing meta-tyramine as a by-product > may contribute to some of the noxious L-dopa side effects.
    - carbidopa may not be able to penetrate the microbial cells or the slight structural variance could prevent the drug from interacting with the bacterial enzyme.
  • [1.31] 
    - The relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients.
    - Severe patients exhibited elevated levels of Verrucomicrobiae.
    - High levels of Verrucomicrobiae in the severe PD may increase intestinal leakiness, facilitating translocation of luminal LPS to the enteric nervous system or systemic circulation.
    - Systemic LPS has been linked to intestinal inflammation, which in turn is associated with enteric Thy1-αSyn aggregation.
  • [1.32] 
    - Patients with inflammatory bowel disease are more likely to develop Parkinson disease.
    - People receiving drugs used to reduce inflammation—tumor necrosis factor (TNF) inhibitors—the incidence of the neurodegenerative disease dropped significantly.
    - Chronically inflamed gut may elevate alpha-synuclein levels locally and give rise to inflammation throughout the body, which in itself could increase the permeability of the gut and blood-brain barriers.
    - Circulating cytokines are increased that can promote inflammation.
  • [1.33] 
    - Overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus.
  • [1.34] 
    - There is a lower fungal DNA relative to bacterial DNA among PD patients.
    - No fungi differed in abundance.
    - No fungi association with motor, cognitive, or gastrointestinal features among PD patients.
  • [1.35] 
    - Later age of onset correlated most strongly with MIND diet (Mediterranean diet and the DASH "Dietary Approaches to Stop Hypertension" diet) adherence in the females PD Patient
    - Greek Mediterranean adherence is associated with later PD onset
  • [1.21] 
    - FABP6 (fatty acid binding protein 6) is the intracellular bile acid transporter which returns bile acids to enterohepatic circulation.
    - In Parkinson Disease, ileum and appendix had a strong decrease in fatty acid binding protein 6 (FABP6) and a decrease in lipid metabolism.
    - Primary bile acids or total bile acid levels in the PD appendix are not changed.
    - Secondary bile acids produced by the microbiota are elevated PD appendix.
  • [1.36] 
    Toxic Bile acids produced by specifics Clostridium species may predispose to PD
  • [1.37] 
    - PD is not one, but two diseases.
    - Some patients had damage to the brains dopamine system before damage in the intestines and heart occurred.
    - In other patients, scans revealed damage to the nervous systems of the intestines and heart before the damage in the brains dopamine system was visible
  • [1.38] 
    - PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson’s disease
    - The infection of mice that did not express PINK1 and/or PRKN with the Gram-negative bacterium Citrobacter rodentium triggered mitochondrial antigen presentation in the periphery. Furthermore, the intestinal infection led to cytotoxic CD8+ T cells being established, which targeted dopaminergic neurons in the brain, whereas non-dopaminergic neurons were not affected
  • [1.27] 
    - The relative abundance of Enterobacteriaceae is positively associated with the severity of postural instability and gait difficulty.
  • [1.25] 
    - Increase of D-Laktat und Glykolat has amelorative effects on Parkinson disease.
    - D-Laktat is produced by lactobacillus bulgaricus.
  • [1.39] 
    - In 1817, the English surgeon James Parkinson described some of the first cases of the “shaking palsy” that would come to be known as Parkinson’s disease.
    - One individual had developed numbness and prickling sensations in both arms. Parkinson noticed that the man’s abdomen seemed to contain “considerable accumulation”. He dosed the man with a laxative, and ten days later his bowels were empty and his symptoms were gone.

Common References