MetaBiom
Microbiome & Chronic Diseases

Evidence Based Medicine

Parkinson Disease {40000103}

Record Keys


Definition:
Parkinson Disease
Class:[  ]

Details


Other Terms:
PD
Authoring date:
2020-09-06

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Meta Information


ICD:[  ]
Category:
Neurologic
MedDra ID:[  ]
MedDra Level:[  ]

Notes


- The gastrointestinal tract is the major site for L-dopa decarboxylation, and this metabolism is problematic because dopamine generated in the periphery cannot cross the blood-brain barrier and causes unwanted side effects. Thus, L-dopa is coadministered with drugs that block peripheral metabolism, including the AADC inhibitor carbidopa. Even with these drugs, up to 56% of L-dopa fails to reach the brain. Moreover, the efficacy and side effects of L-dopa treatment are extremely heterogeneous across Parkinson’s patients, and this variability cannot be completely explained by differences in host metabolism. (2)

- Parkinson's disease is not one, but two diseases. The study showed that some patients had damage to the brain's 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 brain's dopamine system was visible (3)

- Faecalibacterium and Ruminococcus were most consistently reduced in PD compared to controls. (4)

- The most common bacteria found in the stool samples included Bacteroides, followed by Faecalibacerium, Gemmiger, Roseburia, Prevotella, and Ruminococcus. Constipation severity and age were positively associated with the alpha-diversity or abundance of a genus in the gut. (5)
- The lowest physical activity and severe constipation were associated with Firmicutes enterotype, but high physical activity was associated with Bacteroides. (5)

- severe constipation was associated with a decreased abundance of Faecalibacterium. (5)

- 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. (6)

- The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. (8)

- Increase of D-Laktat und Glykolat has amelorative effects on Parkinson disease.
- D-Laktat is produced by lactobacillus bulgaricus (?)

Shared Notes


  • [1.1
    - 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.
  • [1.2
    - The gastrointestinal tract is the major site for L-dopa decarboxylation, and this metabolism is problematic because dopamine generated in the periphery cannot cross the blood-brain barrier and causes unwanted side effects. Thus, L-dopa is coadministered with drugs that block peripheral metabolism, including the AADC inhibitor carbidopa. Even with these drugs, up to 56% of L-dopa fails to reach the brain. Moreover, the efficacy and side effects of L-dopa treatment are extremely heterogeneous across Parkinson’s patients, and this variability cannot be completely explained by differences in host metabolism.
  • [1.3
    - The most common bacteria found in the stool samples included Bacteroides, followed by Faecalibacerium, Gemmiger, Roseburia, Prevotella, and Ruminococcus. Constipation severity and age were positively associated with the alpha-diversity or abundance of a genus in the gut. (5)
    - The lowest physical activity and severe constipation were associated with Firmicutes enterotype, but high physical activity was associated with Bacteroides.
    - Severe constipation was associated with a decreased abundance of Faecalibacterium.
  • [1.4
    - These bacteria consume dopamine, producing meta-tyramine as a by-product. The meta-tyramine by-product may contribute to some of the noxious L-dopa side effects.
    - Enterococcus faecalis (E. faecalis), ate all the L-dopa, every time. With this discovery, the team provided the first strong evidence connecting E. faecalis and the bacteria enzyme (PLP-dependent tyrosine decarboxylase or TyrDC) to L-dopa metabolism.
    And yet, a human enzyme can and does convert L-dopa to dopamine in the gut, the same reaction carbidopa is designed to stop. Then why, the team wondered, does the E. faecalis enzyme escape carbidopa reach?
    Even though the human and bacterial enzymes perform the exact same chemical reaction, the bacterial one looks just a little different. Maini Rekdal speculated that 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.
  • [1.5
    - The relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients.
    - Severe patients exhibited elevated levels of Verrucomicrobiae than controls, and a significant difference was evident when compared to the mild PD group.
    - Consequently, although both PD groups exhibited reduced commensal bacterial action, when coupled with high levels of Verrucomicrobiae in the severe PD group this 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.

Common References