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Parkinson's Disease {40000200}

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Definition:
Parkinson's Disease
Class:[  ]

Details


Other Terms:
PD
Initialisation date:
2021-02-05

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Meta Information


ICD:[  ]
Category:
Neurology
MedDra ID:
10061536
MedDra Level:
pt

Notes


-A strain of Escherichia coli in the gut makes a protein called curli, which can prompt other proteins, including one called a-synuclein, to misfold. Some researchers suspect that these misfolded proteins transmit the error up the vagus nerve to the brain, where misfolded a-synuclei n is linked to disease symptoms.

- 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.

Shared Notes


  • [1.30
    - 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
  • [1.31
    - 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.
  • [1.32
    - Overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus.
  • [1.33
    - 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.
  • [1.19
    - 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.
  • [1.34
    - 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.
  • [1.35
    Toxic Bile acids produced by specifics Clostridium species may predispose to PD
  • [1.36
    - 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
  • [1.16
    - 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
  • [1.25
    - Increase of D-Laktat und Glykolat has amelorative effects on Parkinson disease.
    - D-Laktat is produced by lactobacillus bulgaricus.
  • [1.37
    - Higher number of bacterial mucin and host degradation enzymes link to PD.
    - The microbial contribute to the folate deficiency and hyperhomocysteinemia observed in patients with PD
  • [1.24
    - Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations
  • [1.38
    - In skin sebum of PD patients, metabolites belonging to ceramide, triacylglycerol, and fatty acyl classes were downregulated whereas glycosphingolipid and fatty acyl metabolites were upregulated.
  • [1.39
    - Trichloroethylene (TCE) is an environmental contaminant and Parkinson's risk factor.
    - Chronic TCE treatment in rats caused dopaminergic neurodegeneration.
    - TCE exposure elevated LRRK2 kinase activity in the nigrostriatal tract and causes dopaminergic pathology, endolysosomal dysfunction, protein accumulation.
  • [1.40
    - 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.
  • [1.50
    - 38 E. coli genes promote neurodegeneration.
    - Two of these genes, csgA and csgB, code for proteins that form curli, one type of bacterial amyloid fibers.
    - Curli cross-seeds and colocalizes with α-syn both in C. elegans neurons and human neuroblastoma cells.
    - Curli-induced α-syn aggregations down-regulate mitochondrial genes, causing energy failure in neurons.
    - Curli may have general effects in promoting neuropathologies induced by different aggregation-prone proteins, such as A-β in Alzheimer’s disease, Huntingtin in Huntington’s disease, and SOD1 in amyotrophic lateral sclerosis.
  • [1.51
    - Increased in PD: Lactobacillus, Bifidobacterium, Verrucomicrobiaceae and Akkermansia
    - Lower Abundance in PD: Faecalibacterium, Roseburia, Coprococcus, Blautia, Prevotella and Prevotellaceae
    - Fecal SCFA levels: reduced in PD patients
    - Butyrate synthesis: is reduced in Parkinson's disease
    - Harmful amino acid metabolites: increased in PD > worsening intestinal inflammation and constipation.
    - α-Synuclein-toxic forms penetrate initially the ENS > finally reach the CNS via the vagus nerve > trigger motor symptoms of PD.
    - Butyrate and propionate > neuroprotective effects > help restore motor skills in PD.
    - Gut Microbiota > convert food flavanols into phenolic acids
  • - B. Wadsworthia > large quantities in PD patients > increased sulfite production in the intestine.
    - Sulfite > neurotoxin > mediates the mitochondrial energy balance of the brain
  • - Decreased Lachnospiraceae > reduction in anti-inflammatory and neuroprotective metabolite in PD
    Increased Bacteroides and Verrucomicrobia > Metabolites correlated positively with the frequency of the proinflammatory cytokines TNF-α and IFN-γ
  • - Decreased Prevotella > faster PD progression
  • - Increased Enterobacteriaceae > Postural instability in PD patients.
  • - Gut Microbiota > produce polyphenol > protect against neurological diseases with α-syn toxicity
  • - Chronic constipation: one of the most important and widespread early symptoms of PD > affecting around 80% of patients and recognizing as signal decades before diagnosis.
  • - Bacterial overgrowth of the small intestine (SIBO): 25% of PD patients > inflammation-mediated effect.
    -SIBO > gastrointestinal dysfunction > increasing intestinal permeability, proinflammatory cytokine activation and, consequently, microglial activation > a deterioration in motor skills and can also affect the absorption of levodopa > PD
  • [1.29
    - Serotonin > protective factor of PD
  • [1.53
    - Aromatic (ar)-turmerone is a main component of turmeric oil extracted from Curcuma longa and has anti-inflammatory activity in cultured microglia.
    - ar-turmerone analogs > directly and potently protected dopaminergic neurons.
  • [1.54
    - There is a significant inverse relationship between the onset of Alzheimer's disease/Parkinson's disease (AD/PD) and cancer.
    - An increase in PIN1 expression is related to a delay in the onset age of sporadic AD, whereas a decrease in PIN1 expression is associated with a reduced risk of various cancers.
    - prostate, ovarian, and lung cancers show the greatest negative correlation with AD.
  • - PD patients, showing an increase in Akkermansia, Bifidobacterium, and Lactobacillus and a decrease in Prevotella
  • - The onset age of PD is directly proportional to the SCFA level, suggesting that SCFAs may have a protective effect on PD
  • - Tryptophan metabolites can cross the blood-brain barrier > activate AHR to regulate astrocytes and reduce central nervous system inflammation in AD and PD
  • [1.55
    The neuropathological hallmark of PD is the widespread appearance of alpha-synuclein aggregates in both the central and peripheral nervous systems, including the ENS.
    - Gut toxins can > induce the formation of α-syn aggregates in the ENS > transmitted in a prion-like manner to the CNS through the Vagus N.
  • [1.56
    - The relative abundance of Enterobacteriaceae is positively associated with the severity of postural instability and gait difficulty.
  • [1.57
    - 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.
  • [1.58
    - 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.
  • [1.59
    - 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.


[Coverage other Diseases (Overlap > 0.25)]

DiseaseOverlapCommon increased OrganismCommon decreased Organism
Parkinson's Disease 1.0000 140 (100%) : Acidaminococcus | Acinetobacter | Actinomycetales | Akkermansia | Akkermansia muciniphila | Alistipes | Alistipes ihumii | Alistipes obesi | Alistipes shahii | Alloiococcus | Anaerotruncus | Aquabacterium | Bacteroides | Barnesiella | Barnesiellaceae | Bifidobacteriaceae | Bifidobacterium | Bifidobacterium animalis | Bifidobacterium dentium | Bifidobacterium longum | Bilophila | Blautia | Brucella | Butyricicoccus | Butyricimonas | Candida albicans | Candida dubliniensis | Candidatus gastranaerophilales | Capnocytophaga canimorsus | Carnobacteriaceae | Catabacter | Catabacter hongkongensis | Cellulosimicrobium | Christensenella | Christensenella minuta | Christensenellaceae | Citrobacter | Citrobacter rodentium | Clavibacter michiganensis | Cloacibacterium | Clostridium cluster IV | Clostridium cluster XIVa | Clostridium cluster XVIII | Clostridium group XI | Clostridium spiroforme | Clostridium XIVb | Coprococcus | Coriobacteriaceae | Desulfovibrio | Dialister | Eggerthella lenta | Eisenbergiella | Enhydrob 91 (100%) : Actinomyces | Allisonella | Allobaculum | Bacillaceae | Bacillus megaterium | Bacteroidales | Bacteroides coprocola | Bacteroides dorei | Bacteroides fragilis | Bacteroides massiliensis | Bacteroides plebeius | Blautia | Blautia coccoides | Blautia glucerasea | Brevibacterium | Brevundimonas | Buchnera aphidicola | Bulleidia | Campylobacter ureolyticus | Candidatus Azobacteroides | Candidatus Azobacteroides pseudotrichonymphae | Capnocytophaga | Carnobacteriaceae | Clostridium | Clostridium leptum | Clostridium saccharolyticum | Collinsella | Coprococcus | Coprococcus eutactus | Corynebacterium | Desulfibrio piger | Desulfovibrionaceae | Dietzia | Dorea | Dorea longicatena | Eikenella | Epilithonimonas | Eubacterium biforme | Eubacterium hallii | Faecalibacterium | Faecalibacterium prausnitzii | Flavobacteriaceae | Gemella | Granulicatella | Haemophilus | Halobacillus mangrovi | Halomonas | Helicobacter pylori | Holdemanella | Hyphomonas | Kingella | Knoellia | Lachnospira | Lachnospiraceae | Lactobacillus |
Crohn's disease 0.2830 30 (21%) : Acidaminococcus | Acinetobacter | Anaerotruncus | Barnesiellaceae | Bifidobacterium | Blautia | Candida albicans | Citrobacter | Clostridium cluster XIVa | Coprococcus | Enterobacteriaceae | Enterococcus | Gardnerella vaginalis | Klebsiella | Lachnobacterium | Lachnospiraceae | Lactobacillus | Lactobacillus fermentum | Morganella | Odoribacter | Prevotella | Proteobacteria | Proteus | Ruminococcus | Ruminococcus torques | Shigella | Sphingomonas | Streptococcus | Streptococcus mutans | Veillonella 32 (35%) : Bacteroides fragilis | Bacteroides massiliensis | Blautia | Blautia coccoides | Clostridium | Clostridium leptum | Collinsella | Coprococcus | Coprococcus eutactus | Dorea | Eubacterium hallii | Faecalibacterium | Faecalibacterium prausnitzii | Gemella | Haemophilus | Holdemanella | Lachnospira | Lachnospiraceae | Lactobacillus | Limnobacter | Methanobrevibacter | Neisseria | Pasteurellaceae | Prevotella | Roseburia | Roseburia intestinalis | Ruminococcaceae | Ruminococcus | Ruminococcus callidus | Sphingobacterium | Stenotrophomonas | Streptococcus

Common References