PdCure.org

  Providing resources and ideas for therapies and medical developments for Parkinson's disease:

 

Probiotics and Parkinson's Disease:

The human intestinal tract is home to about 100 trillion bacteria (about 3 lbs) known as the microbiome. This gut microbiome plays a key role in developing and regulating our immune system. The interactions between the gut and surrounding nerves is being studied as it may be a pathway to the brain and affect the central nervous system. Both the presence and absence of bacteria have been found to be topics of interest for Parkinson's researchers. Lower levels of some gut bacteria may lower the protection from some environmental toxins and produce compounds that help fight inflammation. Studies are on-going to determine the levels of bacterial and chemical compound concentrations and their correlations to numerous disease states including Parkinson's. The bacteria which make up the microbiome are also essential for breaking down our food, generating endocrine/hormone activators, generating neurochemicals and teaching our immune system to recognize invading pathogens. The gut is also the general entry point for exposure to pesticides and herbicides and also impacts medication absorption. Our gut microbiome is affected by diet (anything we consume), pharmaceuticals, stress, environment and exercise. Constipation is also reported as one of the earliest Parkinson's disease symptoms and related to gut health. Probiotics have a direct effect upon the gut microbiome and has become a field of study for Parkinson's researchers.

References:

 

Human intestines

 

While we have not found any research on effective human trials of probiotics and Parkinson's Disease, there has been some advancements made in the lab with transgenic worms. Transgenic Caenorhabditis elegans worms have had their DNA altered to have portions of their DNA resemble human DNA. Scientists at the University of Edinburgh use transgenic experimental subjects to more closely represent a human response to drug treatment. The results of the study show that the probiotic bacterium Bacillus subtilis PXN21 inhibits, delays, and reverses alpha-synuclein aggregation. Alpha-synuclein is the protein that when mis-folded, has neurotoxic properties which kills neurons, causing Parkinson's disease. This bacteria produces chemicals that change how enzymes in cells process specific fats called sphingolipids. This probiotic is available commercially from Amazon, Walmart or directly from the manufacturer.

See reference article Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans or a brief layman's overview Gut bacteria could guard against Parkinson's

A study by the University of Alabama released in 2017 showed that individuals with Parkinson's often had a gut microbiome that was different and was either affecting pesticides and chemicals ingested, differently or being affected differently by chemicals and pesticides. This is particularly relevant since exposure to herbicides and pesticides are known to increase the risk of developing Parkinson's. They also found that the uptake of Parkinson's medications, and thus their effectivity, was influenced by one's microbiome.

Reference:

Probiotics

Gut Biome-Parkinson's Differences:

Research has shown that the gut microbiome of Parkinson's patients is in a state of dysbiosis or out of balance with the following gastrointestinal differences:
  • elevated levels of Indican bacteria which affects the intestinal barrier integrity and permeability. High levels of Indican are an indicator of gut dysbiosis (microbiome out of balance).
    Increased urinary indoxyl sulfate (indican): new insights into gut dysbiosis in Parkinson's disease (2015)
    "In patients suffering from PD indican urinary concentrationswere significantly higher than in healthy controls (approximatelytwice as high)"
    "Pathogenic gut microbiota likely induce barrier dysfunction, promoting inflammation and neuro-inflammation due to increased lipopolysaccharide and pro-inflammatory cytokines"
    "PD is higher amongst subjects who consume high quantities of dairy products, which are an important source of tryptophan. Indeed, we found that such products are associated with higher urinary indican concentrations"
    DOI: 10.1016/j.parkreldis.2015.02.004
  • significant decrease in Prevotellaceae bacteria which produces mucin which protects the gut lining
  • reduced levels of short-chained fatty acids which is directly associated with increased gut inflammation and constipation (ref Koh et al. 2016)
  • significantly elevated Enterobacteriaceae bacteria which has been associated with postural instability and gait difficulty.
    Gut microbiota are related to Parkinson's disease and clinical phenotype (Scheperjans et al 2015)
    "The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD"
    DOI: 10.1002/mds.26069
  • Increased alpha-synuclein aggregation in colon biobsies (a sign of inflammation).
    It is also believed that the spread of alpha-synuclein pathology may occur by travelling along the Enteric Nervous System and Vagus nerve from the gut to the brain.
    Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans (Goya et al 2020)
  • decrease in butyrate-producing bacteria
Parkinson's related gut-microbiome Research:

Current Clinical Trials:

Vagus Nerve:

The vagus nerve connects the brain to the heart, lungs and the gastrointestinal tract and is a bidirectional pathway. It also governs parasympathetic activity and modulates stress and calms inflammation to optimize digestion. While the brain and spinal neurons are part of the "central nervous system" (CNS), the vagus nerve is part of the "enteric nervous system" (ENS). The vagus nerve can be stimulated by deep breaths, stretching (reach your hands upwards), yoga, singing, huming, gargling, etc. It has been found that the microbiome composition in various areas of the gastrointestinal tract have an efffect upon brain neurochemistry. It is hypothesized that mis-folded alpha-synuclein proteins form deposits in neurons of the enteric nervous system leading to its neurodegeneration, characterized by intestinal permeability, oxidative stress and local inflammation ultimately resulting in constipation. The alpha-synuclein induced neurodegeneration eventually migrates to the central nervous system and motor control regions of the brain resulting in the pathology of Parkinson's disease.

Parkinson's Is Two Diseases:

Research out of Aarhus University in Denmark points to Parkinson's as two separate diseases:
  1. Brain-first Parkinson's
  2. Body-first Parkinson's

Brain-first Parkinson's: this variety of Parkinson's begins with the aggregation of alpha-synuclein in neurons of the brain and migrates to the peripheral autonomic nervous system. This variety of the disease is first characterized by tremors, gait disruption and freezing.

Body-first Parkinson's: this variety of Parkinson's begins in the peripheral autonomic nervous system (most likely the gut) and then travels to the brain via the vagus nerve. This variety of the disease is characterized by REM sleep behavior disorder and constipation (measured by colon volume and transit times) as the first signs of the disease pathology.

See Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study (2020)
DOI: 10.1093/brain/awaa238

Vagus nerve

Vagus nerve connects the brain, GI tract, heart, lungs, ...


Pros:
  • No negative side effects

Cons:
  • Not likely to effect anything beyond the blood-brain barrier to counter alpha-synuclein proteins in the substantia nigra. No data available on human efficacy.