Leaky Gut And Parkinson’s disease

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Welcome to my blog entitled ‘Leaky Gut And Parkinson’s disease”.

Before we start, other blogs that you might be interested in, include:

Increased gut permeability (leaky gut) and alterations in gut microbiota are now widely accepted as relevant to the etiology, course and treatment of many neuropsychiatric disorders, including Parkinson disease (PD). (1)

Leaky Gut And Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Despite its high frequency the etiology is still unclear; several lines of evidence show that an inflammatory process is implicated in the pathogenesis of this disorder; where activation of brain microglia plays a central role in the damage of dopaminergic neurons.

Although a wide array of data on the biological underpinnings of Parkinson’s has not yet been linked to such gut-associated changes, increased gut permeability and dysregulated microbiota alter many pathways germane to Parkinson’s. (1)

Evidence also implicates an altered gut microbiome (dysbiosis) through the systemic release of endotoxins such as lipopolysaccharide and other metabolic products. This exposure may be enhanced by increased permeability of the intestinal (“leaky gut”) and the blood brain barrier; enhancing the entrance of microbiome-produced substances into the central nervous system.

How Might Leaky Gut Contribute To Parkinsons’ disease?

Some of the known mechanisms which connect leaky gut and Parkinson’s include (1):

  • Increased oxidative and nitrosative stress.
  • Immune-inflammatory processes.
  • Tryptophan catabolites.
  • Alterations in serotonin and melatonin pathways.

In this paper the authors conclude:

“By driving tryptophan down the kynurenine pathway, pro-inflammatory cytokines and chronic stress-driven activation of the hypothalamic-pituitary-adrenal axis decrease the availability of serotonin as a precursor for activation of the melatonergic pathways. Decreased local melatonin synthesis in glia, gut, neuronal and immune cells is likely to be important to the etiology, course and management of PD.”

Leaky Gut, SIBO, And Parkinson’s disease

Parkinson’s disease is neurodegenerative disorder with an initial robust response to levodopa. As the disease progresses, patients frequently develop dyskinesia and motor fluctuations, which are sometimes resistant to pharmacological therapy.

In one study (4) among 84 consecutive patients with Parkinson’s, the authors selected 14 with levodopa-induced dyskinesia and motor fluctuations with a Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part IV ≥ 8 points following a trial of pharmacological adjustment 2-3 months prior to study enrollment or adjustments in deep brain stimulation therapy.

Patients received treatment with sodium phosphate enema followed by oral rifaximin (an antibiotic) and polyethylene glycol for 7 and 10 days, respectively.

Evaluations between 14 to 21 days after starting treatment showed improvement in MDS-UPDRS-IV; duration of medication “Off”-state ; functional impact of motor fluctuations and complexity of motor fluctuations.

Marked to moderate improvement in dyskinesia was observed in 57% of cases with blinded evaluation of videos. About 80% of patients perceived moderate to robust improvement at follow-up (4).

A therapeutic strategy aimed at decontamination of intestines showed benefit in motor fluctuations and dyskinesia. (4)

Conclusions: Leaky Gut And Parkinson’s disease

The intestinal barrier show signs of disruption in patients with idiopathic Parkinson’s disease. A substantial body of evidence shows that defects in the gut lining, both in the gut and within the cerebral vasculature, can result in increased vulnerability of tissues to external factors potentially participating in the pathogenesis of Parkinson’s.

As such, restoration of tissue barriers may prove to be a novel therapeutic target in neurodegenerative disease.

It seems clear that there is a connection between imbalances in the gut microbiome, leaky gut, and Parkinson’s disease. More research is required to unpack this complex connection.

References

  1. Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways (click here)
  2. Impaired tissue barriers as potential therapeutic targets for Parkinson’s disease and amyotrophic lateral sclerosis (click here)
  3. The Link between Gut Dysbiosis and Neuroinflammation in Parkinson’s Disease (click here)
  4. Intestinal Decontamination Therapy for Dyskinesia and Motor Fluctuations in Parkinson’s Disease (click here)
  5. Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation (click here)
  6. Leaky gut, dysbiosis, and enteric glia activation: the trilogy behind the intestinal origin of Parkinson’s disease (click here)
  7. Parkinson’s Disease and the Gut: Future Perspectives for Early Diagnosis (click here)
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