The Gut Health Connection In Parkinson’s disease

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In this blog entitled ‘The Gut Health Connection And Parkinson’s disease’ I am going to discuss the connection between the gut microbiome and neurodegenative disease, in particular, Parkinson’s..

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

The Gut Health Connection And Parkinson’s disease

Changes in the gut microbiome may cause alterations in the integrity of the gut lining, contributing to excess intestinal permeability, (ie leaky gut). This may affect not only gut epithelial cells (cells that line the gut) and immune system, but also the enteric nervous system  including both neurons and glial cells (a type of nerve cell).

The bidirectional brain-gut-microbiome axis interactions modulate pro- and anti-inflammatory responses. It has been suggested that the changes in the gut microbiome associated with intestinal inflammation may contribute to the initiation of α-syn misfolding (1)..

There is a growing number of evidence confirming that these changes in the gut microbiome precede or during the course of Parkinson’s disease.

The Blood-Brain Barrier And Parkinson’s disease

In a germ-free animal model, it has been found that the gut microbiome influences the blood-brain barrier permeability (aka leaky brain) associated with reduced expression of the tight junction proteins in a similar way as it affects the gut lining. (1)

SIBO And Parkinson’s Disease

Recent studies reported high prevalence of SIBO (small intestine bacterial overgrowth in Parkinson’s, ranging from 54% to 67%. (1)

Parkinson’s has been associated with gastroparesis and impaired gut motility which may predispose to SIBO.

In the study by Fasano et al, the presence of SIBO reported in 54% of PD subjects, was associated not only with the gut symptoms but also with motor symptoms. Interestingly, the researchers found that there was improvement in motor fluctuations following treatment with the antibiotic, rifaximin.

In another study SIBO was detected in 25% of PD patients and occurred early in the disease course. According to that report, SIBO was not associated with worse gut function, but independently predisposed to worse motor function.

How Would SIBO Cause Parkinson’s?

It is possible that SIBO contributes to motor dysfunction by disrupting small intestinal integrity leading to immune stimulation and/or alteration in L-dopa absorption. SIBO may cause changes in the gut permeability which promote translocation of bacteria and toxins across the gut lining, inducing the pro-inflammatory response (1).

Leaky Gut And Parkinson’s

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).

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.”

H. Pylori And Parkinson’s Disease

The potential role of Helicobacter pylori (HP) in Parkinson’s, both with regard to the pathogenesis of Parkinson’s itself and the development of motor symptoms fluctuation, remains controversial. (1)

Gastric ulcers, strongly related to HP infection, have been associated with Parkinson’s since 1960s. Based on the observation of an age-associated increase in the levels of antibodies against HP in Parkinson’s patients, researchers proposed that HP infection predisposes to autoimmunity that results in neuronal damage leading to eventual parkinsonism.

In fact, HP infection may increase the risk of PD. Nielsen et al showed that prescription of HP eradication drugs and proton pump inhibitors five or more years prior to the diagnosis of PD were associated with 45% and 23% increase in the PD risk, respectively. At the same time eradication of HP infection has been shown to ameliorate symptoms of PD.

Currently, HP eradication in PD patients treated with L-dopa is recommended as it may improve the bioavailability of the drug and reduce motor fluctuation (1).

Conclusion:

“Both clinical and neuropathological evidences indicate that neurodegenerative changes in Parkinson’s  are accompanied by gastrointestinal symptoms that may precede or follow the central nervous system impairment. Dysregulation of the brain-gut-microbiota axis may significantly contribute to the pathogenesis of Parkinson’s. The gut seems to play a critical role in the pathophysiology of Parkinson’s representing a route of entry for a putative environmental factor to initiate the pathological process”. (1)

“The close relationship between gut dysbiosis, intestinal permeability (leaky gut) and neurological dysfunction suggests that the gut microbiota modification may provide a promising therapeutic option in PD”. (1)

References

  1. Brain-gut-microbiota axis in Parkinson’s disease (click here)
  2. Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways (click here)
  3. Impaired tissue barriers as potential therapeutic targets for Parkinson’s disease and amyotrophic lateral sclerosis (click here)
  4. The Link between Gut Dysbiosis and Neuroinflammation in Parkinson’s Disease (click here)
  5. Intestinal Decontamination Therapy for Dyskinesia and Motor Fluctuations in Parkinson’s Disease (click here)
  6. Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation (click here)
  7. Leaky gut, dysbiosis, and enteric glia activation: the trilogy behind the intestinal origin of Parkinson’s disease (click here)
  8. Parkinson’s Disease and the Gut: Future Perspectives for Early Diagnosis (click here)
  9. The treatment of gastroparesis, constipation and small intestinal bacterial overgrowth syndrome in patients with Parkinson’s disease (click here)
  10. The gut-brain axis and Parkinson disease: clinical and pathogenetic relevance (click here)
  11. Beyond here be dragons: SIBO in Parkinson’s disease (click here)
  12. Small intestinal bacterial overgrowth in Parkinson’s disease (click here)
  13. Association of small intestinal bacterial overgrowth with Parkinson’s disease: a systematic review and meta-analysis (click here)
  14. Prevalence of small intestinal bacterial overgrowth in Chinese patients with Parkinson’s disease (click here)
  15. Gastrointestinal dysfunction in Parkinson’s disease (click here)
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