Parkison’s and the Gut: An Update

I haven’t given you a Parkinson’s-and-the-biome update in several months now, and as yesterday I read a great review of the current status of our knowledge on the connection between the two, I figured it was time.[i]

I am sure that most of you are very familiar with Parkinson’s Disease (PD), which is the 2^nd most common neurodegenerative disorder after Alzheimer’s.  We have known for several years now, that it appears that the disease starts in the gut, although the exact mechanism of action is still unknown.  It seems, reading this paper, that the generally accepted (simplified) scenario right now is the following:

An unknown pathogen damages the nerves of the GI tract, resulting in the mis-folding (distortion) of a protein called α-synuclein (also known as Lewy bodies or Lewy neurites).  These Lewy bodies first accumulate in the gut.  Through various mechanisms, including the vagus nerve (which connects the brain to the gut’s nervous system), they move into the brain, including the substantia nigra, destroying the dopamine-producing cells there, resulting in the symptoms of the disease.

There is a large body of research now supporting this model:

1. Lewy bodies have been found in the intestinal wall, including in the earliest stages of the disease. When serious research into PD started, about 40 years ago, these were “…quickly recognize in the GI tract of PD subjects as a clinical implication and pathological hallmark of PD.”  The presence of α-synuclein pathology, in fact, allows the progression of PD to be divided into stages. Early on, the patients display gastrointestinal symptoms like constipation, insomnia, the impairment of the sense of smell, with α-synuclein pathology evident in the olfactory bulb and the vagus nerve.  In the next stages, movement-related symptoms appear, such as tremor, rigidity, and postural instability (balance issues), and the substantia nigra may be positive for α-synuclein.  In the last stages, the patient will have severe motor issues, as well as potentially neuropsychiatric disturbances, and the Lewy bodies will reach other parts of the brain, like the cerebral cortex.
2. α-synuclein is a normal protein in humans, but its exact purpose is unknown. I have read in other papers that it is thought to be a part of the immune system. In this paper, they suggest that it  “…plays a role in modulating the supply and release of dopamine to regulate neurotransmission.”  In PD, a folded (distorted) form of the protein accumulates in different parts of neurons.
3. The “unknown pathogen” well, yeah – it’s unknown right now. Its effects though can be seen in damage to the nervous system of the gut, which is also thought to be the cause of the GI symptoms seen early on in PD.  80% or more of PD patients have gastrointestinal symptoms related to the disease.  By the way, the pesticide, rotenone, when given to animals orally, can “…induce PD-like neuropathological changes…”  So environmental causes are most certainly a possibility.  In fact, as I was reading the paper, I remembered reading this little article a couple of years ago, on research looking into the pesticides/PD connection. You can also read more about the relationship of diseases, including PD, to other toxins in the environment here.
4. We know that severing the connection of the vagus nerve to the brain protects against the development of PD, which adds to the accumulating evidence of the gut being the origin.
5. This paper briefly describes other fascinating research which, in different ways, shows the same: the gut origin of the disease.  For example,  researchers found that 62 patients with PD “…displayed α-synuclein accumulation in gastric, duodenal, and colonic biopsies more than 8 years prior to the onset of the motor symptoms of PD.”  Holy cow, right?
6. The vagus nerve pathway is not the only one that is suspect: leaky gut has been found to be a major factor in those with PD as well, which allows toxins from the gut easy access to the blood stream and brain.  Researchers have found inflammation in the central nervous system in those with PD, associated with altered gut bacteria:  all these factors demonstrate that the gut microbiome “…is associated with and involved in gut permeability and the inflammatory response in PD patients…these findings are consistent with observations that the GM may be directly or indirectly involved in gut permeability and inflammatory responses in the GI and CNS  in PD and hence may affect PD pathology.”  (I’ve written about leaky gut and PD here.)
7. Currently, a growing body of research shows that these “gut-initiated pathological processes” are the result of disturbances of the gut bacteria. (This does not, of course, preclude pesticides, which absolutely can affect the gut bacteria.)  The article lists many changes in specific species of gut bacteria. For the sake of brevity,  I will mention only a few especially interesting ones.  Those with PD have been found to have low levels of Prevotellaceae, which produces beneficial short-chain fatty acids as well as thiamine and folate, all of which are found at low levels in those with PD.  As I have mentioned before on this blog, Prevotella is known to improve gut barrier integrity.  And one more example for you:  levels of Enterobacteriacceae is positively correlated with the severity of postural instability  and gait difficulty found  in those with PD.
8. Interventions to improve the quality of the gut bacteria (prebiotics, probiotics, diet, exercise, stress reduction, etc.) are “…supported by the fact that enzymes involved in dopamine synthesis in the brain are controlled by the GM [gut microbiome] and the GMBA [gut microbiota-brain axis].” Species like Bacillus are actually dopamine producers, believe it or not.  I wrote about the status of the research on this back last November, here.  We’re not there yet, but as you know I always say, if it can’t hurt and it could help, do it.
9. Conclusion: “PD pathogenesis may be caused or exacerbated by GM disorder and microbiota-induced inflammatory responses.”  We don’t know for sure, but the weight of evidence suggests (more so every day) that PD is initially a gut-microbiome disorder.

If this subject particularly interests you, as it does me (seeing as I have multiple friends who have developed the damn disease in their 40s and 50s – INSANE), take some time to check out some of my other posts on the subject.   There are a lot!

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[i] Yang, D, et. al. The role of the gut microbiota in the pathogenesis of Parkinson’s Disease. Frontiers in Neurology. 2019.  DOI: 10.3389/fneur.2019.01155.