Parkinson’s originates in the gut
Written by: Precision Staff
Parkinson’s Disease is very complex, and we are far from understanding all of its complexities or its ultimate causes. What we do know is that the gut is intrinsically involved and that monitoring possible gut dysbiosis seems to make a difference in predicting and possibly preventing Parkinson’s Disease. The evidence for the gut origin hypothesis for Parkinson’s also seems compelling.
Parkinson’s Originates in the GutParkinson’s Disease has long been known as a disease primarily affecting the brain and the rest of the central nervous system. While it is clearly true that Parkinson’s Disease is a progressive neurological disorder that causes tremors, affects mobility, can cause speech and bodily freezing episodes, affects balance, and eventually causes dementia, severe dysphagia, possible psychosis, and is a terminal illness. The median survival rate after initial diagnosis is nine years. The disease can often progress rapidly and essentially involves deep disturbances to the brain that affect both autonomic and cerebral functions. These symptoms and the onset of neurological decline cause many people (including many practitioners) to see the disease as neurological in origin, with any other symptoms as being secondary to neurological damage. This includes damage to the gut and gut symptoms like constipation, IBD, and general inflammation. This may be backward. There is compelling evidence that it’s not the neurological damage that has led to inflammation in the gut but rather that inflammation in the gut precedes the neurological damage in the brain.
We have long known that there is a gut-brain axis and that the gut can influence the brain and vice versa. We’ve written many times over the years about the gut-brain connection and how the microbiome specifically influences not only the gut's physical health but also the brain's physical health. Food allergies, a lack of fiber in the diet, and courses of antibiotics, among other things can trigger inflammation in the gut. Each of these things can cause a leaky gut- a loosening of the tight cellular junctions in the intestinal wall- that can permit inflammatory markers to spread in the bloodstream, causing inflammation elsewhere in the body. In addition to this mechanism for bodywide inflammation, the gut communicates directly with the brain through the vagus nerve. Inflammation in the gut, and even changes in the microbiome's composition, can trigger or suppress specific chemicals in the brain. This pathway of inflammation to the brain has been fairly well researched, and studies show how changes in the microbiome can influence things like depression through the effect that gut inflammation can have on serotonin and other brain chemicals. So, since we know there is a gut-brain axis, what does that have to do with Parkinson’s Disease specifically?
Even back in 1817, when physician James Parkinson first published his description of the disease in “An Essay on the Shaking Palsy,” he noted that as the disease progressed, “The bowels, which had been all along torpid, now, in most cases, demand stimulating medicines of very considerable power.” In this description, Parkinson is referring to constipation, which even today is recognized as a risk factor for Parkinson’s Disease, affecting two-thirds of all of those who have the disease. It’s, of course, possible that constipation is merely a symptom of the deterioration of the autonomic nervous system, and while this is undoubtedly somewhat true, remember that constipation is a risk factor, not merely a symptom. It’s also notable that Parkinson specified that the patients' bowels had been “all along torpid,” suggesting that it was either an early symptom or even preceded the neurological symptoms. This is all fairly general and only slightly persuasive. Let’s look more closely at the progression of Parkinson’s Disease to illustrate a more persuasive argument.
The fundamental cause of Parkinson’s disease is unknown, but a cluster of risk factors has been identified, as well as a pathway for the disease’s progression. It’s now largely agreed that a fundamental feature of the intermediate cause and progression of Parkinson’s Disease is the presence of α-Synuclein in the brain. α-Synuclein is a misfolded protein that “may exert deleterious effects on neighboring cells, including seeding of aggregation, thus possibly contributing to disease propagation.” (Leonidas Stefanis, 2011). This means that these folded proteins are likely the (or a) pathway for spreading the disease in the body. The argument that Parkinson’s Disease begins in the gut is hotly disputed. Those who argue that it begins in the brain are known as the proponents of the “brain-first” hypothesis of Parkinson’s Disease propagation, while the other side is known as the “gut-first” proponents. The gut-first hypothesis was first proposed by German researcher Heiko Braak. His hypothesis was based on the results of numerous autopsies he conducted looking for the presence of α-Synuclein. The results of his examination were that:
Braak noted that not only did these demonstrate that this meant that it was likely that α-Synuclein was the mechanism whereby the disease progressed, but that it seemed to begin in the brain stem and not elsewhere in the brain. We’ve already noted that the gut is connected to the brainstem via the vagus nerve. Braak’s next step was to look for α-Synuclein in the stomach walls. He found it. All of the patients whom he autopsied that had Parkinson’s Disease had α-Synuclein in the gut- and none of the controls did. Since then, many others have repeated his autopsy experiment with the same results. Almost all autopsies of Parkinson’s Disease patients had α-Synuclein in their guts, and none of the controls did. So we likely know that α-Synuclein is not found in the gut of non-Parkinson’s patients but is found in most of those who succumbed to the disease. This certainly leaves open the door for some other etiologies for Parkinson’s Disease, but in the vast majority of cases, it originates in the walls of the gut.
Braak found α-Synuclein in the stomach walls of his autopsies. What about the rest of the gut? How does this interact with inflammation in the gut? Another study, in 2016, determined that α-Synuclein could be found in the gut of future Parkinson’s Disease patients up to 20 years before their diagnosis of Parkinson’s- but not in the controls. This not only means that the rest of the gut is implicated but that screening for Parkinson’s might one day become a reality- especially since what treatment there is for the disease has the best response rates in very early Parkinson’s. What’s more, it appears that more recent research does indicate that gut dysbiosis (particularly inflammation) does precede the development of Parkinson’s Disease in the brain:
An additional piece of evidence for the gut-brain hypothesis is that undergoing a truncal vagotomy (where part or all of the vagus nerve is removed) results in a decreased risk of Parkinson’s Disease. Remember that the vagus nerve is the primary communication link between the gut and the brain. It’s important to note that the study only found success with this approach when performed 5 years or more before the onset of neurological symptoms of Parkinson’s Disease. Not only does this strongly suggest support for the gut-brain linkage in Parkinson’s Disease, but it also suggests that extremely early manifestation of α-Synuclein in the brain may still be too late to interrupt the progression of Parkinson’s Disease. The intervention must likely come when α-Synuclein is confined to the gut.
This brings us to the role of current testing and what can be done for early detection of Parkinson’s Disease. It may very well be that Parkinson’s Disease not only begins in the gut but is actually a disease of the gut. It’s entirely possible (and probably likely) that Parkinson’s Disease is a progression of gut-based IBD. A recent meta-study concluded:
IBD has been linked to an imbalance of gut microbes in the microbiome as well as food allergies and sensitivities. In addition to that, an imbalance in gut microbes has been demonstrated to have a possible impact on Parkinson’s Disease development:
So what does all this mean for Parkinson’s prediction and surveillance through testing? A real test for α-Synuclein in the gut that can be applied to the general population is somewhere in the future. In the meantime, there are a number of gut conditions that can be predictors/risk factors for Parkinson’s Disease: “Gastroparesis, dysphagia, irritable bowel syndrome (IBS) without diarrhea and constipation showed specific associations with PD” (Konings et al., Gut 2023;72:2103-2111). We have written extensively about the role of food allergies and sensitivities in gut inflammation, microbiome disturbance, and IBS. For now, the best surveillance for possible future Parkinson’s Disease for a patient is fourfold:
Examine the patient for symptoms of any of the four conditions noted above.
Surveillance of general gut conditions through a comprehensive gut test, such as this one offered by Precision Point Diagnostics: GI-MAP™ (Stool)
Testing for the state of intestinal permeability with the Precision Point Diagnostics Advanced Intestinal Barrier Assessment
Consider testing for food allergies and sensitivities, both of which are known to promote gut inflammation and intestinal permeability, with the Precision Point Diagnostics P88 Dietary Antigen Test
Parkinson’s Disease is very complex, and we are far from understanding all of its complexities or its ultimate causes. We know that the gut is intrinsically involved and that monitoring possible gut dysbiosis seems to make a difference in predicting and possibly preventing Parkinson’s Disease. The evidence for the gut origin hypothesis for Parkinson’s also seems compelling.