It began with a gut feeling. Or at least that is one of the theories about how Parkinson’s disease develops that researchers continue to investigate.
It seems that every week, another research study provides additional insight into the gut-brain connection, and the (increasingly likely) possibility that Parkinson’s disease begins in the gut.
What does this mean?
[Disclaimer: I’m neither a doctor nor a research scientist. This article should not be considered medical advice or nutrition advice. This is just one patient’s attempt to better understand what is affecting them. Please keep in mind that this is discussion of theories, not proven facts.]
Before we begin, it is important to note that PD itself is likely multiple different diseases with similar effects and progression within the brain.
The gut-brain theory is that Parkinson’s disease can begin when a (still unidentified) foreign agent enters the body via the gastrointestinal system, triggering an abnormal alphasynuclein/Lewy body response (probably an immune system response that is not yet understood), which then travels into the central nervous system (CNS) via the vagus nerve.
The so-called Braak hypothesis, which was first proposed in 2003, is the foundation upon which the PD gut-brain theories are based.
Heiko Braak is a German anatomist who specializes in neuroanatomy. In 2003, his team proposed a staging theory for the progression of Parkinson’s Disease, based on post-mortem study of 168 autopsied patients: 41 diagnosed with PD; 69 with no PD symptoms, but with Lewy bodies in their brains; and 58 with no PD and no evidence of Lewy bodies. This analysis allowed the team to develop a theory for how PD spreads within the body and brain.
Recommended further reading:
It is important to note that despite years of research, this area of research remains a theory. And there are theories inside of theories, attempting to understand how this overall process unfolds (or misfolds, in this particular scenario).
When we talk about the gut-brain connection, we often make reference to gut bacteria. Gut bacteria is not an infection or medical condition. We all have gut bacteria, which is a complex community of microorganisms that live in our digestive tracts. Modern science refers to this our microbiome. There are as many of these bacteria cells (if not more) in our body as there are our own human cells. Our body has a symbiotic relationship with these microorganisms.
The composition of each person’s microbiome varies so much that we are still trying to identify and understand their differences. For example, earlier this year, a February 2019 study just identified 2000 previously unknown species of gut bacteria.
One of the most obvious ways that gut bacteria can affect Parkinson’s is that there are actually some strains of bacteria that consume levodopa, limiting the amount of medication that can actually pass through the blood brain barrier to reach the brain, where it is needed to produce dopamine.
Two weeks ago, University of Montreal scientists released results from a study where mice infected with bacteria that cause mild intestinal infections exhibited Parkinson’s like symptoms later in life. The findings provide a model in which intestinal infections could act as a trigger for Parkinson’s disease.
This is interesting for several reasons, but what I find interesting is that the original gut infection may be long gone by the time any motor symptoms are encountered.
Last week, a research study found that spicy food lovers may be at greater risk of dementia than those who prefer more bland foods. A 15-year study revealed that those who ate more than 50 grams of chili a day had double the risk of cognitive decline as they aged. The memory decline was more significant in those who were slim. Dr. Zumin Shi from Qatar University, who led the study commented, “Chili consumption was found to be beneficial for body weight and blood pressure in our previous studies. However, in this study, we found adverse effects on cognition among older adults.”
Could chilis trigger mild adverse intestinal inflammation, with a possibility of eventually effecting the brain? That’s an intriguing possibility, but before jumping to that conclusion, more studies are needed to corroborate the link between spicy food and increased risk of dementia, as the authors of this study also point out that the chili lovers in this study had a lower income and socioeconomic factors may also be a consideration.
Three weeks ago, Johns Hopkins researchers released results from a mouse study that injected mouse alphasynuclein preformed fibrils into gastrointestinal muscles that were densely innervated by the vagus nerve, and demonstrated that under certain conditions, this would spread to the brain via the vagus nerve. Co-senior study author Ted Dawson, professor of neurology at the Johns Hopkins University School of Medicine commented, “When the initial experiments started to work, we were utterly amazed.Now it is fairly routine for our research team.”
This is interesting, because it shows that abnormal alphasynuclein protein folding that starts in the gut could spread to the brain via the vagus nerve…in a mouse, at least.
There are obviously major differences between the biology of a mouse and a human, so mouse studies are not always an accurate predictor of disease behavior in humans. But, interestingly enough, did you know that the effectiveness of levodopa in treating movement disorders was first discovered in an animal study using rabbits?
Levodopa is the cornerstone of PD treatment. It was legitimized by a landmark 1967 study which showed that patients with PD tolerated a very slow, gradual build-up of levodopa dosage and then began to achieve dramatic, revolutionary benefit as therapeutic doses were reached.
Why were they trying to use levodopa to treat PD in the first place? The first clinical trial result on humans was published in 1961. However, all of these trials were predated by studies on rats and rabbits, most notably Arvid Carlsson’s 1957 research that identified levodopa as having an effect in restoring impaired movement in rabbits. Carlsson was awarded a Nobel Prize much later, in 2000, in recognition of the significance of this discovery.
Back to the gut…
One of the most interesting research studies involving PD and gut bacteria, took a sample of human gut microbiota from people with PD, and implanted the sample into the gut of previously germ-free mice. Remarkably, this induced motor dysfunction in the mice!
Various research studies have attempted to identify commonalities in the gut bacteria composition of people with PD, contrasted with people who do not have PD. But, this remains difficult, because as mentioned earlier, researchers are still discovering previously unknown species of bacteria.
It sounds crazy, but research has shown that a specific type of gut bacteria, prevotella copri, has an involvement in the development of rheumatoid arthritis (RA), implying that RA is an immune system related disease.
The mouse study where they transferred gut bacteria from a person with PD to a mouse, and it caused motor dysfunction is intriguing. But could a similar approach, taking gut bacteria from a healthy subject and transplanting it into the gut of someone with an immune disease, cure or at least alleviate symptoms?
Mouse studies suggest there is a possibility that this could work:
This procedure is referred to as Fecal Microbiota Transplant (FMT). The idea behind FMT is that good bacteria in healthy stool samples is transferred to an unhealthy individual to repair whatever is going wrong in the gut.
And while this can be done similar to an enema process, more frequently it is done orally. In another article, we described how it is being done in a research study at the Kelsey Research Foundation UTHealth Center for Microbiome Research in Houston, Texas.
In a UTHealth lab, the stool samples are mixed with saline, filtered twice, freeze dried, then put in capsules. The basic transplant takes place in pill form.
As the pathogenesis of Parkinson’s Disease is still unknown, there are many questions as to whether this treatment would have any effect on PD. Most of the current FMT efforts are focused on treatment of C. diff, but research is investigating other immune diseases, including the possible effect on PD.
While we have already made clear that this article is neither medical nor nutrition advice, we would still recommend that you don’t try this at home.
In short, there is still a lot of research that needs to be done. But overall, gut health may play a more significant role in our overall health than many of us suspected in our younger years.
Probiotic and prebiotic foods and supplements may help tip the balance in the microbiome toward healthy bacteria.
Probiotics contain actual live healthy bacteria strains, and include certain fermented foods and beverages including kefir, kombucha, kimchi and traditional sauerkraut.
Prebiotics are foods that pass through the stomach to the intestines without being fully broken down, and that provide nutrients to stimulate the growth of good bacteria.
Are bad gut bacteria to blame for PD? If they are, once the PD process starts, is it too late to stop it in the gut? Unfortunately, there are no answers, only theories. Which means that if you’ve managed to read this far, there is no conclusion to this article.