In Conversation: Why Parkinson's research is zooming in on the gut
Parkinson’s disease affects millions of people around the world, but it remains unclear exactly what causes it, and there is currently no cure for this condition. In an effort to better understand the mechanisms involved, some researchers are now looking to the gut. Why, and what could this research reveal? In this installment of our In Conversation podcast, we discuss how gut health may play a role in Parkinson’s.
Share on PinterestDesign by Andrew Nguyen.Millions of people around the world live with Parkinson’s disease, a neurological condition that primarily affects mobility, balance, and muscle control, though its symptoms can include many other issues, from mood changes to gastrointestinal issues and a deterioration of memory and other cognitive functions.
According to data from the World Health Organization (WHO), the global prevalence of Parkinson’s has doubledTrusted Source in the past 25 years, and as per the most recent estimates, the disease has resulted in “5.8 million disability-adjusted life years” globally.
While much of this increase is driven by increasing numbers of older adults, there is also some evidence that age-adjusted incidence is also on the riseTrusted Source.
Dopaminergic medication, deep brain stimulation, and speech and occupational therapy are some of the treatments currently available to people with Parkinson’s disease, but researchers are constantly on the lookout for more and better treatments.
In order to pave the way to better treatments, scientists are first seeking to understand more about how Parkinson’s disease works, and what mechanisms in the body might affect its development.
Several studies from the past 12 months have focused on one particular aspect of Parkinson’s disease, namely gut health. But why is gut health important in Parkinson’s, and what could it reveal about the disease?
To find out more about the current research and how the disease can affect individuals, Medical News Today welcomed two guests to the latest installment of our In Conversation podcast: Dr. Ayse Demirkan and Gary Shaughnessy.
Dr. Demirkan is a senior lecturer in AI Multiomics for Health and Wellbeing at the University of Surrey in the United Kingdom, and co-author of a paper about the imprint of the microbiome in Parkinson’s disease, which appeared in Nature CommunicationsTrusted Source in November 2022.
Gary Shaughnessy is the chair of trustees at Parkinson’s UK, a research and support nongovernmental organization. In 2015, Shaughnessy received a diagnosis of Parkinson’s disease, and since then, he has been taking on regular physical challenges to raise money for Parkinson’s research.
Listen to this month’s podcast below, or on your preferred streaming platform:
Why look to the gut?
Over the past few years, an increasing amount of evidence has come to light indicating that there is a two-way communication route between the brain and the gut. Researchers have termed this the gut-brain axisTrusted Source.
The gut-brain axis has been implicated in many health conditions affecting the brain, from dementia to depression. And while the gut-brain connection may be less obvious in other conditions, it is, in fact, clearer in Parkinson’s disease, which, in some people, is also characterized by gastrointestinal symptomsTrusted Source, such as constipation.
One perspective on Parkinson’s disease, known as the Braak hypothesisTrusted Source, suggests that, in many cases, an unknown pathogen can reach the brain via two routes, one of which implicates the gut.
According to this hypothesis, one way for pathogens to reach the brain could be by being swallowed, reaching the gut, and then advancing to the brain via the vagus nerve — the longest cranial nerve that connects the brain with, among others, the intestines. This may then trigger the onset of Parkinson’s disease.
In our podcast, Dr. Demirkan acknowledged that, at first, the notion of looking to the gut to understand more about Parkinson’s disease might seem surprising, but that the Braak hypothesis provides an intriguing lens through which to assess potential mechanisms at play.
“[Through the Braak hypothesis,] there comes the idea that the disease actually starts in the intestines, and then through the vagus nerve, it spreads to the other tissues and toward the brain,” she explained.
According to her, Parkinson’s disease is the neurological condition most interesting to study in relation to gut health for one simple reason: Parkinson’s gut microbiome stands out the most.
Gut microbiome is different in Parkinson’s
Through the recent study they conducted, Dr. Demirkan and her colleagues saw that individuals with Parkinson’s disease had distinct gut microbiomes characterized by dysbiosis — the phenomenon of imbalance between so-called good versus bad bacteria.
Their study suggested that around 30% of the proportion of gut bacteria in people with Parkinson’s disease is different from those without Parkinson’s.
“We found one-third of these microbes [in the gut of people with Parkinson’s] to be different,” Dr. Demirkan said on the podcast.
“So this is a very strong indication of dysbiosis. And also how they [the bacteria] function, what kind of genes they carry, [these aspects were] also different. We found a reduced [amount of] short-chain fatty acid producers, for example, bacteria that [are] known to be gut-friendly […] We found increased pathogenic bacteria […], including Escherichia coli, and we found a lot of bacterial pathways disturbed as well, potentially affecting the well-being of the neuronal tissues.”
– Dr. Ayse Demirkan
Dr. Demirkan and her colleagues found that bacteria such as Bifidobacterium dentium — which can cause infections such as brain abscesses — were at significantly elevated levels in the gut of people with Parkinson’s disease.
Other infection-causing bacteria more abundant in people with Parkinson’s were E. coli, Klebsiella pneumoniae, which can cause pneumonia, and Klebsiella quasipneumoniae, which can cause similar infections.
The study conducted by Dr. Demirkan was not the only recent research to zoom in on the differences in gut bacteria.
Research from the University of Helsinki — published in May 2023 in Frontiers — in animal models of Parkinson’s disease, suggests that Desulfovibrio bacteria may be implicated in this condition. These bacteria produce hydrogen sulfide, which may lead to forms of inflammation.
Desulfovibrio also came up in a study from The Chinese University of Hong Kong, which appeared in May 2023 in Nature CommunicationsTrusted Source. This study, whose aim was to find a method of diagnosing Parkinson’s earlier, identified an “overabundance” of these bacteria in people with REM sleep behavior disorder and early markers of Parkinson’s.
REM sleep behavior disorder is a deep sleep disturbance tied to a higher risk of Parkinson’s disease. In people with this disorder, the usual brain mechanisms that prevent them from “acting out” the content of their dreams no longer work, which means that they perform uncontrolled movements in their sleep.
Shaughnessy told us that he, too, experiences deep sleep disturbances. “[O]ver the last few years, I have very really vivid dreams, and […] I’ve fallen out of bed a few times because I’m turning over doing something, you know, sort of dealing with whatever it is in the dream,” he described.
What are the potential mechanisms?
If gut bacteria do play a role in Parkinson’s disease, the question that arises is: What mechanisms might mediate their impact on neurological health?
One hypothesis hinted at in the studies on the link between the gut and the brain in Parkinson’s is that systemic inflammation may be one of the mechanisms involved, since some of the bacteria that are overabundant in this condition are pro-inflammatory, meaning that they can trigger inflammation.
There is research indicating that immunosuppressant medication is associated with a lower riskTrusted Source of Parkinson’s disease, which suggests that a similar type of medication may also help manage the condition.
Indeed, chronic brain inflammationTrusted Source is an important part of Parkinson’s disease, and some studies seem to indicate that systemic inflammationTrusted Source may worsen brain inflammation and thus contribute to disease progression.
Some inflammatory conditions have actually been linked with a higher risk of Parkinson’s. For example, one Danish study from 2018 suggested that people with inflammatory bowel disease (IBD) have a 22% higher risk of Parkinson’s disease than peers without this inflammatory condition.
In the podcast, Dr. Demirkan agreed that inflammation linked to Parkinson’s disease may start in the gut, caused by “bad” bacteria. However, she emphasized that this potential mechanism is not yet confirmed, and further research on this topic is necessary to draw firm conclusions.
Could diet fight dysbiosis in Parkinson’s?
If gut bacteria may play a role in Parkinson’s disease, it may seem reasonable to infer that diet could help fight gut dysbiosis and perhaps provide an easy option for symptom management.
While there are some dietary recommendations and nutritional supplements that may help provide some symptom relief for some people, it remains unclear just how much diet can actually do to alter the course of this disease.
One study from 2022 suggests that diets high in flavonoids — natural pigments found in many fruits — are linked to a lower risk of mortality in Parkinson’s disease.
And an older study, from 2018, argued that a protein found in many types of fish, called “parvalbumin,” may help prevent Parkinson’s disease by stopping alpha-synucleinTrusted Source from collecting into clumps in the brain — which is what happens in the brains of people with Parkinson’s, disrupting signals between brain cells.
However, when asked about the potential of diet and supplements to regulate gut bacteria in people with Parkinson’s, Dr. Demirkan expressed some reservations.
She emphasized that since people have different risk factors for Parkinson’s, as well as different iterations of the disease, it is difficult to make general recommendations that would actually prove helpful:
“It’s very difficult for me to advise anyone anything […] because we are all very individual, our gut microbiome is individual. So prevention [of the condition] is [one thing] I think, and the long-term maintenance is something else, together with the other complications of the disease. So I cannot really advise anything, but studies show there is a problem with increased sugar consumptionTrusted Source […] There are some intervention studies on diet indeed, but it’s very difficult [to conclude anything], as the studies are not really […] finalized. [It is difficult to know] how to advise an individual with a certain genetic and lifelong history of exposure to different things, because we don’t know what is in [them].”
Can exercise help with Parkinson’s?
There is, nevertheless, some research suggesting that exercise can be an effective means of managing the symptoms of Parkinson’s disease.
One study from 2022, published in Neurology, suggested that participating in regular, moderate-to-vigorous exercise could help slow down the progression of Parkinson’s disease for those in the early stages.
Research from 2017 advised that at least 2 and a half hours of exercise per week could help people with Parkinson’s improve their mobility while slowing down disease progression.
Dr. Demirkan agreed that exercise can be a helpful strategy for managing Parkinson’s disease. “[E]xercise itself is an amazing way of shaping our brain and body,” she said.
“[I]n terms of reversing [Parkinson’s] pathology, there are some large physiological effects that we can think about. If you’re running a marathon, for example, it’s a big thing that your body has to go through. […] [F]or instance, one thing is that your heat increase for a long time in like a […] feverish way, right? There is a long-term increase in the core heat, that’s one thing, and that should definitely have an important effect [on the gut],” she explained.
Indeed, some research suggests that the heat stress taking place during exercise could reduce intestinal blood flow, which eventually may impact the gut microbiome by potentially suppressing some bacteria and making room for others to expand.
As to which form of exercise is best for people with Parkinson’s disease, a Cochrane review published in January 2023 concluded that pretty much all forms of exercise can help improve life quality for those living with this condition.
According to the review authors, existing evidence suggests that aqua-based training “probably has a large beneficial effect” on quality of life. Endurance training is also helpful, both in improving life quality, in general, and in managing motor symptoms, in particular.
When it comes to managing motor symptoms, the authors write that dance, aqua-based exercise, gait/ balance/ functional exercise, and multi-domain training could all be equally helpful.
And some past research — in women with overweight but without Parkinson’s — has suggested that endurance training results in an increase in beneficial bacteria called Akkermansia, which contribute to improved metabolic function.
Shaughnessy, who regularly takes part in demanding and arduous marathons and other sports challenges to raise funds for Parkinson’s research told us that exercise has helped him more than anything in maintaining his well-being.
“[E]xercise has become a big part — was already a part of my life before [the diagnosis], but it’s become […] a big way of helping me to manage and control the condition,” he told us in the podcast.
“I gradually went from, you know, a bit of running to marathons. And then the latest thing I’ve done was a 14-day cycle from Liverpool to Ukraine — 1,400 miles, which was probably a little bit beyond my capability, to be honest,” he mused.
But challenging himself in this way, he said, truly helped him on a mental level. “[W]hile I’m exercising, I don’t feel like I have Parkinson’s, quite often,” Shaughnessy told us.
For him, it is all about focusing on what you are actually able to achieve at any given point in time, and aiming for that.
“[A big part] of managing the condition, I think, is around your mental attitude. Because when I first was diagnosed, I actually found it very difficult, running. And I’d go running as part of being on business trips abroad and so on, I’d run in cities I went to, and I did decline in the first months, quite rapidly in terms of my running. But my wife actually said to me, ‘just focus on what you can do, not what you can’t do.’ And that was a bit of a turning point for me. And, you know, by not worrying about [it], I’ve got to get better and go quicker, and just focus on enjoying my running. And, you know, actually, ironically, I have got better and I ran my personal best in the marathon in May this year — so, 8 years after diagnosis.”
– Gary Shaughnessy
====
