Home to around a thousand microbial species, the gut’s role in nutrient and drug metabolism is pivotal for immune function. As trillions of bacteria that thrive in the gastrointestinal system aid in the metabolic activity, the gut microbiome can also be influential in therapeutic research for an array of diseases, including Parkinson’s. And of late, its potential is being recognized.
With a dynamic composition of microbes in the gut, it is core to understanding its ability of being a drug target, particularly in precision medicine – treatments tailored to individuals based on their genetics and lifestyle. Conditions like irritable bowel syndrome, diabetes, obesity, autoimmune diseases like rheumatoid arthritis, and even some kinds of cancer have been linked to the gut microbiome. Microbiotica, a collaboration between Cancer Research UK and Cambridge University Hospitals NHS Foundation Trust, evaluated the potential of gut bacteria-based co-therapies along with immune checkpoint inhibitor therapy, to enhance the immune response in patients with melanoma who don’t tend to respond well to immunotherapy.
Like for cancer, therapeutic research of the gut microbiome is ongoing for various diseases. And novel discoveries suggest that the gut microbiome could even transform medicine for neurodegenerative diseases like Parkinson’s disease (PD).
But how exactly is the gut microbiome associated with the functioning of the brain?
As microbes play a significant role in the robust functioning of the gut wall, when the gut is unhealthy, nutrients fail to get absorbed, while toxins are taken up by the gastrointestinal system. This brings about a profound inflammatory reaction, which then spreads to the rest of the body, including the brain, according to Dr. Raphael Kellman, Functional Medicine Physician at Kellman Wellness Center in the U.S..
“There is this tremendous communication between the gut, the microbiome and the brain. It’s called a bi-directional highway, meaning there’s communication from the microbiome to the brain, and then from the brain to the microbiome,” said Kellman.
Parkinson’s and a perturbed microflora
How the brain and the microbiome communicate is via neurotransmitters – messengers that carry chemical signals from the neurons to other cells in the body. Serotonin and dopamine are two such brain chemicals that control body movement and regulate digestive functions. Both are associated with emotional processing and mental health, and a lack of the latter, is accountable for many of the symptoms of Parkinson’s.
Much like the brain, the gut manufactures dopamine and serotonin, a means for the microbiota to liaise with the brain. Kellman regards the gut microbiome as an intricate software that can send messages all over the body, and one that “artificial intelligence will never be able to replicate.”
Another pathway for the transmission of signals is the immune system, where the microbiome sends messages to the immune system, following which the messages are relayed to the brain.
And in a healthy gut, the brain’s functioning is at its peak, where communication is vigorous and memory remains unaffected. “There’s no brain fog, your ability, your motivation is powerful. Your ability to think in an optimal way is perfect, executive function is excellent, your mood is good,” said Kellman.
However, when the gut microflora is disturbed, problems arise. A disparity in the release of neurotransmitters is observed, and alarm signals are transmitted, causing the brain to be in a stressed state. Meanwhile, the immune system can also convey similar messages, leading to it becoming overactive, and thereby inducing inflammation.
“When there’s too much of an activation of the immune system, it could start damaging neurons to a point where over time, it can lead to degeneration of different neurons in different parts of the brain. Now this degeneration, eventually, it manifests as various neurodegenerative diseases like Parkinson’s disease, dementia, Alzheimer’s, and also just poor cognitive function. But it absolutely sets the stage for Parkinson’s disease,” said Kellman.
As the microbiome deteriorates, the immune system declines further, hence following a vicious cycle. Kellman said: “You can look at it as an ecosystem. An outer ecosystem is supposed to look luscious, and you could see it flourishing with all different shades of green. Now what’s happening in an outside unhealthy ecosystem… it’s starting to fade, and you’re starting to see colors, variations of brown. It’s a good metaphor for what’s happening in the inner ecology, the microbiome.”
This unfavorable gut environment foreshadows Parkinson’s, which is often characterized by tremors, stiffness, difficulty with balance and coordination, and sometimes accompanied by cognitive impairment. As more than 10 million people live with Parkinson’s disease, there is a need to expedite research in gut-microbiome-based therapies – a target that has only recently been discovered – despite most treatments focusing on receptors in the brain.
The gut microbiome: a drug target for Parkinson’s?
A study conducted by the University of Alabama in the U.S., revealed that there was an imbalance in the Parkinson’s disease gut microbiome. 30% of the gut bacteria differs in people with Parkinson’s when compared to those without the disease, proving a link between the two. There was an overabundance of pathogens, some indicative of inflammation. Bacteria like Bifidobacterium dentium, Actinomyces oris and Streptococcus mutans were elevated by more than six-fold, while Roseburia intestinalis and Blautia wexlerae had declined distinctly.
This relationship between the intestinal flora and Parkinson’s disease establishes the gut microbiome’s capability to act as a drug target to battle and even delay the progression of the disease.
According to Kellman, the gut microbiome, a root cause of neurodegeneration, is the ideal target for therapeutic research, and not the brain. He explained that a poor diet greatly contributes to the development and progression of Parkinson’s disease, and therefore, eating foods rich in fibers can transform gut microbiome health, and in turn, decelerates the aggravation of the disease.
A healthy gut, a healthy mind
Prebiotic foods – dietary fibers – like jicama, kiwi, spinach, artichokes and asparagus, among others, which are typically consumed to mitigate gastrointestinal issues, can improve the regulation of inflammatory processes. Eating fiber-rich superfoods raises the amount of short chain fatty acid (SCFA)-producing bacteria, which in the Parkinson’s disease gut, sees a notable loss of its kind. SCFAs, which are produced by microbes in the gut when these fibrous foods ferment, can modulate the levels of neurotransmitters, thus stalling Parkinson’s progression.
“It’s not so much what we’re eating, to say, what is the microbiome eating?” said Kellman, who believes that taking supplements as well as detoxifying the gut can reduce inflammation. He explained that the prolonged use of antibiotics, uptake of medicines like proton pump inhibitors and the excessive exposure to toxins, be it mold or pesticides, can adversely affect the microbiome.
Having treated people with Parkinson’s, Kellman recounts that patients see greater results when their gut microbiome is treated, rather than when they take the conventional route of medicine.
He said: “There’s not a patient that I’ve seen with Parkinson’s disease that has not improved, some so remarkably, that you can remove that medical history from their chart.”
“It’s a whole new reality that is happening behind firewalls that just people don’t know about. And that’s why it’s so important to disseminate this new information that, you know, it’s like two different worlds out there, one that doesn’t know any of this, and then another world that knows a whole new type of medicine that is rapidly evolving now.”
Apart from prebiotics, probiotics and psychobiotics are a sought-after avenue that could bear encouraging results with regard to Parkinson’s treatment. Probiotics are live microorganisms that restore the gut microbiota, and psychobiotics, whose potential is being investigated, have benefits like stimulating an antidepressant effect, an emerging intervention in mental health research. Probiotics like Bifidobacterium, Lactobacillus, and Streptococcus species, can alleviate the symptoms of bloating and abdominal stress in people with Parkinson’s disease, according to a study conducted in 2022.
Another mechanism by which the gastrointestinal flora could suppress inflammation is through fecal microbiota transplantation (FMT). FMT – stool transplant – is a technique by which the gut microbiota of a healthy donor is transplanted into a patient’s intestines, to reconstruct the flora in an unhealthy gut. Having proven its safety and efficacy for the treatment of gastrointestinal dysfunction, a study was conducted to understand its effectiveness in people with Parkinson’s. It was found that the quality of life, mental health and motor symptoms had improved in individuals at the three-month follow-up. However, whether the therapy can have a long-term beneficial effect is yet to be further explored for Parkinson’s.
Besides these therapies, recent studies have revealed how exosomes could address Parkinson’s symptoms. Exosomes – extracellular vesicles which regulate immune cells and gut microbes – mediate the transportation of α-synuclein in the brain. The misfolding of clusters of α-synucleins is a neuropathological hallmark of Parkinson’s disease. Yet to discover its full clinical potential, exosomes could act as biomarkers as well as vectors for Parkinson’s therapies.
Although not a cure, Kellman believes that focusing on the gut microbiome for Parkinson’s treatment is the right approach.
“I’m not the one saying this, science is saying this. This is the direction we must go, in order to see the best results. This is a new pathway to neurodegenerative diseases, by healing the gut, by healing the microbiome. This is the revolution.”
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