a promising target for Parkinson’s

Home to around a thousand microbial species, the gut’s role in nutrition and drug metabolism is critical to immune function. The trillions of bacteria that thrive in the digestive system aid metabolic activity, and the gut microbiome could also be influential in research into therapeutics for a variety of diseases, including Parkinson’s. And recently, its potential has been recognized.

Given the dynamic microbial composition of the gut, it is important to understand their ability to become drug targets, especially in precision medicine – treatments that are tailored to individuals based on their genetics and lifestyle. Conditions such as irritable bowel syndrome, diabetes, obesity, autoimmune diseases such as rheumatoid arthritis, and even some types 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-therapy along with immune checkpoint inhibitor therapy, to enhance the immune response in patients with melanoma who are less likely to respond. good for immunotherapy.

Like cancer, research into the gut microbiome therapy is ongoing for a variety of diseases. And new findings suggest that the gut microbiome may even transform medications for neurodegenerative diseases like Parkinson’s disease (PD).

But how exactly is the gut microbiome related to brain function?

Since microbes play an important role in the function of a strong intestinal wall, when the intestine is unhealthy, nutrients fail to be absorbed, while toxins are absorbed by the digestive system. This creates a profound inflammatory reaction, which then spreads throughout the body, including the brain, according to Dr. Raphael Kellman, Physician of Functional Medicine at the Kellman Wellness Center in the US.

“There is incredible communication between the gut, the microbiome and the brain. It’s called a two-way highway, meaning there’s communication from the microbiome to the brain, then from the brain to the microbiome,” said Kellman.

Parkinson’s and disturbed microflora

The way the brain and microbiome communicate is through neurotransmitters – messengers that carry chemical signals from neurons to other cells in the body. Serotonin and dopamine are two brain chemicals that control body movements and regulate digestive function. Both are related to emotional processing and mental health, and the lack of the latter, is responsible for many of the symptoms of Parkinson’s.

Just like the brain, the gut produces dopamine and serotonin, the microbiota’s means of connecting with the brain. Kellman regards the gut microbiome as complicated software that can send messages throughout the body, and which “artificial intelligence can never replicate”.

Another pathway for signal transmission is the immune system, where the microbiome sends a message to the immune system, after which the message is passed on to the brain.

And in a healthy gut, brain function reaches its peak, where communication is strong and memory remains unaffected. “No brain fog, your ability, your motivation is very strong. Your ability to think optimally is perfect, executive function is excellent, you are in a good mood,” said Kellman.

However, when the intestinal microflora is disturbed, problems arise. A difference in the release of neurotransmitters is observed, and an alarm signal is transmitted, causing the brain to be in a state of stress. Meanwhile, the immune system can also convey a similar message, causing it to become overactive, thereby triggering inflammation.

“When there is too much activation of the immune system, it can start to damage neurons to the point where over time, it can lead to degeneration of different neurons in different parts of the brain. Now this degeneration, finally, manifests as various neurodegenerative diseases such as Parkinson’s disease, dementia, Alzheimer’s, and also poor cognitive function. But it really determines the stage of Parkinson’s disease,” said Kellman.

As the microbiome deteriorates, the immune system declines further, thus following a vicious cycle. Kellman said: “You can look at it as an ecosystem. The outdoor ecosystem should look beautiful, and you can see it growing with different shades of green. Now what’s going on outside of an unhealthy ecosystem… starts to fade, and you start to see the color, the brown variation. It’s a great metaphor for what’s going on in the inner ecology, the microbiome.”

This unfavorable intestinal environment is suggestive of Parkinson’s, which is often characterized by tremors, rigidity, difficulty with balance and coordination, and sometimes with cognitive impairment. As more than 10 million people are living with Parkinson’s disease, there is a need to accelerate research in gut microbiome-based therapies – a target that has just been discovered – even though most of the treatments focus on receptors in the brain.

The gut microbiome: a drug target for Parkinson’s?

A study conducted by the University of Alabama in the US, revealed that there is an imbalance in the gut microbiome of Parkinson’s disease. 30% of gut bacteria differed in people with Parkinson’s when compared to those who did not have the disease, proving a link between the two. There is an excess of pathogens, some indications of inflammation. Bacteria such as Bifidobacterium dentium, Actinomyces oris and Streptococcus mutans increased more than six times, while Roseburia intestinalis and Blautia wexlerae decreased drastically.

The link between gut flora and Parkinson’s disease shapes the ability of the gut microbiome to act as a drug target to combat and even delay disease progression.

According to Kellman, the gut microbiome, the root cause of neurodegeneration, is an ideal target for therapeutic research, and not the brain. He explains that a poor diet contributes greatly to the development and progression of Parkinson’s disease, and therefore, consuming fiber-rich foods can alter the health of the gut microbiome, and in turn, slow disease progression.

Healthy gut, healthy mind

Prebiotic foods – dietary fiber – such as jicama, kiwi, spinach, artichokes and asparagus, among others, which are usually consumed to reduce digestive problems, can improve the regulation of inflammatory processes. Eating fiber-rich superfoods increased the number of short-chain fatty acid (SCFA)-producing bacteria, which in the intestines of Parkinson’s disease, significantly decreased of its kind. SCFAs, which are produced by microbes in the gut when these fibrous foods are fermenting, can modulate the levels of neurotransmitters, thereby inhibiting the development of Parkinson’s.

“Not what we eat, to say, what does the microbiome eat?” says Kellman, who believes that taking supplements while detoxifying the gut can reduce inflammation. He explains that prolonged use of antibiotics, use of drugs such as proton pump inhibitors and overexposure to poisons, be they fungi or pesticides, can have a devastating effect on the microbiome.

After treating people with Parkinson’s, Kellman recounts that patients see greater results when their gut microbiome is treated, than when they are on conventional medication.

He said: “There isn’t a patient I’ve ever seen with Parkinson’s disease who hasn’t improved, some so incredibly, that you can remove that medical history from their chart.”

“This is a new reality that is happening behind the firewall that people don’t know about. And that’s why it’s so important to spread 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 kind of drug that’s evolving rapidly. Now.”

Apart from prebiotics, probiotics and psychobiotics are a sought after avenue that may provide encouraging results with respect to the treatment of Parkinson’s. Probiotics are live microorganisms that restore the gut microbiota, and psychobiotics, whose potential is being investigated, have benefits such as stimulating antidepressant effects, an emerging intervention in mental health research. Probiotics, such as Bifidobacterium species, Lactobacillus, and Streptococcus, may relieve symptoms of bloating and abdominal pressure in people with Parkinson’s disease, according to a 2022 study.

Another mechanism by which the gastrointestinal flora can suppress inflammation is through fecal microbiota transplantation (FMT). FMT – faecal transplant – is a technique in which the gut microbiota from a healthy donor is transplanted into the intestine of a patient, to reconstruct the flora in the gut that is not healthy. After proving 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 quality of life, mental health, and motor symptoms had improved in the individuals during the three months of follow-up. However, whether such therapy can have long-term beneficial effects remains to be further explored for Parkinson’s.

In addition to these therapies, recent research reveals how exosomes can treat Parkinson’s symptoms. Exosomes – extracellular vesicles that regulate immune cells and gut microbes – mediate α-synuclein transport in the brain. Misfolding of the α-synucleins group is a neuropathological feature of Parkinson’s disease. However to discover its full clinical potential, exosomes can act as biomarkers as well as vectors for Parkinson’s therapy.

While not a cure, Kellman believes that focusing on the gut microbiome for the treatment of Parkinson’s is the right approach.

“It’s not me who says this, science says this. This is the direction we should go, to see the best results. This is a new pathway to a new neurodegenerative disease, by healing the gut, by healing the microbiome. This is revolution.”