Parkinson’s is characterised by symptoms such as body tremors, rigidity and lack of balance, as well as psychological symptoms including depression, anxiety and insomnia. It is a progressive neurological disorder, caused by damage to nerve cells located in a part of the brain called the substantia nigra. Cells located here are responsible for producing a neurotransmitter called dopamine, which acts as a messenger between the brain and the rest of the body to help coordinate movement and balance, as well as many other things.
How Common is Parkinson’s?
Currently in the UK, around 1 in 500 are affected by Parkinson’s, meaning there are an estimated 127,000 people living with the condition. Figures show that Parkinson’s is on the rise – In 2016, an estimated 6.1 million people across the planet had Parkinson’s, more than double compared to figures in the 1990s. Scientists still have yet to understand the exact cause of this disease, however, it is thought that there are genetic and environmental links, such as industrial pollution that can play a key role in the development of this disease. However, in the past few years there has been an explosion of research that points to imbalances in the gut as an influencing factor in the development of Parkinson’s.
How Does the Gut Play a Role in Parkinson’s?
Around 200 years ago an English surgeon named James Parkinson reported that some patients with Parkinson’s also suffered with constipation and that by treating digestive complaints, some of the physical symptoms associated with the neurodegenerative disease were relieved. Since then, constipation has been noted as one of the most common non-motor symptoms related to Parkinson’s, witharound half of patients experiencing constipation which often precedes the diagnosis of this neurodegenerative disease. Much of today’s research therefore lies in investigating the question of where the pathogenesis of Parkinson’s initiates: is it the gut or the brain?
Lewy Body Pathology
One of the hallmarks of Parkinson’s is abnormal aggregates of proteins that develop inside nerve cells, in both the brain and the peripheral nerves, called lewy bodies. In particular, it is the misfolding of the major constituent of lewy bodies, known as alpha-synuclein that causes symptoms related to Parkinson’s. Researchers have found that when this occurs, it catalyses an almost infection-like process, whereby the behaviour of misfolding spreads from cell to cell.
Aggregates of alpha-synuclein have been found in the enteric nerves of Parkinson’s patients, which is an almost autonomous part of the nervous system located in the digestive tract, that orchestrates gastrointestinal behaviour.Research shows that the pathological process may therefore begin in the gut within the enteric nerve cells, which spreads to the central nervous system (spinal cord and brain). In a study where α-synuclein was injected into the intestinal walls of rats, researchers found that α-synuclein was transported via the vagus nerve to the dorsal motor nucleus of the vagus in the brainstem, leading to damage to the dopamine-producing cells in the brain. This theory has been further confirmed by studies showing how vagotomy patients that have had their vagus nerve severed, have less risk of neurodegeneration than those who don’t. However, the question of how changes in the intestines drive neurodegeneration in the brain remains an active area of investigation and there are other theories that are being explored, such as how inflammation in the gut and alterations in the flora (bacteria) of the gut can trigger the pathogenic process of Parkinson’s disease.
The Gut Microbiome and Parkinson’s
It has been suggested that changes in the gut microbiota, due to inflammation, may trigger the misfolding of α-synuclein. The intestines are inhabited by tens of trillions of microorganisms, including more than 1000 species of bacteria – both commensal (friendly) and pathogenic (unfriendly) – and studies suggest that the ratio between the two can significantly impact permeability and function of the intestinal barrier, affecting the immune system by activating enteric glial cells and neurons, and causing inflammation.
In a study where mucosal biopsies and fecal samples were collected from a group of patients with Parkinson’s disease and a control group, researchers found that in those that don’t have PD (control group), there were higher levels of commensal bacteria that produce butyrate, a fatty acid compound that is known for its anti-inflammatory properties. This fatty acid, that is produced by bacteria through the break down of fibre, is important for helping to modulate T-regulatory cells, which play an important role in preventing autoimmunity and intestinal permeability. The researchers concluded from this study that dysbiosis (imbalance of bacteria) in the gut, triggers a pro-inflammatory state and leads to the misfolding of α-synuclein.
Another interesting study, using mice that were genetically engineered to be more susceptible in developing Parkinson’s, found that in those that were colonised with gut bacteria from PD patients, rather than from healthy subjects, there was enhanced neuroinflammation and motor symptoms. This further suggests that dysbiosis of the gut leads to the neuropathogenesis of Parkinson’s.
Why is it important to support the gut microbiome?
Research shows how the gut microbiota is very sensitive to antibiotics, heavy metals, persistent organic pollutants, pesticides, nanomaterials, and food additives. It is well known that microbial diversity is adopted within the first few hours of after birth and is then shaped over time as food is properly introduced and the immune system develops. Various factors such as exposure to xenobiotics (environmental pollutants), antibiotic therapy, diet and lifestyle, can all play a pivotal role in shaping the gut microbiota to make every individual microbially unique. As bacteria play an important role in protecting and maintaining the cells based in the enteric nervous tissue, as well as the immune system and the integrity of the gut barrier, it is therefore incredibly important to both avoid unnecessary exposure to toxins and eat a diet that supports a healthy flora.
Mounting evidence links exposure to xenobiotics to an increased risk of developing diseases such as Parkinson’s. There have been many animal studies that prove this, and now some human studies have begun to actually look into specific compounds, mainly pesticides, that play a role in the pathogenesis of Parkinson’s. Studies have shown that Organochloride pesticides are most commonly associated to Parkinson’s in comparison to others, and despite the fact that many of these were banned years ago, it is well known that these chemical compounds are very resistant to break down in soil and so can remain in the food chain for a long time. A study investigating the link between two pesticides known as rotenone and paraquat, showed how people who reported use of either one of these pesticides were 2.5 times more likely to develop Parkinson’s than those who hadn’t. This is one of many that demonstrate the risks of environmental pollutants and the development of neurodegeneration and although the mechanism is not yet understood, there are clear correlations that must not be overlooked.