Parkinsons disease (PD) is the second most common neurodegenerative disorder, typified by resting tremors and the loss of dopaminergic neurons. It affects approximately 7 million people globally, and 1 million in the US.
According to the Braak model of progression of Parkinsons disease, the disease process commences in the lower brainstem in the dorsal motor nucleus of the vagus nerve, as well as anterior olfactory structures. From there it follows an ascending course up through the brain with little variation between individuals.
While most people know that motor symptoms, such as tremors, slow movements, rigidity and poor balance, are common in PD, many do not know that autonomic functions may occur before the motor symptoms. Autonomic functions are those that occur without thought, such as heart rate, digestion, elimination (more about that later in this article), breathing rate, perspiration, urination, and sexual arousal. Autonomic symptoms in Parkinsons disease can include postural low blood pressure, constipation, difficulty swallowing, abnormal sweating, urinary leakage, and sexual dysfunction.
The loss of these autonomic functions may be tied to loss of nerve fibers in the skin. In the early stages of PD, before electrophysiologic neuropathic changes occur, a recent study showed that both large and small nerve fiber density in the skin decreases. Loss of autonomic nerves to blood vessels, sweat glands, and other structures occurs causing, among other things, impairment of the sensory perception of applied physical pain, including increased ability to tolerate heat and pressure on the skin. The loss of sensory perception can be a safety concern.
The cause of PD is still a mystery, but it is possible that there is a gut-brain connection in PD via at least 2 mechanisms: transmission of prion-like particles up the vagus nerve, and lipopolysaccharide (LPS) production in the gut.
Related to the first mechanism involving the vagus nerve, many of the effects of the microbiota and/or probiotics on brain function have been shown to be dependent on the activation of the vagus nerve, the long nerve connecting the gastrointestinal (GI) tract to the brain. Although not proven conclusively, some scientists believe that in some cases, a problem in the gut travels through the vagus nerve to the brain, leading to PD.
Here is why: Most people have heard about the loss of dopamine neurons in PD cases. However, the hallmark of Parkinsons disease is the presence of clumps of alpha-synuclein, a protein in the brain. Scientists have found alpha-synuclein clumps in other parts of the body, including nerve cells in the gastrointestinal tract. Studies in animal models of PD have shown that clumps of alpha-synuclein in the stomach can travel through the vagus nerve, like proteinaceous infectious particles (prions), to reach the brain. People with severed vagus nerves have a less likely chance of developing Parkinson’s disease.
In mice raised to overexpress alpha-synuclein, transplantation with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. The researchers in this study said, "These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD."
Another study published in June, 2018 stated that both loss of dopaminergic (DA) neurons and aggregation of α-synuclein in the substantia nigra (SN) occur in the GI enteric nervous system in PD patients. They concluded that there was "powerful evidences about the prion-like propagation of α-synuclein" which supports the hypothesis of gut-brain axis in PD.
The second suspected mechanism in the gut to brain connection in PD is LPS. LPS is a toxin produced by Gram-negative bacteria. Animal model studies demonstrated that inflammation induced by LPS can cause symptoms similar to PD, including extensive activation of brain immune cells and selective loss of dopaminergic neurons in the brain. More about LPS and how probiotics protect against it is provided in my book, Probiotics: How to Use Them to Your Advantage, scheduled for release in March of 2016.
In addition to vagus nerve prion-like particle transmission and LPS toxicity, circumstantial evidence that there is a gut-brain connection involved in PD involves non-motor symptoms. Non-motor symptoms can precede the onset of PD by 10-20 years, and two of the most common non-motor symptoms of Parkinsons disease are constipation and seborrheic dermatitis.
Constipation is an obvious gastrointestinal condition. It has been shown that in PD, prolonged intestinal transit time and constipation, both related to autonomic dysfunctions, are associated with alpha-synuclein accumulation and neurodegenerative changes in the gut-associated nervous system. Also, signs of local inflammation, oxidative stress and increased mucosal permeability have been shown.
Seborrheic dermatitis is associated with the presence of Malassezia yeasts. The overabundance of these yeasts shows a disruption in the normal flora of the skin which, in turn, is related to the health of the gut.
Another common non-motor symptom of PD is depression, which can also have roots in the gut.
Other research has shown an important relationship between the
activity of the peripheral vagus nerve and the function of the dopamine
system in the brain in rats. Postmortem studies on humans demonstrated
that the brain area known as the dorsal motor nucleus of the vagus,
which is connected to GI symptoms, was affected in the early stages of
The alpha-synucleins are also present in a number of other neurological brain pathologies, such as multiple system atrophy, dementia with Lewy bodies, many cases of Alzheimer’s, a subtype of essential tremor and others. Perhaps there is a link with the GI tract in these other pathologies.
It has been shown in multiple studies that people with PD have skewed microbiota. One study published in November, 2016 showed that fecal short-chain fatty acids in patients with PD were significantly reduced compared to controls. Researchers are following study participants to find
out if their gut microbiology changes over time and if these potential changes
can lead to improved prognosis of the disease. Stay tuned for updates!
What is known at this time is that the factors of probiotics, diet and lifestyle can help with LPS reduction and with the non-motor symptoms of Parkinsons disease such as constipation, depression and dermatitis. I can help guide you through improvement of those factors with nutritional consultations.
Read more about constipation and probiotics here.
Read more about depression and probiotics here.
Go to the page on other health conditions.
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