Parkinson's disease affects millions globally and leaves a devastating impact on individuals and their families. Recent scientific studies have brought to light a novel link between Parkinson's and the gut microbiome, suggesting that microbial diversity and dysbiosis play a significant role in the disease's progression.
In this thought-provoking piece, we explore the intricate relationship between gut-brain communication and the microbiome to understand better the different ways the gut might influence Parkinson's.
We dive into the latest research on how a microbiome imbalance might contribute to disease development, including the role of gut-dependent immune system dysfunction. By uncovering crucial insights, we aim to paint a more comprehensive picture of the importance of gut microbiome-targeted therapies in the management and prevention of Parkinson's.
In an essay on shaking palsy, James Parkinson was the first to provide a clear medical description of Parkinson’s in 1817. Dr. Parkinson believed it to be a neurological syndrome due to damage to the spinal medulla. But it was Dr. Brissaud who first proposed damage to the substantia nigra as the anatomical source of Parkinson’s.
Science has since come a long way from believing Parkinson’s to be a result of damage to the spinal medulla to defining it as a progressive neurodegenerative disease due to a loss of dopamine-producing nerve cells in a part of the brain responsible for motor function and movement.
What is Parkinson's and who does it affect?
Symptoms of Parkinson’s disease (PD) display motor dysfunction such as resting tremors, rigidity, bradykinesia - slow movement, hypokinesia - limited range of movement, altered gait, and difficulty balancing. Patients with PD begin to experience some non-motor symptoms such as chronic constipation long before they notice any motor dysfunction.
Most people diagnosed with Parkinson’s are over the age of 60 and it’s estimated to affect twice as many men than it does women. But women tend to display a faster progression of the disease than men.
When and where does Parkinson's start?
Research has been ongoing for decades trying to establish the point of onset for Parkinson’s. Numerous neurodegenerative diseases are believed to be a result of the toxic accumulation of protein aggregates in the brain.
In the case of Parkinson’s, α-Synuclein aggregate deposits in the brain are believed to trigger a cascade of events that might lead to dopamine-producing neuronal cell death leading to progressive motor deficits in the body. Yet α-Synuclein is an antimicrobial peptide so it is more likely reacting to some pathogen/s than being a cause in itself.
Sporadic and Familial PD
Although, the vast majority of PD cases occur sporadically, roughly 10% of the cases might be attributed to genetic mutations related to the SNCA gene - the gene responsible for the production of α-Synuclein (aSyn) protein. As it stands, it's largely accepted that the accumulation of aSyn clumps in dopaminergic cells leads to cell death in the brain. But what remains contested is the leading cause that initiates aSyn accumulation.
Before we explore the role of the gut microbiome in the onset of Parkinson’s, let's take a quick peek into the Parkinson's brain.
Substantia Nigra, a-synuclein aggregates, neuron death
Different parts of the brain control and manage different functions in the body. Neurons (nerve cells) are the functional cells of the brain that fire information from one neuron to another with the help of neurotransmitters such as dopamine and GABA (Gamma-aminobutyric acid).
Substantia Nigra is a part of the brain that controls movement. It consists of neurons that use dopamine as a way to communicate with one another to either initiate or inhibit motor function. Although aSyn (protein) is found in its free form in the neurons of a healthy brain, its function is poorly understood. In a Parkinson-affected brain, misfolded aSyn clumps together, which along with other proteins then form something known as Lewy bodies. There’s ongoing research into how aSyn aggregation has a neurotoxic effect that progresses to cell death. But according to the results of a study published in 2019, aSyn accumulation might lead to compromised mitochondrial function leading to less energy production in the affected neuron and increased production of ROS (reactive oxygen species) resulting in malformed and compromised mitochondria, leading to neuronal death. Following cell death, fractions of aSyn aggregates might spread to neighboring cells and seed them, leading to progressive neuronal death and compromised motor function.
Is Parkinson's linked with gut health?
There are various hypotheses regarding the onset and progression of Parkinson’s. Researchers have been trying to understand which factors trigger aSyn aggregation in nerve cells and treat it as the anchor point for further research. Since the first Parkinson’s microbiome research was published by Dr. Filip Scheperjans in 2014, there have been 100’s more studies advancing the gut-brain connection and PD.
One of the hypotheses is that aSyn aggregation first starts in the gut and spreads upstream into CNS via the vagus nerve, ultimately reaching the brain.
Gut microbiome, ENS, and the gut-brain axis
The gut microbiome consists of trillions of microbes that may have helpful or harmful effects. Collectively, the microbial genetic material contains more genomic DNA than the human genome itself, allowing the gut microbiome to synthesize bioactive compounds that are essential for the host. Many of the compounds are critical neurotransmitters.
The enteric nervous system (ENS) is the part of the nervous system that regulates the digestive system and connects to the central nervous system (CNS) via the vagus nerve and other pathways. ENS has been estimated to contain more neurons than the whole of the spinal cord and is known as the second brain or the gut-brain. The gut-brain axis is a bidirectional communication system that allows the brain and gut microbiome to communicate with each other to regulate functions such as intestinal motility and gut barrier impermeability.
The gut microbiome has a very delicate balance where different bacterial species compete with each other for resources. Several studies point toward a causal relationship between an imbalance in the gut microbial diversity known as gut dysbiosis and Parkinson’s.
Dysbiosis and Parkinson’s
Both helpful and harmful bacteria form a diverse and competitive gut environment. The diversity and balance of the gut microbiota are easily susceptible to changes in diet, antibiotic treatment, environment, and lifestyle. While two dominating phyla, Bacteroides and Firmicutes, make up roughly three-quarters of the gut microbiome, the rest is made up of a variety of other microbial Phyla like Actinobacteria and Proteobacteria. An imbalance in the gut microbiome that leans toward a rise in pathogenic bacteria is known as gut dysbiosis.
Dysbiosis led inflammation, gut barrier permeability, microglial activation, and aSyn accumulation
A healthy gut microbiome supports a semipermeable gut barrier that allows functions such as nutrient absorption and electrolyte exchange but prevents the gut microbiome, microbial metabolites, food, and bacterial toxins from entering the blood circulation.
According to several 16s rRNA gene-sequencing studies in PD patients, there’s a significant decrease in butyrate-producing bacterial species such as the Butyricicoccaceae family in PD patients. Butyrate is a short chain fatty acid that results from bacterial fermentation of complex fibers and is known to be utilized by gut epithelial cells as an energy source.
Butyrate and other SCFAs are also critical in the regulation of intestinal barrier permeability, SCFAs can also cross the blood-brain barrier and have a neuroprotective effect on cell survival and according to studies can mitigate PD motor dysfunction and dopaminergic cell death.
Dysbiosis-led changes in bacterial diversity might weaken the gut barrier allowing a leaky gut. The cell walls of Gram negative bacteria are made of lipopolysaccharide which is a known inflammatory compound that can cross this barrier and enter the blood stream. Mucosal immune cells in the gut barrier release inflammatory cytokines (immune messenger proteins) in response to a barrier breach that can lead to gut inflammation.
Toll-like receptors (TLRs) are immune cells that recognize a pathogenic breach and initiate an inflammatory immune response. Gut dysbiosis acts as a constant trigger to the TLRs and thus the immune system leading to systemic inflammation. Studies point to gut inflammation as a marker associated with PD and a-Syn accumulation in the gut. In fact, several markers of inflammation have been elevated in PD.
Gut inflammation has been suggested as a possible cause of neuroinflammation and neurodegeneration. A study in mice suggests that an interaction between TLR4 and aSyn can trigger microglial activation (immune cells in the brain) associated with Parkinson’s disease.
Can probiotics have a protective effect on Parkinson's?
As more and more research points towards gut dysbiosis as the hub of onset for Parkinson's, novel therapeutic options such as the potential use of probiotics to manage gut dysbiosis are being explored.
Probiotics are live helpful bacteria that might have a positive effect on the gut microbiome. A study into the effect of prebiotic and probiotic supplements in constipation linked with Parkinson’s in 120 PD patients over four weeks found an increase in total bowel movements when compared to the control group. The probiotic supplement contained bacterial strains such as S. salivarius, subsp. thermophilus, E. faecium, L. rhamnosus GG, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii, subsp. bulgaricus, and Bifidobacterium. Similarly, a randomized, double-blind placebo-controlled trial found an improvement in PD symptoms and a significant reduction in MDS-UPDRS (clinical marker in PD) after a probiotics supplement administration for 12 weeks.
The mix of probiotic strains administered in this trial consisted of L. acidophilus, B. bifidum, L. reuteri, and L. fermentum. In a study conducted in a PD mouse model, supplementation with L. plantarum PS128 improved motor function, increased levels of dopamine, reduced neuron loss, microglial activation and inflammatory factors as well increased the expression of BDNF – brain derived neurotrophic factor. Reduced levels of BDNF have been reported in neurological conditions such as Alzheimer’s and Parkinson’s. Optimal levels of neurotrophins such as BDNF prevent cell death and support neuronal growth and maturation as well enhancing the function of compromised neurons in Alzheimer’s and Parkinson’s.
Probiotics, and gut health
Hippocrates’ “all disease begins in the gut” takes on new meaning when we look at emerging research pointing to the gut as the point of origin for a number of neurological diseases.
A progressive neurodegenerative disease such as Parkinson’s doesn’t only take a toll on the emotional and mental health of an individual but also on their families. Protecting and supporting your gut health becomes vital as the average age of the world increases and the number of people affected with neurological disorders rises.
One of the easiest and most direct ways to support your gut health is to eat an ample amount of prebiotic and probiotic foods. Probiotic supplements such as our Ideal Immunity are rich in strains such as B. bifidum, L. plantarum, and L. reuteri that might confer benefits such as strengthening the gut lining, reducing inflammation, and having antioxidant activity.
Check out our blog to learn more about how probiotics might help you live an optimal life!
FREQUENTLY ASKED QUESTIONS
Can microbiome and Parkinson's be connected?
How do you support a healthy microbiome if you have Parkinson's disease or are concerned about your family history with Parkinson’s?
Martha Carlin, is a “Citizen Scientist”, systems thinker, wife of Parkinson’s warrior, John Carlin, and founder of The BioCollective , a microbiome company expanding the reach of science and BiotiQuest, the first of it’s kind probiotic line. Since John’s diagnosis in 2002, Martha began learning the science of agriculture, nutrition, environment, infectious disease, Parkinson’s pathology and much more. In 2014, when the first research was published showing a connection between the gut bacteria and the two phenotypes of Parkinson’s, Martha quit her former career as a business turnaround expert and founded The BioCollective to accelerate the discovery of the impact of gut health on all human disease. Martha was a speaker at the White House 2016 Microbiome Initiative launch, challenging the scientific community to “think in a broader context”. Her systems thinking background and experience has led to collaborations across the scientific spectrum from neuroscience to engineering to infectious disease. She is a respected out of the box problem solver in the microbiome field and brings a unique perspective to helping others understand the connections from the soil to the food to our guts and our brains.
Did you know that recent studies show people with poor gut diversity had lower quality of life? The health of your microbiome impacts your mental health, sleep, energy, the risk for chronic illnesses, and much more. A probiotic breakfast can...
Intermittent fasting (IF) may have started as a fitness trend for weight loss, but today it's a go-to lifestyle choice for many. Practicing intermittent fasting has been linked with health benefits such as lowering blood sugar and insulin, preventing heart...