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Leaky Gut And Parkinson’s

But How Does A Bad Microbiome Produce Parkinsons

The role of gut flora in Parkinson’s disease

A 2017 study has revealed at least one of the major reasons why the gut microbiome can produce Parkinsons. Researchers from the University of Alabama at Birmingham tested 197 Parkinsons disease patients along with 130 healthy control subjects. To offset for local diets, the study tested people from the South, people from the Northeast and people from the Northwest. The researchers tested each persons gut bacteria and analyzed the different species that populated each persons gut.

The findings were eye-opening.

First, the study once again established that Parkinsons disease patients have abnormal populations of gut bacteria compared to healthy people. But it was the particular species of bacteria that became the most revealing aspect. Dr. Haydeh Payami, a neurology professor in the school of medicine at the University of Alabama explained:

Our study showed major disruption of the normal microbiome the organisms in the gut in individuals with Parkinsons.

The researchers found that probiotic species that are involved in helping the body remove toxic chemicals from the body were glaringly low among the Parkinsons disease patients. Probiotic families at lower levels included:

Bifidobacteriaceae Pasteurellaceae Verrucomicrobiaceae

This is significant. Why? Because other research has linked Parkinsons disease to the exposure of chemicals in pesticides and other consumer products.

Gut Microbiome And Metabolic Changes In Parkinsons Disease

With increased accessibility to next-generation sequencing technologies, there has been an expansion of studies showing significant, albeit varying, differences in the gut microbiome in PD compared to non-PD controls. These have recently been reviewed by Lubomski et al., ,

Interestingly, several 16S rRNA gene-sequencing studies have shown significantly reduced abundances of butyrate-producing bacteria in PD fecal samples compared to controls.- These findings were supported by a quantitative real-time polymerase chain reaction study targeting butyrate synthesis genes and a gas chromatography study demonstrating significantly reduced fecal levels of short-chain fatty acids in PD patients versus controls. SCFAs are thought to play a key role in microbiotaâgutâbrain crosstalk, in part via the regulation of bloodâbrain barrier integrity, neuronal survival, inflammatory cascades, and endocrine signaling. Butyrate in particular is a major energy substrate for the colonic epithelium and acts to improve gut barrier function. Being a histone deacetylase inhibitor , butyrate has been found to exert neuroprotective actions in experimental PD models,, including the mitigation of PD motor impairment and dopaminergic cell death.-

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Fecal And Plasma Levels Of Different Types Of Scfas In Patients With Pd And Controls

Patients with PD had significantly lower fecal concentrations of acetic acid , propionic acid , and butyric acid than controls . In contrast, plasma concentrations of circulating propionic acid , butyric acid , and valeric acid were increased in patients with PD compared to controls .

Violin plot shows data density and median with interquartile range for fecal levels of acetic acid , propionic acid , butyric acid , and valeric acid in patients with Parkinson disease and unaffected controls. Mean ± SD is shown. *p< 0.05, **p< 0.01.

Violin plot shows data density and median with interquartile range for plasma concentrations of acetic acid , propionic acid , butyric acid , and valeric acid in patients with Parkinson disease and unaffected controls. Mean ± SD is shown. *p< 0.05, **p< 0.01.

We first examined the possible influence of age on fecal and plasma SCFA levels. We found that age did not correlate with either measure for the individual SCFA types, except for plasma levels of isovaleric acid modestly correlating with age in controls . There were no significant correlations between fecal and plasma levels of the individual types of SCFAs . We further observed that plasma levels of acetic acids correlated with IFN-γ and showed a trend with TNF-α plasma levels of butyric acids tended to correlate with IFN-γ .

Receiver Operating Characteristic Association Statistics for Predicting Development of Parkinson Disease

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Low Mood And Mood Disorders

The gut microbiome plays a huge role in our mood and mental stability as well, and even the development of some mental health disorders . Because changes in microbiota correlate to changes in brain chemistry, a gut microbiome disruption due to illness, antibiotics, etc., can be associated with abnormal behavior and cognition, including mood disruption, depression, and anxiety . If this change in the microbiome causes leaky gut and thus weakens the mucosal lining and increases permeability, inflammation can be another driver of mood disruption . And unfortunately, just as hyperpermeability can be cyclical, inflammation can also be both a cause and result of depression .

Gut Microbiome Species Correlate With Plasma And Fecal Levels Of Scfas

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Metagenomic analysis of gut microbiome species showed that the bacterial richness within each sample tended to be higher in patients with PD than in healthy controls , which are consistent with previous studies. The principal coordinates analysis revealed that patients with PD had different gut microbiota composition from healthy controls .

We further explored the correlations between the relative abundance of gut microbiota and fecal or plasma levels of SCFAs. Heat maps representing Spearman correlations for the relative abundance of differential bacteria and SCFA concentrations in feces or plasma revealed that fecal levels of acetic acid, propionic acid, and butyric acid all correlated with the abundance of Bacteroides sp AM16-15 and Bacteroides sp AM25-34 in control participants . However, we did not find these positive correlations in patients with PD . Among patients with PD, the abundance of proinflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, especially propionic acid . Of note, plasma propionic acid levels were associated with PD occurrence and with motor symptom severity . Furthermore, the abundance of Ruminococcus sp AM28-29LB consistently correlated with reduced fecal levels of all SCFAs and increased plasma butyric acid , which was associated with cognitive decline in PD .

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What Is The Microbiome

Your body houses a collection of microscopic organisms, called your microbiome, which includes trillions of bacteria, fungi, viruses, and other microbes.

Most of your microbiome is found in your intestines and colon, also known as your gut, and these gut bugs do a lot!

Theyre responsible for digesting food, starting immune system responses, guard against infections, remove toxins from your body and produce a host of vitamins and neurotransmitters that are critical for daily function and health .

Your gut microbiome is as original as your fingerprint, but there are certain combinations of microbes that are the hallmarks of a healthy gut . Good and bad bacteria, for instance, are both found in a healthy gut but work in symphony. This is called gut symbiosis. Problems can surface when bad bacteria, fungi, viruses, or parasites disrupt this balance, often referred to as gut dysbiosis.

A disruption in the gut microbiota can cause the intestinal lining to break down, allowing toxins and other foreign substances to pass through the gut lining and into the bloodstream triggering a systemic inflammatory response. This breakdown of gut lining is referred to as leaky gut syndrome.

Central Nervous System Lymphatics

Louveau et al56 discovered a network of lymphatic vessels lining dural sinuses carrying both fluid and immune cells from cerebrospinal fluid. This observation opens the door to the possibility that cytokines from the GI tract may interact more with the CNS than previously understood. Any microbial dysbiosis that potentially triggers an inflammatory cascade in the CNS can potentially cause dysfunction of the immune system, leading to the development of neurodegenerative diseases like PD.

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Probiotics Also Help Brain Function

The link between the gut and the brain is no longer that big of a reach. For years, scientists have been investigating the gut-brain axis connection. Many mood-related and neurological conditions have now been linked with gut bacteria.

Other research has found that probiotic bacteria can increase levels of important neurotansmitters such as dopamine and serotonin. More specifically, a reduction of dopamine and its related norepinephrine is one of the hallmark symptoms of Parkinsons disease. When there isnt enough dopamine to provide smooth nerve impulses between the parts of the brain that control motor movement, coordination and motor control begin to deteriorate.

One of the greatest suppliers of dopamine within the brain is the substantia nigra. During the progression of Parkinsons, neurons in this part of the brain are damaged, which decreases the availability of dopamine. This damage is often related to the existence of Lewy bodies within these areas so it is assumed Lewy bodies are involved in the progression of Parkinsons.

I might add that University of Nebraska researchers also linked increased levels of Lewy bodies with increased pathogenic bacteria in the gut.

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Intriguingly, however, the New Scientist article also revealed that other hormone activity in the gut can indirectly influence the production of dopamine in the brain too:

“Stress also leads the gut to increase its production of ghrelin, a hormone that, as well as making you feel more hungry, reduces anxiety and depression. Ghrelin stimulates the release of dopamine in the brain both directly, by triggering neurons involved in pleasure and reward pathways, and indirectly by signals transmitted via the vagus nerve.”

Again, none of my health professionals have ever mentioned ghrelin to me before – I will write a sequel post on what I discovered about this. However, here I would like to underline the point that many people with PD experience “blocking” of their medication after large or hard to digest meals, and now the above helps make sense of this: hunger is a way to stimulate the Vagus Nerve and hence to promote the relaxational “feel good” state of the body, increasing the system’s call on conversion of PD drugs into dopamine in the brain.

“Nevertheless, nerve signals sent from the gut to the brain do appear to affect mood. Indeed, research published in 2006 indicates that stimulation of the vagus nerve can be an effective treatment for chronic depression that has failed to respond to other treatments .

The New Scientist article links these findings directly to PD – because the gut as well as the brain becomes short of dopamine supplies :

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Dive Deep: The Link Between Parkinsons And The Gut

We have discovered for the first time a biological link between the gut microbiome and Parkinsons disease. Sarkis Mazmanian, Caltech

Since we launched our podcast episodes on the neuroscience of Parkinsons and a Parkinsons diagnosis, weve had requests for more information on the link between Parkinsons and the gut.

While great strides have been made in determining the origins of Parkinsons in the body and the link between Parkinsons and the gut, there is still a long way to go.

If youre interested in learning more about this topic, weve rounded up some of the best articles and newest research on the subject so you can dive deep.

Does Parkinsons Begin in the Gut? May 8, 2018

Around half of the people diagnosed with Parkinsons experienced constipation prior to their diagnosis and before their first motor-symptoms began, which makes the move toward more studies that focus on the link between the gut and Parkinsons an exciting one. Especially when you consider what it could mean for treating Parkinsons in the future. This article outlines the workings of the gut-brain highway, the role inflammation plays in Parkinsons and some of the treatments currently being tested.

To learn more about inflammation and viruses that infect and replicate bacteria in those with Parkinsons, read this. And for more on inflammatory bowel disease, read this.

The Gut-Brain Axis in Parkinsons Disease: Possibilities for Food-Based Therapies December 15, 2017

If Youve Already Been Diagnosed With Parkinsons The Health Of Your Gut Still Matters

Studies in mice have found that the composition of the gut microbiome significantly impacted motor symptoms . In the largest study of small intestinal bacterial overgrowth and Parkinsons, researchers found SIBO was present in 25% of people diagnosed with Parkinsons and independently predicted worse motor function .

Constipation- likely due to slowed gut motility in combination with gut dysbiosis and poor dietary habits – is a non-motor symptom that has been reported up to 20 years before a Parkinsons diagnosis , and can significantly decrease the effectiveness of Parkinsons medications.

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Cognitive Decline And Memory Disorders

Cognitive decline and memory disorders, like dementia and Alzheimers disease, are known to be caused by the degeneration of brain tissue, and reduced function and plasticity . Toxins that are leaked from the gut and blood-brain barrier and attach to vulnerable neurons, chronic inflammation due to leaky gut, and the immune systems response to that chronic inflammation can all contribute to this degeneration . Beyond that, the dysregulation of the gut microbiome that preludes leaky gut can also lead to disruption of the guts secretion of different types of brain chemicals and proteins, such as brain-derived neurotrophic factor . Disruption or decrease in the levels of BDNF can reduce brain plasticity, development, and even affect the brains physical structure . This can lead to issues with memory and learning and is associated with neurodegeneration and the development of dementia and Alzheimers .

Implications For Parkinson’s Disease

leaky gut leaky brain

The 2012 New Scientist article referred to above also states:

“If nothing else, the discovery that problems with the ENS are implicated in all sorts of conditions means the second brain deserves a lot more recognition than it has had in the past. ‘Its aberrations are responsible for a lot of suffering,’ … a better understanding of the second brain could pay huge dividends in our efforts to control all sorts of conditions, from obesity and diabetes to problems normally associated with the brain such as Alzheimers and Parkinsons.”

“Yet the number of researchers investigating the second brain remains small. ‘Given its potential, its astonishing how little attention has been paid to it,’ “

Unfortunately, this is what I found to be the case, too. Nevertheless, I hope by sharing what has been gleaned so far, this will help inform people with PD that they do need to pay particular attention to digestive health as well, and to be very careful about what they eat!

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Second Variant Of Parkinson’s Disease That Begins In The Gut Is Identified

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Leaky Blood Brain Barrier And Parkinson’s Disease

which explains how both the blood brain barrier and the gut lining can lose their protective functions in a variety of ways. Given that leaky gut and leaky brain are both heavily implicated in the disease, the road blocks between chemicals produced in the gut reaching the brain is not so assured for people with Parkinson’s. For example, unusually high levels of histamine, which is naturally produced in the gut as part of digestion, have been found in the brains of people with PD

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The Overlaps Between Stress And Parkinson’s Disease Part 2

for detailed articles about the central role of the Vagus Nerve and fight-flight-freeze stress responses in Parkinson’s Disease. Note also the studies which show that, when the Vagus Nerve was surgical severed, this provided a significant protective factor for preventing Parkinson’s Disease – strongly suggesting that the communication of gut problems via the ENS to the autonomic nervous system is linked to PD onset.

“The ENS is capable of carrying reflexes and acting as an integrating center completely independently. The sensory neurons report on mechanical and chemical conditions. Through intestinal muscles, the motor neurons control peristalsis and churning of intestinal contents. Other neurons control the secretion of enzymes.”“The enteric nervous system also makes use of more than 30 neurotransmitters, most of which are identical to the ones found in the brain, such as acetylcholine, dopamine, and serotonin. More than 90% of the body’s serotonin lies in the gut, as well as about 50% of the body’s dopamine.”

Defining The Parkinson’s Microbiome Strengthens Links To Gut Health

Postbiotics an emerging path towards precision health

npj Parkinson’s Disease

Researchers from the Quadram Institute have carried out a meta-analysis of the gut microbiome in Parkinson’s disease, giving the clearest picture to date of the changes associated with the condition.

By re-analyzing data from ten different studies, a common pattern of changes in the abundance of bacteria types in Parkinson’s disease emerges, suggesting that the alteration in the gut microbiome might trigger some of the gastrointestinal problems seen in patients.

Parkinson’s is a progressive condition that affects nerve cells that produce dopamine, which coordinates movement. As more nerve cells die, less dopamine is produced, leading to gradually worsening tremors, slower movement and muscle stiffness.

In addition, many people with Parkinson’s disease have gastrointestinal problems that can show several years before the physical movement symptoms. They may also have inflammation and “leaky” gut, signs of an imbalanced gut microbiome.

These observations have prompted genome sequencing studies to identify the types of bacteria in the microbiome of people with Parkinson’s disease, and compare that with people without the condition.

The meta-analysis, published in the journal npj Parkinson’s Disease, confirmed that the Parkinson’s microbiome is different with a reduction in the dominant bacteria usually found in a healthy human gut.

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