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The Digestive Tract and Parkinson's Disease: A Possible Link

Linda Crampton is a writer and teacher with a first-class honors degree in biology. She often writes about the scientific basis of disease.

Parkinson's disease affects the substantia nigra in the brain.

Parkinson's disease affects the substantia nigra in the brain.

A Disease That Might Start in the Gut

Parkinson’s disease is a neurodegenerative disorder that primarily affects movement. It’s chronic and progressive, although the severity of the symptoms and the speed of deterioration vary in different patients. The disease involves specific brain changes. These include loss of dopamine and the appearance of Lewy bodies containing tangles of a protein called alpha-synuclein.

There is a growing suspicion that the digestive tract also plays a role in Parkinson's disease. Some evidence suggests that the disease may begin in the digestive tract and reach the brain later. Understanding the cause of the disorder could lead to the creation of better treatments.

An Overview of Parkinson's Disease

Parkinson's disease is named after James Parkinson, a Scottish physician. In 1817, he published an article entitled "An Essay on the Shaking Palsy" in which he described the typical symptoms of Parkinson's disease. The disease was eventually renamed in his honour. Today it's also known as Parkinson's or as PD.

Some common symptoms of the disease are listed below. A particular patient may not have all of the symptoms. In addition, the symptoms that are present may indicate the presence of a different health problem. Anyone who has the symptoms should visit a doctor for a diagnosis and treatment recommendations.

  • muscle tremors
  • slow and difficult movement
  • balance problems
  • rigid muscles
  • difficulty in speaking
  • difficulty in writing

Non-motor symptoms may also be present, including:

  • mood disorders
  • cognitive problems
  • problem related to sleep
  • vision problems
  • changes in the ability to smell and taste
  • urinary frequency
  • fatigue
  • constipation

James Parkinson was born on April 11th, 1755. Today April 11th is known as World Parkinson's Day. The event is designed to raise awareness of the disease.

The cell body of a neuron (or nerve cell) contains the nucleus. The axon is an extension that sends information to another neuron via a synapse.

The cell body of a neuron (or nerve cell) contains the nucleus. The axon is an extension that sends information to another neuron via a synapse.

Dopamine Loss and Lewy Bodies

Researchers have discovered that a region of the brain called the substantia nigra is affected in people with Parkinson's disease. The region is normally dark in colour due to the presence of a pigment called neuromelanin.

In PD, neurons in the substantia nigra that normally produce dopamine die or no longer do their job. Dopamine is a neurotransmitter, or a chemical that transmits a signal from one neuron to another. Neuromelanin production is linked to the production of dopamine, so the substantia nigra becomes lighter in colour as dopamine production decreases in people with PD.

Another brain change is the appearance of Lewy bodies and Lewy neurites inside neurons. Lewy bodies are relatively large, roughly spherical to oval structures. They are found in the cell body of a neuron. Lewy neurites are long and narrow structures that are located in the axons of neurons. Both structures are made of multiple substances, including tangles of alpha-synuclein fibrils. They are found in the substantia nigra and in other parts of the brain.

Protein molecules have a distinct and complex shape, which is required in order for them to do their jobs. The alpha-synuclein molecules in the brain of a Parkinson's disease patient are misfolded as well as tangled. The misfolded strands have the ability to cause nearby strands of alpha-synuclein with a normal structure to misfold. The protein is said to have prion-like propagation. A prion is a misfolded piece of protein that causes other proteins to misfold and produces some serious diseases, including Creutzfeldt-Jakob disease or CJD.

Lewy bodies and neurites in the substantia nigra

Lewy bodies and neurites in the substantia nigra

The normal function of alpha-synuclein in the body is unknown. It has been found around synaptic vesicles, which are involving in transmitting the nerve impulse between neurons. The vesicles release neurotransmitter molecules, which stimulate the next neuron. Alpha-synuclein may therefore have something to do with neurotransmission.

A synapse is the region where one neuron ends and another begins.

A synapse is the region where one neuron ends and another begins.

Constipation Before Parkinson's Disease

Some people experience constipation along with movement problems in Parkinson's disease. When some British researchers analyzed published reports, however, they discovered that a significant number of people mentioned in the studies experienced constipation before the muscle problems of Parkinson's appeared. The researchers also discovered that the constipation sometimes began more than a decade before the Parkinson's symptoms. (The constipation was an ongoing problem and not the occasional condition that healthy people might experience.) The early constipation may be caused by a different factor from the constipation that develops later.

The researchers examined the results of nine studies involving a total of 741,593 people. The pooled OR (odds ratio) of someone with constipation later developing Parkinson's disease was 2.27 compared to those without constipation. An OR of greater than 1 is significant. When the researchers restricted their analysis to constipation more than a decade before the first muscle problems, the pooled OR was 2.13. It's important to note that the results indicate an association and not necessarily a causal relationship. Nevertheless, they do suggest that a problem in the large intestine (where feces is produced) might be related to the development of Parkinson's disease.

The yellow fibres are part of the enteric nervous system around the digestive tract.

The yellow fibres are part of the enteric nervous system around the digestive tract.

The digestive tract is also known as the gastrointestinal tract, the GI tract, the alimentary canal, and the gut. The stomach, small intestine, and large intestine are major parts of the digestive tract.

Alpha-Synuclein in the Intestinal Nerves

The intestine is surrounded by a network of nerves that travel through the intestinal wall and make up the enteric nervous system. The system is sometimes referred to as a "second brain". Some Parkinson's patients have been found to have alpha-synuclein in both their enteric nervous system and their brain. The vagus nerve connects the enteric nervous system to the brain.

In 2014, a multinational team of researchers created a mixture of various types of human alpha-synuclein, some of which came from Parkinson's patients. They injected the mixture into the gut wall of rats. They found that the protein entered the vagus nerve and travelled up the nerve to the brainstem. The scientists say that this is the first experimental evidence that different forms of alpha-synuclein can travel from the gut to the brain (at least in rats).

Alpha-Synuclein and Gut Inflammation

One fact that puzzles researchers is why alpha-synuclein collects in the nerves around the gut. In 2017, a US research team found that protein had collected in the enteric nervous system of children who were experiencing gut inflammation as a result of various conditions, including an infection by norovirus. They also discovered that the amount of the protein in the nerves correlated with the severity of the inflammation in the gut.

In lab equipment, the alpha-synuclein attracted cells from the immune system, including neutrophils and monocytes (types of white blood cells). The researchers believe that the protein produced the intestinal inflammation as part of an immune response instead of the inflammation triggering the appearance of the protein. Inflammation is often a helpful process for repairing injuries and getting rid of pathogens, but not if it's excessive.

The scientists propose that alpha-synuclein production in the gut is a normal activity in the immune system that becomes out of control in Parkinson's disease. Specific pathogens in the gut may trigger an excessive production of alpha-synuclein with abnormal properties, especially if infections are severe and repeated or if they are chronic.

According to the researchers, one chronic infection that may trigger abnormal alpha-synuclein production is caused by the bacterium named Helicobacter pylori. The researchers say that there is an association between a chronic H. pylori infection in the gut and an increased risk of PD. H.pylori is the bacterium that produces peptic ulcers. A vagotomy (removal of part of the vagus nerve) is sometimes used to treat the ulcers. Patients who receive this treatment have a decreased risk of PD.

A Possible Effect of Another Gut Microbe

An interesting experiment with animals indicates that a protein made by specific gut bacteria can trigger alpha-synuclein deposits in both the intestine and the brain of rats. The protein is made by some Escherichia coli bacteria and is known as amyloid protein curli, or curli for short.

The animals involved in the experiment were elderly rats. After bacteria producing curli were placed in the gut of the animals, an increased amount of alpha-synuclein was found in the nerves of both the gut and the brain of the animals. In addition, researchers observed a change in behaviour of the glial cells in the central nervous system in response to the increased level of alpha-synuclein. Neither of these effects were produced when bacteria that couldn't produce curli were placed in the rats.

The olfactory bulb may play a role in Parkinson's disease.

The olfactory bulb may play a role in Parkinson's disease.

Role of the Olfactory Bulb

Although multiple researchers are exploring the role of the digestive tract in Parkinson's disease, some are paying attention to the olfactory bulb instead. The bulb is located at the base of the brain and in involved in the sense of smell.

Nerves and receptors extend from the bulb into the lining of the nasal cavity. The receptors send signals to the olfactory bulb, which then sends messages to other parts of the brain. People with PD may experience problems with their sense of smell years before movement problems appear.

Scientists at the Max Planck Research Unit for Neurogenics and the University of Auckland have discovered that people with Parkinson's have half the total volume of functional units (glomeruli) in their olfactory bulb compared to the situation in healthy people. In addition, the distribution of the functional units is different.

Some researchers say that Lewy bodies are found in the olfactory bulb before they are found in the substantia nigra (at least in the cases that they've studied). They suspect that a substance that enters the nose may cause or increase the risk of PD. These substances may include viruses, pesticides, and heavy metals.

Even if the pathology (of Parkinson's disease) is very much driven by brain abnormalities, it doesn't mean that the process starts in the brain.

— Michael Schlossmacher, Ottawa Hospital Research Institute, via Scientific American

Looking to the Future

The interactions between processes in the body and between the body and the environment are numerous and complex. The situation is becoming increasingly interesting as more discoveries are made. The often intricate web of activities that take place inside us and the genetic variations in humans can make understanding disease difficult, however. It's important that we understand the body so that we can treat disease.

Additional research projects besides the ones mentioned in this article support the idea of a link between the gut and Parkinson's disease. More details about the potential relationship are needed, however. Clarification of the circumstances under which alpha-synuclein is helpful (if it in fact is) and under which it's harmful are essential.

There may be multiple causes or sites of origin of Parkinson's disease and multiple processes in the body that can make the disease worse. Some researchers suspect that this variation is why different patients have different symptoms and different rates of disease progression.

It's important to note that it's not inevitable that people with problems mentioned in this article will develop PD at some point. Digestive and sensory problems usually have other explanations. Understanding the factors that control the disease and any links to body parts beyond the brain could be very useful with respect to improving its treatment, however.

References

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2018 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on June 28, 2020:

Thank you very much, Inspiredbro. I appreciate your visit and comment.

Inspiredbro on June 28, 2020:

Wonderful article, you are really good at biology.

Linda Crampton (author) from British Columbia, Canada on August 12, 2018:

Thank you very much, Tim. The digestive tract seems to have far more importance than simply being the place where food is digested. It's an interesting part of the body.

Tim Truzy from U.S.A. on August 12, 2018:

Thanks Linda for an interesting and well written article. I've read recently scientists are beginning to think many diseases may have origins in the digestive tract. Thanks for sharing important information on Parkinson Disease in a timely and relevant article.

Much respect,

Sincerely,

Tim

Linda Crampton (author) from British Columbia, Canada on July 10, 2018:

Thanks for commenting, Rajan. It’s interesting that the digestive tract appears to affect so many conditions. Other causes of disease mustn’t be overlooked and must be studied, but the intestine seems to be important with respect to health.

Rajan Singh Jolly from From Mumbai, presently in Jalandhar, INDIA. on July 10, 2018:

Very informative article. As naturopathy explains, the seat of all disease is the digestive tract, the colon to be precise. And the root cause is constipation caused due to a variety of reasons including wrong eating habits. So somewhere along the current thinking is correct.

Thank you for sharing.

Linda Crampton (author) from British Columbia, Canada on July 08, 2018:

Thank you very much for the comment, Pamela. It does sound like researchers are making headway. I hope new treatments are discovered as soon as possible to help those who currently have the disease.

Pamela Oglesby from Sunny Florida on July 08, 2018:

Linda, This article really explains so much about this complicated disease. It sounds like scientist have made headway about understanding the development of this disease. i hope they can find a way to treat this disease also. Excellent article!

Linda Crampton (author) from British Columbia, Canada on July 03, 2018:

I appreciate your visit and comment, Eileen. I'm hoping that better treatments appear in the near future.

Ethel Smith from Kingston-Upon-Hull on July 03, 2018:

Thanks for a very informative hub. We have to hope better treatments follow

Ann Carr from SW England on May 30, 2018:

Thank you, Linda.

Ann

Linda Crampton (author) from British Columbia, Canada on May 29, 2018:

Hi, Ann. I'm sorry that people close to you have or had Parkinson's disease. It's certainly a distressing condition. I hope new discoveries are able to help your partner's brother soon.

Ann Carr from SW England on May 29, 2018:

This is really interesting, Linda. My father had Parkinson's and so does my partner's brother. It is a distressing condition for all concerned.

I'm intrigued regarding the links with other functions of the body. The research into Parkinson's has so far to go but they seem to be getting more and more information to help those afflicted.

This is so detailed and well-researched. Thank you for setting it out so clearly.

Ann

Linda Crampton (author) from British Columbia, Canada on May 27, 2018:

I hope researchers come up with a solution, too, Nithya. Thanks for the visit.

Nithya Venkat from Dubai on May 27, 2018:

Never thought that the digestive tract could be involved in Parkinson’s disease. I hope they come up with a solution for this disease.

Linda Crampton (author) from British Columbia, Canada on May 25, 2018:

Hi, Leah. Yes, the gut seems to be important in a range of diseases. The latest discoveries are very interesting.

Leah Kennedy-Jangraw from Massachusetts on May 25, 2018:

It seems researchers are discovering more and more ways our gut is involved in disease. Very interesting read!

Linda Crampton (author) from British Columbia, Canada on May 25, 2018:

Hi, Dora. I appreciate your comment. The potential relationship between the disease and the digestive tract or the olfactory bulb is very interesting.

Dora Weithers from The Caribbean on May 25, 2018:

Interesting how a nerve disease could start with the digestive tract or the olfactory bulb. Your article gives very good information and explanations. Thank you.

Linda Crampton (author) from British Columbia, Canada on May 25, 2018:

Thank you, Chitrangada. Parkinson's disease is a sad disorder. I hope it doesn't stay that way and that we're soon able to deal with it better.

Chitrangada Sharan from New Delhi, India on May 25, 2018:

Great article, with very useful information shared by you, about Parkinson’s disease. This is scary and sad, for those who suffer from it, and in fact the entire family, to see their loved ones suffer.

I just wish that better and effective treatments are available soon. One of my older relatives had developed this condition, who was otherwise quite healthy and fit in his prime days. So sad!

Thanks for sharing your knowledge with the readers!

Linda Crampton (author) from British Columbia, Canada on May 23, 2018:

You’ve asked an interesting question, Bede. I did some exploration and found two studies that support the idea of depression preceding the motor symptoms of Parkinson's disease in some people. There is uncertainly about the reason for the link.

The patient may already have PD (even though motor symptoms haven’t yet appeared) and the depression is an early symptom of the disease. On the other hand, the brain changes that cause depression may later cause (or contribute to) the characteristic changes present in PD.

There seems to be a tangled web of information to explore in relation to Parkinson’s disease.

Bede from Minnesota on May 23, 2018:

Hi Linda, I’m back for another little visit. My question referred to depression as another possible cause, not effect, of Parkinson’s. In any case, your article is quite thought provoking. I need to reread some of it as it’s somewhat technical in parts.

Linda Crampton (author) from British Columbia, Canada on May 23, 2018:

I find the relationships fascinating as well. Heidi. The study of the human body is still revealing unexpected facts. Thanks for the comment.

Heidi Thorne from Chicago Area on May 23, 2018:

I find it so fascinating that often what we deem as completely unrelated issues could cause or impact other health disorders or conditions. And this is a big one! Definitely a reason to think more holistically about what ails us. Thanks, once more, for sharing your insight and knowledge on the natural world!

Linda Crampton (author) from British Columbia, Canada on May 23, 2018:

It is interesting. I hope new research clarifies the situation. I appreciate your comment very much, Manatita.

manatita44 from london on May 22, 2018:

Interesting article and right on que with the symptoms from a hospital point of view.

Mohammed Ali also received lots of punches to his stomach! Interesting, eh?

The body of ours is truly fascinating! Well done, Linda.

Linda Crampton (author) from British Columbia, Canada on May 22, 2018:

Thanks, Larry. The body is complex, but as you say, it's amazing, too!

Linda Crampton (author) from British Columbia, Canada on May 22, 2018:

Hi, Natalie. I'd never heard of the possible connection either until I read a recent news item about it. Once I started doing some research, I discovered how much evidence supported the idea. My article would have been a lot longer if I had described all the research supporting the connection. It will be very interesting to see what is discovered next and to see whether proof for the connection is found.

Larry W Fish from Raleigh on May 22, 2018:

An interesting article, Linda. I am always amazed when I read that a condition in one part of the body can lead to another disease or condition. The body really is an amazing, complex, thing.

Natalie Frank from Chicago, IL on May 22, 2018:

This is the first time I've heard of a possible connection between the digestive system and Parkinson's disease. One of my parent's best friends died from Parkinson's. It would be wonderful if this somehow lead to new possibilities for treatment or perhaps even prevention.

Linda Crampton (author) from British Columbia, Canada on May 22, 2018:

Hi, Bede. Thanks for the visit. Some people with Parkinson's disease do develop depression, but this isn't the case for everyone.

Bede from Minnesota on May 22, 2018:

There seems to be a correlation between depression, constipation, and dementia; is there a link between Parkinson’s disease and depression? Anyway, my own opinion is that the Parkinson’s disease starts in the brain and prolonged constipation is one of the first symptoms. Thanks Linda, for another informative article.

Linda Crampton (author) from British Columbia, Canada on May 22, 2018:

Thank you very much for the comment, Larry. The unexpected connections between different areas of the body are surprising and interesting.

Larry Rankin from Oklahoma on May 22, 2018:

It's amazing how the most unlikely body parts are connected.

Always interesting, friend.

Linda Crampton (author) from British Columbia, Canada on May 22, 2018:

Hi, Bill. The discoveries made by researchers are amazing. I hope new and significant discoveries continue to be reported. Thanks for the comment.

Bill De Giulio from Massachusetts on May 22, 2018:

Hi Linda. How interesting. It really is amazing how the body works. I never would have thought that PD could start in the gut, but it’s amazing what research is discovering. Hopefully the current research leads to breakthroughs in treating PD. Thanks for the education.

Linda Crampton (author) from British Columbia, Canada on May 22, 2018:

Thank you, RTalloni. I think the research is encouraging, too. I hope it leads to good things. Your last statement is very interesting. It's an excellent point!

RTalloni on May 22, 2018:

As always a neat read. Your practical explanations are always interesting and useful. Learning about the research going into Parkinsons is encouraging for any who do or may face the disease.

How little we really know about these amazing bodies we've been given continues to be a part of research as we delve into the intricacies of how they work. I've come to believe that one of the long-standing mistakes is the thought that what is the same about human bodies outweighs the differences in them.

Linda Crampton (author) from British Columbia, Canada on May 22, 2018:

It would be wonderful if we could cure it, Bill. It would be great if we could prevent it, too. It can sometimes be a very unpleasant disease.

Linda Crampton (author) from British Columbia, Canada on May 22, 2018:

Hi, Mary. The connections are very interesting. Understanding them is definitely crucial to our health. Thanks for the visit.

Bill Holland from Olympia, WA on May 22, 2018:

I had not heard this but it is fascinating. This is one ugly disease....wouldn't it be lovely if they could cure it?

Mary Norton from Ontario, Canada on May 22, 2018:

Research always brings new understanding. It is interesting to note how our body functions are so interconnected that taking care of the different parts is crucial to our health. Thank you for this information.

Linda Crampton (author) from British Columbia, Canada on May 21, 2018:

Thanks for commenting, Peggy. It's sad to discover how many people know someone with Parkinson's disease. I'm glad that lots of researchers are exploring the disorder.

Peggy Woods from Houston, Texas on May 21, 2018:

These findings are certainly interesting. We have an acquaintance that has Parkinson's Disease. It not only affects him but impacts his family as well. Hopefully with more research they will eventually find a cure or perhaps a way to prevent the disease from developing in the first place.

Linda Crampton (author) from British Columbia, Canada on May 21, 2018:

Hi, Patty. I'm sorry about your coach. One of my relatives had the disease in her later years. It was a sad situation for her. I hope that better treatments for everyone are available soon.

Patty Inglish MS from USA and Asgardia, the First Space Nation on May 21, 2018:

One of my former high school coaches, now 80 years old, unfortunately is in a nursing home with Parkinson's. It is sad and I will be happy when better treatments are available. This research you show us is hopeful.

Linda Crampton (author) from British Columbia, Canada on May 21, 2018:

That's a sad story, Flourish. I hope treatments for the disease improve rapidly.

FlourishAnyway from USA on May 21, 2018:

It’s interesting that the olfactory bulb is involved in this way. I’ve found that one person in the workplace who wore too much cologne was later diagnosed with PD. It was one hallmark that things weren’t working as intended.