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Changes in the gut microbiome may be an early indicator of Parkinson’s disease

Our resident nutritionist Magdalena Marvell returns with another information packed article on gut microbiome and how it could be an early indication of Parkinson’s disease.

Parkinson’s disease is a common condition that affects how the body moves. Recent research suggests that negative alteration of the microbial community in the gut (known as gut dysbiosis) may play a role in causing and worsening Parkinson’s disease (PD).

Studies have found changes in the types of bacteria present in the gut of people with PD, and animal studies have shown that gut dysbiosis can contribute to the development and progression of the disease in a number of ways. These include making the gut more permeable, increasing inflammation, causing abnormal protein buildup, increasing stress, and decreasing the production of important chemicals in the brain.

The bacteria in our gut, which is sometimes called the “second brain” or the “forgotten organ”, can affect how our brain works through a communication pathway called the microbiota-gut-brain axis. This communication can happen in both normal and abnormal conditions. With advances in scientific techniques, we now know that the gut bacteria plays an important role in regulating this communication between our gut and brain. In fact, the makeup of our gut bacteria is unique to each individual, like a personal identity card or fingerprint1.

Scientists are now starting to realise that the gut and brain are connected and communicate with each other through a pathway called the microbiota-gut-brain axis. Recent discoveries have shown that problems in the gut might play a role in causing and worsening PD2. This has opened up new possibilities for understanding the causes of PD and developing new treatments. Studies have found that the gut bacteria can affect the communication pathway between the gut and brain through different mechanisms such as hormones, immune system, and nerves. This supports the idea that the disease process in Parkinson’s might start in the gut and spread to the brain3.

People with PD commonly experience problems with their digestion, such as constipation, bloating, nausea, difficulty swallowing, excessive drooling, vomiting, and delayed stomach emptying. These digestive issues can start many years before the onset of movement problems, and may be seen in more than 80% of PD cases. Researchers have found that people with constipation have a higher risk of developing PD, and this symptom can appear more than a decade before diagnosis.

The digestive symptoms are linked to changes in a protein called α-synuclein, which is involved in the brain damage that causes PD. The buildup of α-synuclein is found not only in the digestive system of people with PD, but also in people who haven’t yet developed movement problems. This suggests that the disease process may start in the digestive system and spread to the brain through a nerve called the vagus nerve. This idea is supported by recent research and is now widely accepted. Gut bacteria may also play a role in the progression of PD.

Studies have found that there are changes in the gut bacteria of people with PD. Even the appendix, which is part of the digestive system, has shown differences in its bacteria. However, many external factors like age, sex, weight, race, location, diet, medications, and lifestyle can influence the structure and composition of the gut bacteria.

The balance of good and bad
The balance of good and bad bacteria in our gut, known as gut microbiota, plays an important role in our overall health. In PD, there are changes in the gut microbiota that have been shown to impact the development and progression of the disease. One such change is a decrease in bacteria that produce short-chain fatty acids (SCFAs).

SCFAs have been found to play an important role in communication between the gut and brain, and can help protect against damage to neurones in the brain that are affected in PD.

Microbial SCFAs have an important role in the communication pathway between the microbiota, gut, and brain by regulating the gut epithelial barrier and blood-brain barrier integrity, inflammatory processes, and endocrine signalling. A decrease in SCFAs-producing bacteria may lead to harmful effects in PD patients such as gut problems, increased inflammation, and higher risk of abnormal protein deposition in the gut and brain.

Recent studies suggest that SCFAs can protect against PD by promoting the survival of dopamine-producing cells in the brain. This suggests that changes in SCFAs may contribute to the development of PD, and increasing SCFAs levels could help slow the progression of the disease4.

In addition to SCFAs, there is evidence that changes in gut microbiota can also affect lipid metabolism, specifically the production of bile acids5. Certain bile acids, such as deoxycholic acid and lithocholic acid, have been found to be increased in PD patients and can lead to the accumulation of proteins that are associated with PD in both the gut and the brain. However, there are other bile acids, such as tauroursodeoxycholic acid and ursodeoxycholic acid, that have been found to be protective against damage to neurones and are being tested in clinical trials for their potential to treat PD.

Overall, the balance of bacteria in our gut can impact the development and progression of PD, and understanding these changes may lead to new avenues for earlier diagnosis and better treatments for the disease.

Patients with PD may experience “leaky gut,” a condition where the intestines become more permeable and allow unwanted substances to enter the body. The gastrointestinal (GI) tract is believed to be where the disease first starts. When there is an imbalance in gut bacteria, the protective lining of the intestines can break down, allowing harmful substances to enter the body.

This breakdown is associated with oxidative stress and increased exposure to endotoxins. These substances can then cause the abnormal accumulation of α-synuclein, a protein involved in the development of PD, in the enteric neurones. Markers of increased intestinal permeability have been found in the feces of PD patients, indicating that the disease affects the GI tract6.

Researchers have tried various methods to reduce the negative effects of gut dysbiosis and slow down the progression of PD. These methods include taking probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, undergoing fecal microbiota transplantation (FMT), making dietary changes, and using Chinese medicines7/8.

Many studies suggest that what we eat can impact the risk of developing neurodegenerative diseases like Parkinson’s. The type and amount of carbohydrates, proteins, and fats we eat, as well as our intake of fruits, vegetables, and omega-3 fatty acids, can all have an effect on our brain health. Eating a healthy diet pattern, such as the Mediterranean diet, may also have a neuroprotective effect on Parkinson’s.

The food we eat can have a direct or indirect effect on our health in different ways. Recent studies suggest that the impact of diet on our brain health is not due to a diet-induced inflammatory response, but rather because of how the food we eat affects the bacteria in our gut.

Eating a healthy diet, like the Mediterranean diet, can increase helpful gut bacteria and reduce gut problems associated with PD, which in turn can help to alleviate symptoms of PD. Foods like high-fiber fruits and vegetables, and complex carbohydrates in the Mediterranean diet can be broken down by the gut bacteria into metabolites called SCFAs, which can have a positive effect on PD. These metabolites can increase the activity of the nerves in our gut, helping to improve gut function and reduce PD symptoms.

The ketogenic diet, which is low in carbohydrates and high in fat with a moderate amount of protein, is being studied as a possible treatment for PD. Studies in rats have shown that the diet can improve their movement. The ketogenic diet can change the types of microbes living in the gut, increasing certain beneficial ones and decreasing others.

This change in the gut microbiome can result in less inflammation in the gut, which could be helpful in PD. However, no studies have looked at the effects of the ketogenic diet on the gut microbiome of people with PD.

Fasting or following a specific type of diet that mimics fasting may protect against PD by increasing certain hormone levels. These diets may also change the composition of gut bacteria, which can have beneficial effects.

Researchers have found that restricting calories can slow changes in gut bacteria that are associated with ageing, and this may improve stroke recovery9/10. However, studies have not yet explored the effects of these diets on gut bacteria in PD patients.

References:
1. pubmed.ncbi.nlm.nih.gov/31753762
2. pubmed.ncbi.nlm.nih.gov/33459114
3. pubmed.ncbi.nlm.nih.gov/34500451
4. pubmed.ncbi.nlm.nih.gov/31745471
5. pubmed.ncbi.nlm.nih.gov/29018272
6. pubmed.ncbi.nlm.nih.gov/22343151
7. pubmed.ncbi.nlm.nih.gov/23759244
8. pubmed.ncbi.nlm.nih.gov/35182833
9. pubmed.ncbi.nlm.nih.gov/26961958
10. pubmed.ncbi.nlm.nih.gov/21902666

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