A preamble for prebiotics

# # # # For a long time it has been known that the microorganisms in our intestinal system play an important role in our overall health and wellbeing.  Recently, researchers have been exploring how these tiny creatures and entities may be influencing Parkinson’s, and whether manipulation of them may impact the progression of the disease. In today’s post, we will review a new pilot clinical study that investigated the effects of a prebiotic fiber intervention in a group of people with Parkinson’s. # # # #

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Adam and Eve were not alone. Source: Metode

You should never feel alone, because you most definitely are not.

I do not wish to alarm you, but there is approximately 2kg (4.4 pounds) of microorganisms in your gut.

And to put that into context, the “microbiota” of the gut is actually heavier by weight than your brain (1.5kg – 3.3 pounds).

What does “the microbiota” mean?

The microbiota refers to microorganisms that colonise various defined parts of the body (such as our skin or gastrointestinal tract). The human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person. By mass, the microbiota of the human body make up about 1 to 3 percent of our overall weight (weighing approximately two to three kilograms in an adult – Source). Collectively, it is one of our heaviest organs.

And whether you like it or not, you definitely need these little passengers. They serve a wide variety of necessary functions.

Source: The conversation

The microorganisms in the human gut, for example, perform all manner of tasks for you to make your life easier. From helping to break down food, to aiding with the production of certain vitamins (in particular B and K) that you do not make yourself.

So, as I said, you are never alone. And please remember that you are responsible for more than just yourself.

And the microbiota should not be confused with the microbiome, which refers to the collection of different genomes (DNA) from all the microorganisms in these microbiota.

Source: Twitter

Ok, understood. What do they have do with Parkinson’s?

We have previously explored gut microbiota/microbiome research in Parkinson’s on this website (Click here, here, here and here for some examples).

It does appear evident that the activity of the gastrointestinal system could be having an important impact on Parkinson’s.

And what is interesting is that we now have researchers conducting clinical trials influencing the microbiota of the gut.

Can you give an example?

This report was recently published:

Title: An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson’s disease participants.
Authors: Hall DA, Voigt RM, Cantu-Jungles TM, Hamaker B, Engen PA, Shaikh M, Raeisi S, Green SJ, Naqib A, Forsyth CB, Chen T, Manfready R, Ouyang B, Rasmussen HE, Sedghi S, Goetz CG, Keshavarzian A.
Journal: Nat Commun. 2023 Feb 18;14(1):926.
PMID: 36801916                (This report is OPEN ACCESS if you would like to read it)

In this study, the researchers conducted an open-label, non-randomized study in which they evaluated the impact of a prebiotic intervention on 10 newly diagnosed, non-medicated people with Parkinson’s and 10 people with Parkinson’s who are already taking medication.

Interesting. But what is a prebiotic?

Another two important terms to differentiate before we get too far into this: prebiotic and probiotic.

Prebiotics are non-digestible fibres that act as food for microorganisms, promoting their growth and activity.

Probiotics on the other hand, are living microorganisms that, when consumed in adequate amounts, can provide health benefits.

Source: Eufic

Basically, prebiotics are the food source for our gut bacteria, while probiotics are the live bacteria that offer health benefits when consumed.

Got it. So what did the investigators find?

The researchers conducted a short 10-day, open-label, non-randomized study to determine if:

1. Daily consumption of the prebiotic mixture for 10 days is tolerable
2. Daily consumption of the prebiotic mixture was safe for use in PD patients
3. Daily consumption of the prebiotic mixture impacts PD-relevant biological outcomes

For the last objective, they did a deep dive analysing blood and fecal samples to assess changes in various biochemical measures (Click here to learn more about the details of this study).

What was the prebiotic treatment used in the study?

For the 10 days of intervention, the 20 participants consumed a snack bar (from BetterBiotics) composed of:

• 30% resistant starch (raw potato starch),
• 30% resistant maltodextrin (Nutriose^TM),
• 30% stabilized rice bran, and
• 10% agave branched inulin

These component were included to support the growth of a diverse group of beneficial bacterial groups and promote the production of three short chain fatty acids.

What are short chain fatty acids?

Short-chain fatty acids (SCFAs) are organic acids with one to six carbons, and they are produced by gut microbiota through fermentation of non-absorbable dietary fiber.

Source: Jitc.bmj

Acetic acid, propionic acid, and butyric acid are the most abundant SCFAs in the human gut.

After being produced and absorbed in the gut, SCFAs are transported to the liver, and some of them enter the systemic blood circulation system.

Why were the researchers trying to increase the levels of SCFAs?

People with Parkinson’s have been reported to have lower levels of certain SCFAs in their bodies.

This report here demonstrates this finding:

Title: Serum short-chain fatty acids and its correlation with motor and non-motor symptoms in Parkinson’s disease patients.
Authors: Wu G, Jiang Z, Pu Y, Chen S, Wang T, Wang Y, Xu X, Wang S, Jin M, Yao Y, Liu Y, Ke S, Liu S.
Journal: BMC Neurol. 2022 Jan 7;22(1):13.
PMID: 34996385              (This report is OPEN ACCESS if you would like to read it)

In this study, the researchers collected blood samples and clinical data from 50 individuals with PD and 50 unaffected, age-matched controls. The concentration of SCFAs in the blood (serum) was measured and they found that people with Parkinson’s were significantly deficient in certain SCFAs:

Source: PMC

Note in the graph above that two of the main SCFAs (propionic acid and butyric acid – the green bars are controls and the orange bars are PD cases) are significantly reduced in the blood of people with Parkinson’s. And when they looked at the clinical data, the investigators found that the changes in propionic acid levels is correlated with motor symptoms, cognitive ability and non-depressed state.

Other research groups have reported similar findings, such as:

Title: Bacterial Butyrate in Parkinson’s Disease Is Linked to Epigenetic Changes and Depressive Symptoms.
Authors: Xie A, Ensink E, Li P, Gordevičius J, Marshall LL, George S, Pospisilik JA, Aho VTE, Houser MC, Pereira PAB, Rudi K, Paulin L, Tansey MG, Auvinen P, Brundin P, Brundin L, Labrie V, Scheperjans F.
Journal: Mov Disord. 2022 Jun 20. Online ahead of print.
PMID: 35723531                 (This report is OPEN ACCESS if you would like to read it)

In this study, the researchers collected blood samples and clinical data from 55 people with Parkinson’s and 55 unaffected, age-matched controls, and found that “decreased levels of bacterially produced butyrate are related to epigenetic changes in leucocytes and neurons from PD patients and to the severity of their depressive symptoms.”

Epigenetics is the study of how non-genetic factors affect genetics (Click here to read a old SoPD post on this topic). The SCFAs butyrate has been reported to promote epigenetic remodeling of DNA (Click here to read an old review on this topic).

Long story short, SCFAs are reduced in people with Parkinson’s.

Got it. But why are SCFAs important?

SCFAs are believed to be critical in maintaining the integrity of the intestinal barrier. And when SCFAs are low, the intestinal wall becomes more ‘leaky’, meaning that more pro-inflammatory bacterial components are escaping the gut and entering circulation. These factors can put stress on cells in the body (particularly the brain) that may already be vulnerable (Click here and here for more reading on this topic).

Therefore, by increasing SCFAs, the gut becomes less ‘leaky’ and fewer gut derived pro-inflammatory factors are allowed to circulate.

Ok. So what did the researchers find in the prebiotic clinical study?

Well, first, they found that the prebiotic was well-tolerated and safe over the 10 days of treatment.

Second, similar to previously published studies, the investigators reported that the participants in their trial had reduced levels of SCFAs, which were elevated by the 10 day intervention in the participants with who were already being treated with dopaminergic medication (Total SCFAs in the blood went from 1.97 ug/mL at the start of the study to 3.22 ug/mL after 10 days of treatment).

The researcher reported that “Overall, the prebiotic intervention reduced the relative abundance of putative pro-inflammatory bacteria and increased the abundance of putative SCFA-producing bacteria”.

On the biochemical measures, the investigators reported some interesting changes, including a significant reduction in neurofilament light chain levels in the blood:

After just 10 days. Source: PMC

What are neurofilament light chains?

Neurofilament light chain (or NfL) is a protein that is currently being investigated as a biomarker of neuronal injury in various neurological conditions. NfL is a scaffolding protein that is found inside of cells, particularly within axons (the branches of neurons). So the assumption is, if there is increased levels of this protein in the blood then neurons must be degenerating in the brain.

Elevated levels of NfL have been found to be associated with Parkinson’s:

Title: Association of Neurofilament Light With the Development and Severity of Parkinson Disease.
Authors: Halloway S, Desai P, Beck T, Aggarwal N, Agarwal P, Evans D, Rajan KB; Chicago Health and Aging Project.
Journal: Neurology. 2022 May 31;98(22):e2185-e2193.
PMID: 35418452                  (This report is OPEN ACCESS if you would like to read it)

In this study, the researchers assessed NfL levels in 1,327 older participants from the Chicago Health and Aging Project (CHAP). They found that 77 of the participants had Parkinson’s and they also had a 2-fold higher concentration of NfL in their blood than the rest of the cohort. Curiously, when they looked back at old blood samples, the investigators found that the association was significant more than 5 years before diagnosis. They also reported that a higher concentration of NfL in the blood was associated with a faster rate of physical decline in the people with Parkinson’s..

And in the 10 day prebiotic study, the researchers found reductions in NfL levels?

Yes, and the result was particularly driven by newly diagnosed, non-medicated PD participants:

After just 10 days. Source: PMC

The prebiotic pilot study was very small and very short (20 people and only 10 days long). In addition, it was open label and there was no placebo control. Nevertheless, it provided some intriguing results. The researchers concluded that their “proof-of-concept study provides the scientific rationale for future studies evaluating the potential of a microbiota-directed prebiotic intervention as a disease-modifying therapeutic approach in PD patients“.

It will be interesting to see a larger, better controlled and longer study of this prebiotic in the near future.

So what does it all mean?

We contain multitudes, and the vast majority of the time we are blissfully unaware of them. The bacteria in our guts are silent passengers who can have a significant impact on our lives without us even realising. Some of them carry the ability to do harm, but equally, there are many that exhibit beneficial properties. Researchers have been exploring which are the ‘good’ bacteria, and investigating how to encourage their growth.

A new pilot study that investigated the providing of food for some of these ‘good’ bacteria has provided encouraging results in a small cohort of people with Parkinson’s after just a short period of treatment. The study provides justification for further assessment of this particular intervention, but also supports the broader field of research exploring the interaction between the gut and the brain. Hopefully this research will be fruitful as it would provide a quicker avenue of therapeutic intervention than the long wait for drug and surgerical procedures currently being developed.

We’ll be watching this space closely at the SoPD HQ.

 

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EDITOR’S NOTE: The author of this post is an employee of Cure Parkinson’s, so he might be a little bit biased in his views on research and clinical trials supported by the trust. That said, the trust has not requested the production of this post, and the author is sharing it simply because it may be of interest to the Parkinson’s community.

The information provided by the SoPD website is for information and educational purposes only. Under no circumstances should it ever be considered medical or actionable advice. It is provided by research scientists, not medical practitioners. Any actions taken – based on what has been read on the website – are the sole responsibility of the reader. Any actions being contemplated by readers should firstly be discussed with a qualified healthcare professional who is aware of your medical history. While some of the information discussed in this post may cause concern, please speak with your medical physician before attempting any change in an existing treatment regime.

In addition, many of the companies mentioned in this post are publicly traded companies. That said, the material presented on this page should under no circumstances be considered financial advice. Any actions taken by the reader based on reading this material is the sole responsibility of the reader. None of the companies have requested that this material be produced, nor has the author had any contact with any of the companies or associated parties. This post has been produced for educational purposes only.

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