27th of February 2019

Previously:

Many Parkinson’s patients appear to be plagued by gastrointestinal problems such as pain and constipation years before the official diagnosis. Me too. With the question: “Would it be possible to break the vicious circle called Parkinson’s in stomach and intestines?”, I visited the gastroenterologist in part 1 of ‘A Parkinsonian gastro-intestinal tract’ . In part 2, I pay a visit to Prof. dr. Aletta Kraneveld. She is Professor of Pharmacology at Utrecht University (the Netherlands) and wants to contribute as a scientist to the quality of life of people with a chronic disease. She is particularly interested in the role of the inhabitants of our intestines on our immune system and the health of our brain.

Our intestines as mirror of brain health

“More and more is known about the importance of good intestinal health for the functioning of the brain,” Kraneveld starts. “Studies in the laboratory – for example in the Petri dish or in animal models – show that there is a relationship between the composition of intestinal bacteria and the occurence of disorders such as autism, Alzheimer’s, depression and Parkinson’s disease” (1, 2).

Well before the interview, the research group of prof. dr. Aletta Kraneveld arouses my interest with their research into dietary interventions in mice with Parkinson’s disease (3, 4). The mice got Parkinson’s by administering the toxic substance rotenone. Rotenone is a pesticide that is known to increase the risk of Parkinson’s (5).

The mice, which received rotenone, did not only show motor symptoms, but also showed changes in their intestines. The composition of their intestinal bacteria changed, they showed symptoms of a leaky gut and they had higher inflammatory profiles than healthy mice.

The researchers investigated whether a diet could reduce the symptoms of the sick mice. In addition to prebiotic fibers – which promote the growth of certain intestinal bacteria – the mice also received precursor and auxiliary substances for the production of phospholipids. Phospholipids are important building blocks for our neurons. If the Parkinson’s mice consumed this diet, not only did their motor complaints diminish, but also the inflammation in their intestines decreased.

The question that offers hope is:

Can we influence the symptoms or maybe even alter the course of Parkinson’s disease with dietary interventions?

Prof. dr. Aletta Kraneveld

Of mice and men

For Kraneveld and her colleagues, the challenge is to translate results from animal models to human use. And that’s not simple at all. Kraneveld: “The precise link with the intestines is still unknown. There are indeed strong associations between the composition of the intestinal flora and the occurence of brain diseases such as Parkinson’s disease, but we do not yet know whether the connections are causal. A lot of research is still needed for this”.

Another complicating factor is that Parkinson’s isn’t a single disease. Several subtypes of the disease may react differently to the same treatment. The way we are currently investigating whether a new drug works does not help in speeding up discovery. Kraneveld: “In randomized, double-blind clinical trials, averages are taken from large groups of patients. The treatment is compared with a placebo, an agent with no active ingredients. If you average all information, the treatment often shows no significant effect and at the moment the entire study is then trashed, while it may well be that a limited group of patients have benefited during treatment. That’s a shame”.

Without conclusive evidence, the neurologist continues to revert to levodopa, which has been regarded as the holy grail since 1967 in combating the symptoms of Parkinson’s disease (6). But levodopa mainly affects the motor effects of Parkinson’s. Other symptoms – such as those in the gastrointestinal tract – do not benefit from taking levodopa.

Life style interventions as medicine

Kraneveld sees a way out: “That little has been proven does not mean that you can not do anything! As a person with a diagnosis you can experiment with lifestyle interventions yourself”. For example, a large-scale study will soon be launched in the Netherlands that is called “My own research” (Dutch). The project connects patients’ desire for control with a method that allows for scientific conclusions to be drawn.

In this study 500 people with chronic fatigue and a gut problem are recruited. The research starts with the measurement of inflammatory values ​​in their saliva, blood and poo. Then the participants choose a dietary intervention, such as a preparation that improves the firmness of the intestines or probiotics (micro-organisms such as bacteria or yeasts that we assume improve gut health). After 8 weeks, the research team takes a closer look at the inflammatory values ​​and complaints. The study doesn’t only look at the effect for all individuals in the study, but will also try to determine whether something can be said about the effects for certain groups.

In the meantime, the doctors of the future are also getting ready for lifestyle interventions. Kraneveld: “It’s the students themselves who wonder why they never hear anything about the role of nutrition and lifestyle in their education”. The Stichting Student en Voeding (Dutch) is composed of medicine students who organise extracurricular courses. They challenge future doctors to bring nutrition and lifestyle back as a medicine in the consulting room.

Human immune fitness

Kraneveld would like nothing more than to design a ‘human immune fitness lab’. It is her ultimate dream: “The human body is an integrated whole with the environment and our immune system plays an important role in this. At the moment, science and healthcare are still too much split into separate boxes. We have to practice system thinking, especially in complex diseases such as Parkinson’s disease. In a human immune fitness lab the resilience of our immune system could be investigated from many angles”.

As far as Kraneveld is concerned, patients will also be given an important place in this lab. According to Kraneveld, they are in the position to ask the very best questions scientists and healthcare practitioners.

Meanwhile in the hospital

Patients with Parkinson’s disease do not yet see much of Kraneveld’s dream in the examination room. For the time being, a visit to the hospital is dominated by investigating complaints and prescribing appropriate medication. Which is important, but it’s not everything. Dietary interventions are not the subject of discussion yet. And I personally feel that this should be the case. Not only in the future, but now.

The approach of My own research (Dutch) gives hope for a more personal healthcare where the patient has more control than currently is the case. Because, make no mistake. After all, people also want to do something themselves to increase their sense of control in an uncertain situation. Most of my fellow patients are already carrying out their own experiments as I write. And I myself got rid of my stomach pain through a diet experiment.

At present, no scientific conclusions are drawn from this kind of brave self-care attempts. If people will experiment with uncertain outcomes anyway, I think they should better do so according to a scientific method. In this way self-chosen experiments may contribute to the health of generations to come.

Your turn ..

What would improve your quality of life as a Parkinson’s patient?
What question isn’t asked in the hospital that should be asked?
What should science and care be paying attention to first?
Let me know in the comments or send an e-mail to sparks@verbeeldingskr8.nl.

Sparks  

Sources

(1) Bienenstock, J., Kunze, W. , Forsythe, P. (2015). Microbiotica and the gut-brain axis. Nutrition Reviews, Volume 73, Issue suppl_1, 1, Pages 28–31. Retrieved from https://doi.org/10.1093/nutrit/nuv019.

(2) Dinan, T.G., Cyran, J.F. (2017). Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. The Journal of Physiology, Volume 595, Issue2, Pages 489-503. Retrieved from https://doi.org/10.1113/JP273106

(3) Paula Pérez Pardo. Targeting the Gut-Brain axis in Parkinson’s disease. (2017). [THESIS]. Retrieved from https://dspace.library.uu.nl/bitstream/handle/1874/354242/Perez_Pardo.pdf?sequence=1&isAllowed=y 

(4) Perez-Pardo, P., Kliest, T., Dodya, H.B., Broersen, L.M., Garssen, J., Keshavarzian, A., Kraneveld, A.D. (2017) The gut-brain axis in Parkinson’s disease: Possibilities for food-based therapies. European Journal of Pharmacology, 817, (pp. 86-95). Retrieved from https://doi.org/10.1016/j.ejphar.2017.05.042

(5) Cao, F,. Souders, C.L. II, Perez-Rodriguez, V., Martyniuk, C.J. (2019). Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson’s Disease: A Focus on Chemicals of Epidemiological Relevance. Frontiers in Genetics, 9: 701. Retrieved from https://doi.org/10.3389/fgene.2018.00701

(6) Hornykiewicz, O. (2010). A brief history of levodopa. Journal of Neurology, 257(Suppl 2): 249. https://doi.org/10.1007/s00415-010-5741-y