Researchers from Groningen University, The Netherlands discovered that bacteria from our gut can metabolize and block the action of the main drug used to treat Parkinson’s disease [1].

Parkinson’s disease is related to low levels of dopamine in the brain and the main treatment for the patients is levodopa (L-dopa), a precursor of dopamine. The drug is absorbed in the small intestine and through the bloodstream is transported to the brain, where it is converted into dopamine.

Prior studies showed that only part of the drug reaches the brain. This is because the human enzyme tyrosine decarboxylase (TDC) converts L-dopa to dopamine before it can get to the brain. Dopamine is too big to cross the strict barrier between the blood and the brain (while L-dopa can cross this barrier), so when this happens the drug can’t reach the brain regions that it needs to reach to treat Parkinson’s disease.

To avoid this early conversion of L-dopa to dopamine, patients receive L-dopa in combination with another drug, Carbidopa, which inhibits the activity of the human TDC enzyme. However, even with the combined treatment, L-dopa efficacy varies greatly between patients, meaning that for some patients the drug works well but for others, it doesn’t.

Since it was known that some bacteria have also TDC enzymes, researchers from Groningen University tried to answer whether these enzymes are present also in the gut bacterial communities and if yes, what is their implication with L-dopa treatment. For the first time, researcher El Aidy and her team discovered that some bacteria from the small intestine of the rats had TDC enzymes and were able to convert L-Dopa into dopamine similarly to the human TDC [1].

Furthermore, rats that had a lot of bacterial TDC in the small intestines also had less L-dopa and more dopamine in the bloodstream. This suggests that bacterial TDC is converting L-dopa to dopamine in the gut before it reaches the brain.

The next step was to test the effect of drugs, known to be effective against human TDC such as Carbidopa, against bacterial TDC. Carbidopa was highly effective in blocking the action of the human TDC (as we already knew), but it had minimal effect on the bacterial enzymes. This can explain why the effect of the drug differs between patients, even when they are given Carbidopa. It all depends on how much bacterial TDC a person has in his or her intestines.

To confirm these findings, researchers used also human fecal samples from patients with Parkinson’s disease. Indeed, results were in accordance with the animal studies: patients with high bacterial TDC in their gut were the ones who required higher dosages of L-dopa.

The human gut is colonized by a wide diversity of micro-organisms, and the more we learn about these bacteria, the more it becomes clear that it is very important to our overall health. However, even though our knowledge the gut bacteria increased rapidly the past decade, little still is known about their effect on drug metabolism. This seminal study, for the first time, describes how gut bacteria affect drug availability in patients with Parkinson’s disease and explains why some people require a higher dosage of L-dopa for the treatment to be effective. The next step is to find a way to also limit the effect of bacterial TDC on L-dopa and allow the drug to work as intended.

REFERENCES:
[1] van Kessel, Sebastiaan P., et al. “Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease.” Nature communications 10.1 (2019): 1-11.

Please share and like us:

Recently, I participated in the Radboud Talks 2019, a scientific pitch competition, where I was lucky to be one of the eight finalists.

Why Radboud Talks? It is a perfect opportunity to share my work/ideas with the world and to gain more experience regarding presentation skills. They organized two workshops beforehand, where I had the opportunity to learn presentation techniques from professionals (actors and science communication advisors). We also received a lot of feedback, so I really learned a lot about how to present my scientific work to a general audience.

Below you can find the video from the preliminaries based on which I was chosen as a finalist. There you can hear about my research project which is about gut bacteria and their potential role in ADHD (Attention Deficit Hyperactivity Disorder). ADHD is a common worldwide neurodevelopmental disorder. Every person with ADHD has a unique combination of symptoms and challenges. Importantly, it has a significant social impact on patients’ lives, causing disruption at school, work and relationships. Despite its societal importance, progress in understanding disease biology has been slow.

 

The study of the human microbiome has become a very popular topic, because of their revealed importance in human physiology and health maintenance. Numerous studies have reported that gut bacteria may have an effect on our mental health. Some studies showed a potential role of gut bacteria in a psychiatric disorder like depression, autism or Parkinson (1). Above all, diet showed to have a profound effect of ADHD symptoms. This was earlier described in this blog: https://newbrainnutrition.com/investigating-the-effects-of-a-dietary-intervention-in-adhd-on-the-brain/ and we know that diet is one of the main factors influencing gut bacteria. Taking all together, I am curious (and investigating) if gut bacteria play a role in ADHD and if yes what kind of effect do they have on ADHD symptoms.

REFERENCES:
Bastiaanssen, T., Cowan, C., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2018). Making Sense of … the Microbiome in Psychiatry. The international journal of neuropsychopharmacology22(1), 37–52. doi:10.1093/ijnp/pyy067

 

Please share and like us:


Welcome to New Brain Nutrition. You can enjoy FREE Online Courses when you Log In or Join here.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 728018

New Brain Nutrition is a project and brand of Eat2BeNice, a consortium of 18 European University Hospitals throughout the continent.

Partners:
You may log in here to our Intranet website with your authorized user name and password.