Prof. Sven van IJzendoorn, a cell biologist, and Dr. Hermie Harmsen, a microbiologist, both work at the University Medical Center Groningen (UMCG). They have jointly developed a unique model of the human gut in which they investigate exactly what happens when the gut flora changes. Prof. Sven van IJzendoorn shares his findings in this article.
The beneficial bacteria in our gut flora secrete short-chain fatty acids, among other things, substances that keep the intestinal wall in good condition. If you have fewer of these types of bacteria, the intestinal wall becomes less robust, and substances from "bad" bacteria can leak through it more easily. This causes alpha-synuclein, a protein found in nerve cells in the brain and the rest of the nervous system, to accumulate in the nerve cells in the gut. The idea is that these clumps travel to the brain over the years via the vagus nerve, a long nerve that runs through the body. We think that in half of people with Parkinson's disease, the disease begins in the gut and not in the brain.
Scientists agree that certain bacteria considered beneficial are less common in the intestines of people with Parkinson's disease. And that bacteria known to cause problems are more prevalent. However, there is considerable variation. It's impossible to predict which disease a person has based on a single gut flora. Furthermore, gut flora varies from person to person and also within the same person over time.
That's what this project is about. For the first time, we're using a human model to investigate whether the gut flora of someone with Parkinson's disease can alter the permeability of the intestinal wall and lead to changes in nerve cells. We've developed mini-intestines, also known as organoids, for this purpose.
This research is funded by ParkinsonNederland (a € 193.750,- grant was awarded at the end of 2025). Read more (in Dutch) here.
A kidney cell is a kidney cell because it runs the genetic program for kidney cells, while a blood cell runs the genetic program for blood cells. In the lab, we can erase that program and activate a different one. We've taken blood cells from people with Parkinson's disease and turned off the blood cell program and turned on the intestinal cell program. This way, we create intestinal tissue from a few cells. We're one of the few in the world to have integrated these intestinal cells with nerve cells, creating a true mini-gut. In this model, we combine the human intestine with the intestinal flora of people with Parkinson's disease.
We hope to answer two questions: can the intestinal flora of people with Parkinson's disease cause negative effects in the mini-gut of those same patients, and is that effect present in different versions of the intestinal flora? If the intestinal flora of one patient causes changes and that of another doesn't, you can examine the difference and determine which components of the intestinal flora are clinically relevant. This is important because it's much easier to intervene in the intestines than in the brain.
Within the UMCG, researchers from various disciplines collaborate. We get to know each other through meetings and lectures. That's how I met Hermie. It's the collaboration with Hermie and neurologist Professor Teus van Laar that makes this project possible. I'm a cell biologist interested in the intestines. For me, as a non-brain scientist, this project is a great entry point into Parkinson's disease. I find it fascinating because I study how effects in the intestines have consequences for the rest of the body. However, I can't culture bacteria or analyze gut flora. Hermie is a microbiologist interested in gut flora, but he can't create mini-intestines. So, we each have our own expertise. Without the infrastructure to bring together bacteria and mini-intestines and the collaboration between Hermie and myself, this research wouldn't have been possible.
