More than a gut feeling: The brain-gut connection

What role does our digestive tract play in triggering Parkinson’s, multiple sclerosis or Alzheimer’s? Beate Winner is the speaker for a clinical research group exploring this question.

It is approximately six meters long. It is home to huge quantities of bacteria, viruses and fungi, totaling roughly ten times more than the number of cells we have in our body. And it may have a decisive influence on whether we fall ill with Parkinson’s, multiple sclerosis or dementia over the course of our lives.

We are talking about the gut. For a long time, medicine only cared about its decisive role in digestion. In recent years, however, it has become the focus of research for a quite different reason. “We have reason to suspect that a number of neurodegenerative diseases, diseases in which the nerve cells in the brain are damaged or destroyed, begin in the gut,” Beate Winner explains. “They only spread to the brain in the second step.”

Transport pathways to the brain

The Professor of stem cell models for rare neural diseases is the speaker of the clinical research group KFO 5024, which investigates these connections. Prof. Dr. Claudia Günther, Professorship for Gastrointestinal Pathophysiology at FAU, is responsible for scientific coordination. Interdisciplinary tandems of neuroscientists and gastroenterologists work together in the KFO with the aim of unraveling how the digestive tract exerts its influence over the gray cells. There are a number of potential communication channels. It is known that certain bacteria can trigger inflammation in the gut. The messenger substances in the immune system that are released as a result may travel to the brain via the bloodstream and presumably trigger inflammatory reactions in our brain. “Nowadays, it is believed that this process may contribute to the onset of multiple sclerosis,” says Winner.

For diseases such as Parkinson’s, another channel may play a role: the vagus nerve. Clusters of a protein known as alpha synuclein are found in certain regions of the brain in Parkinson’s patients, in particular in those responsible for movement. It forms clumps in nerve cells and damages them. “Interestingly, the same protein is often found in the digestive system of people with chronic inflammatory bowel diseases,” explains the FAU scientist. “These patients have a higher risk of developing Parkinson’s disease.”

It is possible that alpha synuclein is initially created in connection with a chronic inflammatory bowel disease, before moving from there to the brain and triggering Parkinson’s disease. The intriguing question is how the protein gets there. The vagus nerve, that links the brain to the digestive tract, is one possible candidate. Nerve fibers do not only transfer electrical impulses, they also act as a type of railway line that the body can use to transport molecules over long distances. “That is, however, only one of the options that are being discussed at the current time,” says Winner. It is also possible that the alpha synuclein is packed into little membrane-bound vesicles known as exosomes, that then reach the brain via the bloodstream.”

The working groups led by Prof. Dr. Jürgen Winkler (molecular neurology) and Prof. Dr. Stephan Wirtz and Prof. Dr. Raja Atreya (gastroenterology) are currently conducting a clinical study on these questions. The researchers hope to gain a new understanding of the role played by the “dispatching” of the alpha synuclein from the digestive tract into the brain in the triggering of the disease. “We also want to understand better how inflammatory changes in the gut can make nerve cells become ill. Our hope is that in future we may be able to treat this neurodegenerative disease before it damages the brain,” Winter emphasizes.

Research into inflammation with stem cells

Nowadays, excellent treatments are already available for treating chronic inflammatory bowel diseases such as Morbus Crohn. However, their success varies from patient to patient. Their success also only becomes apparent after some time has passed. KFO 5024 is therefore also investigating new methods aimed at allowing physicians to determine earlier whether the inflammation in the gut is receding or not.

Parallel to these studies on patients, the scientists are also conducting laboratory experiments with human cell cultures, using cell clusters generated from stem cells. These can be used, for example, to study how the function of the intestinal wall changes with chronic inflammation and which molecules are released as a result. Winner and her working group are able to cultivate such tissue for example from skin cells taken from patients. “We re-program this starting material and create exactly the tissue that we would like to investigate,” she explains.

Only relatively little is known about the influence of the digestive tract on the brain at the current time. Winter, who is originally from Straubing, believes that this will change in the coming years. One thing is clear from the findings so far: “Keeping your gut healthy and having a positive influence on the intestinal flora, i.e. the composition of bacteria and fungi in the gut, by eating a diet rich in fiber and probiotics is certainly not a bad idea.”

Prof. Dr. Beate Winner is a neurologist and neuroscientist, whose research focuses predominantly on neurodegeneration. After completing her specialty training in neurology and specializing in neurodegenerative diseases, she was awarded a Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation, and worked in Fred H. Gage’s laboratory at Salk Institute, La Jolla, USA. Since 2017, Winner has been the head of the Department of Stem Cell Biology, and she is the speaker of the Center for Rare Diseases Erlangen.

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Author: Frank Luerweg

This article is part of the FAU magazine

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