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| This tissue section, taken from the intestine of a mouse unable to produce the neuropeptide VIP, clearly shows the striking frequency with which certain cell types occur on the intestine's surface. These include villous cells (red), mucus-producing goblet cells (yellow), Paneth cells (pink) and stem cells (green). Image Credit: © Charité | Luisa Barleben |
The intestinal nervous system, often referred to as the "gut brain", is essential in controlling digestion and maintaining the intestinal barrier. This protective layer, made up of the intestinal mucosa, immune cells and the microbiome, shields the body from the contents of the gut. Its effectiveness depends on the delicate balance among these components. If this balance is disrupted, inflammation, allergies, or chronic intestinal diseases can arise. The intestinal mucosa serves as the body’s primary defense against pathogens. While previous studies have shown that the intestinal nervous system is involved in immune responses in addition to digestion, its role in the development of intestinal epithelial cells has remained largely unclear until now.
An international research team led by the University of Bern, Inselspital Bern, Bern University Hospital and Charité, has now shown for the first time that the intestinal nervous system acts as a central regulator of the intestinal barrier. By releasing a specific molecule, it directs the development of different cell types in the intestinal wall and in this way shapes immune responses in the intestine that can promote allergies. The results of this study were recently published in Nature Immunology.
The intestinal nervous system as a "conductor" between stem cells and immune cells
In their study, the researchers investigated in the mouse model how specific nerve cells in the gut interact with intestinal stem cells. They focused on the vasoactive intestinal peptide (VIP), a messenger molecule produced by the intestinal nervous system. The findings show for the first time that intestinal nerve cells use VIP to communicate directly with intestinal stem cells, ensuring that these cells do not multiply too rapidly nor develop excessively into certain cell types. When this regulatory mechanism breaks down and VIP is absent, an excess of so-called tuft cells occurs. These cells then release signals that activate an allergy-like response in the intestine.
"Our findings show that the intestinal nervous system is a decisive factor in preserving a healthy intestinal mucosa, regulating immune responses, and ultimately maintaining an intact intestinal barrier," explains Dr. Manuel Jakob from the Department of Visceral Surgery and Medicine at Inselspital, research associate at the Department for BioMedical Research (DBMR) at the University of Bern and scientist at Charité. The study’s first author adds: "Our 'gut brain' is far more than a facilitator of digestion. It acts as a central hub for health, immunity, and potentially for conditions that affect large parts of the population. Interestingly, the results suggest that the effect may be shaped by the diet, i.e. the formulation of the food”.
New approaches for inflammatory and allergic gut diseases
A healthy gut microbiome and a balanced immune response are vital for protecting the body from disease, making research on the intestinal nervous system increasingly significant. "The mechanism we have uncovered may help explain why some individuals are particularly sensitive in the gut and how we might intervene more precisely in the future," explains Prof. Christoph Klose, head of the Neuroimmune Interaction research group at Charité's Institute of Microbiology, Infectious Diseases and Immunology and senior author of the study. "By deepening our understanding of how nerves, cells and immune responses interact in the gut, we can develop more targeted and personalized therapies - for example for allergies, irritable bowel syndrome or chronic inflammatory bowel diseases." The findings also suggest that these reactions might be directly influenced through diet. As a next step, the team plans to investigate how nutrition can be strategically used to support the nerve-gut axis and support intestinal health.
Research material: What Is: The Human Microbiome
Published in journal: Nature Immunology
Authors: Manuel O. Jakob, Nele Sterczyk, Sotiria Boulekou, Patrycja M. Forster, Luisa Barleben, Nadra Alzain, Katja J. Jarick, Roksana M. Pirzgalska, Bruno Raposo, Karl Hansson, Elisabeth E. L. Nyström, Aurelia Gondrand, Miguel González-Acera, Pierre S. Leclère, Marlen S. Lapson, Sarah Poggenseier, Divija Deshpande, Laura Velleman, Tilman Breiderhoff, Max Felix Brunkhorst, Anton M. Schüle, Gabriela M. Guerra, Pawel Durek, Mir-Farzin Mashreghi, Anja A. Kühl, Coco Chu, Christoph Schneider, Carl Weidinger, Britta Siegmund, Thierry M. Nordmann, David Voehringer, Jay V. Patankar, Christoph Becker, George M. H. Birchenough, Henrique Veiga-Fernandes, Francesca Ronchi, Marina Kolesnichenko, Andreas Diefenbach, and Christoph S. N. Klose
Source/Credit: University of Bern
Reference Number: imgy112525_01