Image: The enteric nervous system influences the composition of the intestinal barrier via the signalling molecule VIP. If VIP is absent, certain cell types are more prevalent on the intestinal surface, as this tissue section (mouse model) shows: tufted cells (red), mucus-producing goblet cells (yellow), Paneth granule cells (pink), and stem cells (green). © Charité | Luisa Barleben
Berlin, November 25, 2025
Joint press release from Charité and the University of Bern
An international study led by Charité – Universitätsmedizin Berlin and researchers from Bern has uncovered a previously unknown function of the enteric nervous system. As the team now describes in the journal Nature Immunology*, the enteric nervous system regulates the composition and stability of the intestinal barrier. If this protective mechanism is disrupted, a predisposition to allergies develops. The findings open up new perspectives for the treatment of allergies, chronic inflammatory bowel diseases, and irritable bowel syndrome.
The enteric nervous system, often referred to as the “gut brain,” plays a crucial role in regulating our digestion and maintaining the so-called intestinal barrier. This protective layer separates the body from the intestinal contents and consists of the intestinal mucosa, immune cells, and the microbiome. For the intestinal barrier to function effectively, all components must be in balance. If this balance is disrupted, inflammation, allergies, or chronic intestinal diseases can occur. The intestinal mucosa is considered the most important line of defense against pathogens. Previous studies had shown that the enteric nervous system, in addition to its role in digestion, also plays an important role in immune responses in the gut. However, the extent to which the enteric nervous system influences the development of intestinal cells has remained largely unexplored.
An international research team led by Charité, the University of Bern, and Inselspital Bern, University Hospital Bern, has now demonstrated for the first time that the enteric nervous system acts as a central switch for the intestinal barrier. Through a released messenger substance, it not only controls how cells of the intestinal wall develop into different cell types, but also influences the immune responses in the gut that promote allergies.
The enteric nervous system as a “conductor” between stem cells and immune cells
In their study, the researchers used a mouse model to investigate how specific nerve cells in the gut communicate with intestinal stem cells. They focused on the so-called vasoactive intestinal peptide (VIP), a messenger substance produced by the enteric nervous system. The study’s results show for the first time that enteric nerve cells communicate directly with intestinal stem cells via the VIP messenger. This ensures that the stem cells do not proliferate too quickly and do not mature too extensively into specific cell types. If this regulatory mechanism is disrupted and the VIP messenger is absent, an excess of so-called tufted cells develops. These cells then release signals that trigger a kind of allergy program in the gut.
“Our results demonstrate that the enteric nervous system is a crucial factor in maintaining a healthy intestinal mucosa, immune regulation, and ultimately, a healthy intestinal barrier,” explains Dr. Manuel Jakob from the University Clinic for 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 therefore much more than just a digestive aid. It’s a central switch for health, immunity, and potentially also diseases that affect a great many people. Interestingly, the results suggest that the effect is also influenced by the type of diet, i.e., the composition of the food.”
New Approaches to Inflammatory and Allergic Diseases of the Gut
A healthy gut microbiome and a stable immune response are essential for defending against diseases, which is why research into the enteric nervous system is of great relevance. “The discovered mechanism could explain why some people react hyper sensitively in the gut and how we can intervene in a targeted way in the future,” explains Prof. Christoph Klose, head of the Neuroimmune Interaction research group at the Institute of Microbiology and Infection Immunology at Charité and senior author of the study. “If we better understand the interplay of nerves, cells, and immune responses in the gut, we can develop more targeted and personalized medications—for example, for allergies, irritable bowel syndrome, or chronic inflammatory bowel diseases.” Furthermore, these reactions may potentially be addressed directly through diet. Therefore, as a next step, the team wants to determine precisely how nutrition can be used to support this neuro-gut axis and promote gut health.
*Jakob MO et al. Enteric nervous system-derived VIP restrains differentiation of LGR5+ stem cells toward the secretory lineage impeding type 2 immune program. Nat Immunol 2025 Nov 24. doi: 10.1038/s41590-025-02325-1