By Diagnostics World News Staff
December 18, 2025 | Researchers have identified a previously overlooked mechanism controlling allergic reactions in the gut, potentially paving the way for novel treatments for conditions ranging from food allergies to irritable bowel syndrome.
The study, led by Manuel Jakob, M.D., a clinician-scientist at Charité -- Universitätsmedizin Berlin, reveals that vasoactive intestinal peptide (VIP) acts directly on intestinal stem cells to suppress allergy-like immune responses. The findings, published in Nature Immunology, challenge previous assumptions about how the gut's nervous system regulates immune function.
When Jakob's team deleted VIP in mice, they observed a dramatic increase in four secretory cell types—tuft, goblet, Paneth, and stem cells—creating an allergy-like response in the animals. The discovery came as a surprise, as the researchers had initially hypothesized that VIP would trigger these responses through a different receptor pathway.
Instead, they found that VIP suppresses stem cell differentiation into secretory epithelial cells by working through the VIPR1 receptor on the epithelium, rather than through VIPR2 receptors on immune cells as expected.
The Diagnostic Implications
The research sheds new light on why some individuals experience heightened gut sensitivity and allergic responses. The enteric nervous system—the network of nerve cells controlling digestive functions—appears to act as a sophisticated interface between the body's internal environment, the gut microbiome, and the central nervous system.
This neuro-epithelial-immune circuit could serve as a diagnostic marker for conditions involving type 2 immune responses. Understanding how VIP levels and receptor activity influence gut reactivity may help clinicians identify patients at risk for food allergies, inflammatory bowel conditions, and related disorders.
The ability of VIP to suppress allergy-like responses suggests potential therapeutic applications for diseases involving type 2 immune reactions, including irritable bowel syndrome and food allergies. Jakob envisions future treatments that could directly deliver VIP or similar compounds via oral administration.
Perhaps most intriguingly, the research revealed a dietary intervention with immediate implications. Mice showing allergy-like responses improved when switched from solid to liquid diets, suggesting that food consistency and formulation play critical roles in immune activation.
Jakob's team plans to investigate how nutrition can be strategically deployed to support intestinal health, examining how different foods influence neuron activation and VIP function. The research will employ knockout rodent models and human intestinal organoid cultures to better understand these mechanisms.
As Jakob notes, if researchers can better understand how immune responses are coordinated at the highest level, they may be able to tackle many diseases in the future. The work represents a significant step toward harnessing the gut's own regulatory systems for therapeutic benefit—potentially offering patients relief through approaches as simple as dietary modification or as targeted as peptide-based pharmaceuticals.