Scientists have uncovered a previously unknown communication system in the gut that helps determine whether the immune system goes into attack mode or repair mode, and it appears to be tied to when we eat.
The findings, published in Nature Immunology, come from mouse studies led by researchers at the Champalimaud Centre for the Unknown in Portugal. The work sheds new light on how eating patterns may influence gut immunity and inflammation, though the authors emphasize that the mechanisms have not yet been tested in humans.
“The gut isn’t just a tube that digests food — it’s a highly active organ where the nervous and immune systems are in constant conversation,” said senior author Henrique Veiga-Fernandes.
The team focused on a neurochemical called vasoactive intestinal peptide, or VIP, which is released by certain neurons in the digestive tract. They found that neighboring epithelial cells, the cells that line the gut, carry a receptor for VIP that acts almost like an antenna. When VIP rises, typically after eating, these epithelial cells send out signals that activate a type 1 immune response, the arm of the immune system designed to eliminate bacteria and infected cells.
Blocking the VIP receptor flipped the response entirely. Instead of gearing up for attack, the gut shifted toward type 2 immunity, a repair-oriented pathway that supports tissue recovery and helps fight parasites. According to first author Roksana Pirzgalska, this meant mice became more vulnerable to bacterial infection but more resistant to parasitic worms.
The researchers describe this system as a kind of internal “switch,” with gut neurons helping steer immunity toward either defending or repairing. What pushes the switch appears to be closely tied to feeding. Meals naturally trigger VIP release, a useful evolutionary response, the authors note, because eating brings potential exposure to pathogens.
The results also raise questions about how modern eating patterns may affect gut balance. The study suggests that irregular schedules or late-night meals could disrupt the normal rhythm between immune activation and repair, though human studies are needed to test this idea.
“Our findings suggest that when circadian rhythms and feeding patterns are out of sync, the gut’s neuro-immune switch may be mis-timed,” Veiga-Fernandes said.
To explore whether a similar system exists in people, the team examined human intestinal tissue and found that epithelial cells also carry the VIP receptor. That doesn’t prove humans respond the same way, but it suggests the basic wiring may be shared.
The researchers are now investigating how signals from the brain interact with these gut circuits and whether similar immune “switches” operate in other organs.
Because this research was conducted in mice, more studies are needed to understand what these findings mean for human gut health and whether eating patterns can influence immune balance in similar ways.
This study was supported by multiple European research agencies and foundations, including the Champalimaud Foundation, the European Research Council, France’s national funding agencies, Germany’s DFG, the European Crohn’s and Colitis Organisation, and the U.S. National Institute of Allergy and Infectious Diseases.