Propolis has been used for medicinal purposes since ancient times, and recently it has become well established as a health food with a variety of benefits, including anti-inflammatory effects through activation and control of the immune system. We have established a cell lineage-specific calcium biosensor mouse line and a system for real-time visualization of not only immune cell dynamics but also activation using intravital imaging, as well as intestinal sensing of food signals. This facilitates highly sensitive evaluation of the effects of food. Using this system, we have shown that propolis directly stimulates dendritic cells and B cells and exhibits adjuvant activity. In addition, propolis intake increased the activation of dendritic cells in Peyer's patches of the small intestine. It was also suggested that propolis may induce a food signal in small-intestinal epithelial cells, and exert an anti-inflammatory effect via the brain-gut axis mediated by the vagus nerve.