A vagal gut-brain axis for feeding-induced gastric secretion in mice.

Feeding begins with food-seeking and ends with nutrient absorption and waste elimination. Although meal-related sensory cues shape feeding behavior, how they engage neural circuits to control digestion remains unclear. We dissected vagal gut-brain-gut pathways mediating meal-induced gastric secretion. Stomach-innervating vagal afferents were necessary and sufficient for secretion. Among them, Glp1r+ and Sst+ neurons drove acid, pepsin, and gastrin secretion, whereas Oxtr+ and Vip+ neurons had little effect. Piezo2 was expressed in Glp1r+ mechanosensory afferents, and conditional deletion of Piezo2 attenuated distension-evoked secretion. On the efferent limb, genetically defined vagal motor-neuron subsets showed distinct secretory effects: Cck+ neurons broadly increased acid, pepsin, and gastrin, whereas Grp+ neurons preferentially affected acid secretion. Finally, enteric circuit dissection revealed modular output control, with Calb2+ neurons driving secretion with minimal motility effects. Together, these results define a cell-type-resolved vagal-enteric architecture for gastric control.