Optogenetics-integrated gut organ culture system connects enteric neurons dynamics and gut homeostasis

The enteric nervous system senses microbiota-derived signals and orchestrates mucosal immunity and epithelial barrier functions. Mechanistic dissections of intestinal neuro-immune-microbiota communications remain challenging. We developed an optogenetics-integrated gut organ culture system for real-time neuronal stimulation and analysis. We revealed neuronal-specific activity patterns, which differentially regulate intestinal transcription and epithelial barrier integrity. Collectively, we provide a powerful platform to test neuroimmune connections and their potential modulation by drugs, microbes, or metabolites.