An absorptive epithelial lining of the gut is the fundamental structure defining all animals throughout evolutionary history. Intestinal epithelial barriers are typically colonized by a community of bacterial symbionts (microbiota) that engage in nutrient exchange with the host to their mutual benefit. While this interface has been extensively studied in terms of antimicrobial factors and microbial pathogenesis, most bacteria-epithelial interactions are benign. By studying processes of molecular symbiosis that maintain health, we may learn new biology, uncover new strategies to prevent disease at its cellular origin, and inform the design and deployment of microbe-based therapeutics.