The microbiota, comprising trillions of microbes residing in the gut lumen, profoundly influences host health and disease. In my years of veterinary practice, I frequently encountered conditions caused by disruptions in microbiota and recognized the limitations of available treatments for these animals. Now, as a basic science researcher, I strive to understand the complexity of the host-nutrition–microbiota interplay, with the goal of contributing to the development of effective microbiota-based interventions. In this seminar, I will present recent advances in epithelial biology and intestinal immunity regulated by the microbiota including my own research and discuss their potential relevance to domestic animal species.