Intestinal interoception: A nexus of environment-body-brain interactions

The interoceptive system senses changes in internal states and initiates body-brain feedback loops, which lead to physiological and behavioral adaptations to varying environmental conditions. Recent advances in the field have uncovered specific cell types and circuits involved in homeostatic interoception, how these circuits respond to environmental factors, and how dysfunction in body-brain interactions contributes to disease pathogenesis. Here, we summarize the major anatomical and functional principles of interoception, with a particular focus on communication between the gastrointestinal tract and the brain. In addition, we provide several examples of how environmental and lifestyle factors impact gut-brain signaling. Finally, we explore interoceptive dysfunction as a common characteristic of numerous major human diseases. We outline steps toward the development of interoceptomimetics-molecular interventions that stimulate the transmission of signals between the body and the brain, with the goal of restoring organismal homeostasis.