Gut immune sensing and physiological regulation

The intestine is a multifunctional organ responsible for nutrient absorption and host defense. As the primary interface interacting with the microbiota, the intestine maintains homeostasis via integrated sensing and responding to the lumenal environment through the intricate immune, endocrine, and neural networks. The intestinal immune system senses microbe-associated molecular patterns (MAMPs) and metabolites derived by the microbiota to modulate immune responses and immune effector production, which is essential to preserve the barrier integrity of the intestine. Meanwhile, immune effectors produced in the intestine could subsequently regulate physiological functions of the intestine and distal organs through circulatory and neural pathways. Although much remains unknown, accumulating evidence has implicated intestinal immune dysregulation in the pathogenesis of various diseases, such as inflammatory bowel diseases and metabolic disorders. This review will summarize our current understanding of intestinal immune sensing, immune effector production, and immune effector-mediated physiological regulation, thereby revealing the pivotal role of the intestinal immune system in organismal physiology and human health. These insights may provide a new perspective for the development of novel intervention strategies for intestine-related diseases.