Spatiotemporal coordination between local flux and systemic homeostasis in the small intestine.

The small intestine has a pivotal role in nutrient absorption, host defense, and endocrine functions, with the maintenance of its homeostasis relying on the synergistic interplay of intrinsic and extrinsic factors. These encompass a highly organized spatiotemporal microenvironment, characterized by a regionalized histological architecture, functionally specialized cell populations, and spatially rhythmic nutrient gradient environments shaped by dietary patterns. While the link between small intestinal dysfunction and a wide range of systemic diseases has been well established, recent advances in spatial omics and dietary interventions have provided unprecedented new insights. Here, we review recent studies to systematically summarize the spatiotemporal regulatory mechanisms of small intestinal physiology, highlighting their important implications for the progression of inflammatory and metabolic diseases.