Gut mechanoimmunology: Shaping immune response through physical cues

The gut immune system embodies a complex interplay between the gut mucosal barrier, the host's immune cells, and gut microbiota. These components exist within a dynamic environment characterized by a variety of physical cues, e.g., compression, tension, shear stress, stiffness, and viscoelasticity. The physical cues can be modified under specific pathological conditions. Given their dynamic nature, comprehending the specific effects of these physical cues on the gut immune system is critical for pathological and therapeutic studies of intestinal immune-related diseases. This review aims to discuss how physical cues influence gut immunology by affecting the gut mucosal barrier, host immune cells, and gut microbiota, defining this concept as gut mechanoimmunology. This review seeks to highlight that an enhanced understanding of gut mechanoimmunology carries therapeutic implications, not only for intestinal diseases but also for extraintestinal diseases.