Advancements and Challenges in Modeling Mechanobiology in Intestinal Host-Microbiota Interaction

The gastrointestinal tract is a dynamic biomechanical environment where physical forces, cellular processes, and microbial interactions converge to shape the gut health and disease. In this review, we examine the unique mechanical properties of the gut, including peristalsis, viscoelasticity, shear stress, and tissue stiffness, and their roles in modulating host mechanosignaling and microbial behavior under physiological and pathological conditions. We discuss how these mechanical forces regulate gut epithelial integrity, immune responses, and microbial colonization, leading to distinct ecological niches across different intestinal segments. Furthermore, we highlight recent advancements in 3D culture systems and gut-on-a-chip models that accurately recapitulate the complex interplay between biomechanics and gut microbiota. By elucidating the intricate relationship between mechanobiology and gut function, this review underscores the potential for mechanotherapeutic strategies to modulate host-microbe interactions, offering promising avenues for the prevention and treatment of disorders such as inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer.