Polysaccharides in Gastric Mucosal Homeostasis: From Multistage Defense Mechanisms to Structural Determinants.

The stomach is the first major site where dietary and therapeutic polysaccharides encounter a highly acidic and mucus-rich dynamic environment, yet this gastric phase has received far less attention than their downstream actions in the intestine. This gap is important because gastric mucosal homeostasis depends on a coordinated multistage defense system involving the mucus-glycoprotein barrier, epithelial junctional integrity, oxidative and inflammatory control, regulated cell death, restitution and regeneration, and balanced gastric microecology. Among natural bioactive alternatives, polysaccharides are especially attractive because they combine intrinsic biological activity with remarkable structural and material versatility. In this review, we propose a stomach-centered framework for understanding polysaccharides in gastric mucosal homeostasis. We summarize how polysaccharides act across multiple defensive stages by reinforcing the mucus barrier, stabilizing epithelial function, attenuating oxidative stress and inflammatory amplification, modulating cell death and the immune microenvironment, promoting restitution and high-quality healing, and interfering with Helicobacter pylori colonization and dysbiosis. We further emphasize how molecular weight, charge, monosaccharide composition, linkage pattern, branching architecture, advanced conformation, and delivery-related engineering jointly determine the depth, location, and durability of gastric protection. This framework may guide the rational design of next-generation polysaccharide-based strategies for precise and durable gastric mucosal repair.