Mechanisms and therapeutic perspectives of mucosal glycosylation-innate immunity crosstalk in inflammatory bowel disease (Review)

Inflammatory bowel disease (IBD) is a group of chronic, relapsing inflammatory disorders of the gastrointestinal tract, driven by a complex interplay of genetic susceptibility, environmental exposures, intestinal microbiota dysbiosis and immune dysregulation. In recent years, mucosal glycosylation has emerged as a fundamental molecular determinant of intestinal barrier integrity and function and is increasingly recognized as a key regulatory interface linking the microbiota with host immune responses. Concurrently, the innate immune system serves an important role in mucosal defense and inflammatory responses through pattern recognition receptor‑mediated signaling, and its aberrant activation represents a key driver of persistent inflammation in IBD. The present review systematically summarizes the bidirectional regulatory crosstalk between mucosal glycosylation and innate immunity. The mechanistic roles of glycosylation modifications are highlighted in pathogen recognition, inflammatory signal transduction, inflammasome activation and maintenance of mucosal barrier integrity. Conversely, it is discussed how innate immune activation regulates glycan biosynthesis and remodeling through inflammatory cytokines, oxidative stress and major signaling pathways, thereby reshaping the mucosal glycome in disease contexts. On this basis, the dynamic alterations of glycosylation‑innate immunity interactions across different stages of IBD, including disease initiation, progression and relapse, are delineated, emphasizing their important role in sustaining chronic inflammation and driving tissue remodeling. In addition, emerging therapeutic strategies targeting glycosylation pathways, glycan‑lectin interactions, mucosal barrier restoration and microbiota modulation are summarized. The potential of glycomics, multi‑omics integration and glyco‑immune biomarkers in disease stratification and precision medicine are also discussed. By integrating perspectives from glycobiology and immunology, the present review aims to provide a conceptual framework and novel directions for mechanistic research and targeted therapy in IBD.