Intestinal Mucin Glycosylation: Structural Regulation, Homeostasis Maintenance and Disease Association.

The intestinal barrier is a complex configuration that defends against external assaults and maintains intestinal health. Disruption of barrier function can lead to intestinal inflammation and various diseases. Mucins are the primary structural components of the intestinal barrier, and their extensive glycosylation is critical for their protective function. Mucin glycans enhance the physicochemical integrity of the mucus barrier, protect against enzymatic degradation, modulate host immune responses, and shape the gut microbiota by providing adhesion sites and selective nutrient sources. While proper glycosylation maintains barrier integrity, supports a balanced microbial ecosystem, and limits unnecessary immune activation, its disruption leads to compromised barrier function, microbial dysbiosis, increased intestinal permeability, and ultimately contributes to the development of chronic colitis and colorectal cancer. Therefore, mucin glycosylation plays a crucial role in preserving intestinal barrier integrity and preventing colonic diseases. This review summarizes the classifications and structural features of intestinal mucin glycosylation, elucidates their roles in maintaining barrier function and their pathological alterations in intestinal disorders, and highlights the implications of mucin glycosylation for precision diagnosis and targeted therapy of intestinal diseases.