Mucosal glycans: key drivers of the development of inflammatory bowel disease and a potential new therapeutic target

Glycans are essential components of homeostatic networks, acting as fine tuners of immunological responses, and are therefore promising targets for manipulating immune tolerance. Glycans shield the entire gut mucosa surface, contributing to epithelial barrier integrity. Moreover, most microorganisms expose glycoconjugates on their surfaces, making glycans essential molecules in the crosstalk between host immune response and the gut microbiota. The vast amount of biological information encoded by mucosal glycans is deciphered by a variety of glycan-binding proteins that translate glycan recognition into either pro-inflammatory or anti-inflammatory responses. Current evidence from inflammatory bowel disease (IBD) has highlighted the prominent role of glycans in establishing and regulating key cellular and molecular pathways underlying the transition from health to intestinal inflammation, with implications for understanding IBD immunopathogenesis and for IBD prediction and prevention. In this Review, we discuss current advances, emerging challenges and future prospects in exploiting the power of the mucosal glycocalyx and the glycome as master coordinators of the immunoregulatory networks in IBD from the preclinical phase to established diagnosis. We discuss the clinical utility of the glycome as a serological biomarker with diagnostic, prognostic and predictive value, and as a potential new target for preventive intervention strategies in IBD.