Epithelial glycosylation in gut homeostasis and inflammation

Intestinal epithelial cells apically express glycans, especially alpha 1,2-fucosyl linkages, which work as a biological interface for the host microbe interaction. Emerging studies have shown that epithelial alpha 1,2-fucosylation is regulated by microbes and by group 3 innate lymphoid cells (ILC3s). Dysregulation of the gene (FUT2) encoding fucosyltransferase 2, an enzyme governing epithelial alpha 1,2-fucosylation, is associated with various human disorders, including infection and chronic inflammatory diseases. This suggests a critical role for an interaction between microbes, epithelial cells and ILC3s mediated via glycan residues. In this Review, using alpha 1,2-fucose and Fut2 gene expression as an example, we describe how epithelial glycosylation is controlled by immune cells and luminal microbes. We also address the pathophysiological contribution of epithelial alpha 1,2-fucosylation to pathogenic and commensal microbes as well as the potential of alpha 1,2-fucose and its regulatory pathway as previously unexploited targets in the development of new therapeutic approaches for human diseases.