Management of the human mucosal defensive barrier: evidence for glycan legislation

Abstract

The human gastrointestinal barrier comprises several layers which enable protection against the external environment. The mucosal epithelium, lamina propria, glycocalyx and secreted mucus each make a contribution to barrier protection. Glycocalyx and secreted mucins constitute a glycosylated environment which interacts with the enteric microflora. Turnover of the mucus layer and the creation of binding ligands for bacteria are significant factors in gut homeostasis. The gut microbiota is composed of many bacterial species, but improved technology has allowed detection of populations present at different stages of development and in disease. Interaction of the microflora with the gut occurs from birth onwards and enables maturation of gut angiogenesis and glycosylation as demonstrated in mouse models. Glycan legislation regulates the ongoing interaction between the microflora and the host mucosa. This accounts for host glycosylation mechanisms providing a dynamic response to fluctuations in the gut microflora. Evidence for glycan legislation is based on a surgical model where intact mucosa can be compared with and without contact to the faecal microflora. In addition, mucosal cell glycosylation is assessed using inhibitors of O-glycan synthesis. These inhibitors lead to growth arrest in cultured colorectal cancer cell lines through the induction of apoptosis and downregulation of proliferation.