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.

An Overview of the Immunological Defenses in Fish Skin

“…Based on biochemical characterisation, nineteen genes are currently assigned to the mucin family (see [337,338]) and are named "MUCnumber" for humans or "Muc-number" for other species [112]. Mucin genes typically possess repetitive region/s which is/are the sites where glycosylation takes place [339].…”

A Biliary HCO3 − Umbrella Constitutes A Protective Mechanism Against Bile Acid–Induced Injury in Human Cholangiocytes

“…24 This ''sugary'' layer mediates cell-cell recognition, receptor-ligand interactions, and adds to the barrier function of the plasma membrane, as best characterized for the endothelial 25 and intestinal glycocalyx. [26][27][28] This juxtamembranous layer may locally alter the pH near, but exterior, to the lipid bilayer. In melanoma cells, the pH measured in the glycocalyx was reported to be slightly higher than the pH of the medium, and the absolute number of H þ molecules differed up to 40% between different domains of the glycocalyx of a single cell.…”

Mucosal Adhesion Properties of the ProbioticLactobacillus rhamnosusGG SpaCBA and SpaFED Pilin Subunits

“…Often a necessary precondition for colonization of the human gastrointestinal (GI) tract by probiotic bacteria is preferential adherence to the intestinal mucosa, which in turn prolongs and stabilizes intestinal residence, possibly triggering a variety of defensive host cell immune responses and excluding pathogenic bacteria by competitive inhibition or steric hindrance (48). The outermost layer of the intestinal mucosa, which is a secreted and hydrated mucus gel that acts as a protective barrier and filter, consists primarily of a heterogeneous mixture of highly glycosylated membrane-associated and secreted glycoproteins called mucins (36). Although many studies have demonstrated that various probiotic Lactobacillus spp.…”