The role of mucin O-glycans in microbiota dysbiosis, intestinal homeostasis, and host-pathogen interactions.

Abstract

Mucin O-linked glycans are important mediators of host-microbiota-pathogen interactions in the gastrointestinal tract. The major component of intestinal mucus, the MUC2 mucin, is densely glycosylated, with up to 80% of its weight-to-volume ratio represented by O-linked glycans. Glycosylation of secretory gel-forming mucins has an enormous impact on intestinal barrier function, microbial metabolism, and mucus colonization by both pathogenic and commensal microbes. Mucin O-glycans and glycan-derived sugars may be degraded and used as a nutrient source and may regulate microbial gene expression and virulence. Short-chain fatty acids, produced as a by-product of glycan fermentation, can regulate host immunity and goblet cell activity and are important for host-microbe homeostasis. Mucin glycans may also act as microbial binding sites, influencing intestinal colonization and translocation through the mucus gel barrier. Recent findings indicate that alterations to mucin glycosylation impact the susceptibility of mucins to degradation, resulting in altered barrier function and intestinal permeability. Alterations to mucin glycosylation patterns are frequently observed during intestinal infection and inflammation and have been implicated in microbiota dysbiosis and expansion of pathobionts. Recent work has demonstrated that these alterations can play key roles in disease pathogenesis. The precise mechanisms remain obscure. This review highlights the important roles of O-linked glycans in host-microbe interactions and disease pathogenesis in the context of intestinal infections.