Intestinal mucus and their glycans: A habitat for thriving microbiota

Abstract

The colon mucus layer is organized with an inner colon mucus layer that is impenetrable to bacteria and an outer mucus layer that is expanded to allow microbiota colonization. A major component of mucus is MUC2, a glycoprotein that is extensively decorated, especially with O-glycans. In the intestine, goblet cells are specialized in controlling glycosylation and making mucus. Some microbiota members are known to encode multiple proteins that are predicted to bind and/or cleave mucin glycans. The interactions between commensal microbiota and host mucins drive intestinal colonization, while at the same time, the microbiota can utilize the glycans on mucins and affect the colonic mucus properties. This review will examine this interaction between commensal microbes and intestinal mucins and discuss how this interplay affects health and disease.

Keywords: colon; colonization; commensal bacteria; intestine; mucin, glycans; mucus.

Figure 1.

The main building block of intestinal mucus and bacterial source of O-glycans, the MUC2 mucin.

Figure 2.. The mucus layers of small and large intestine.

Anti-bacterial compounds secreted by the Paneth cells together with the mucus keep bacteria from the epithelium in the small intestine. The inner mucus layer of colon is formed by mucins and other molecules from the icGC and crypt GC to generate a bacterial barrier. The commensal bacteria live and utilize the mucins of the outer colon mucus layer. Created with BioRender.com

Figure 3.. The goblet cell mucin biosynthesis and glycosylation.

(A) Goblet cell with organization of the glycosylation machinery. (B) QSOX1 activates sialyltransferase ST6Gal1 by oxidation of cysteines forming two disulfide bonds.

Figure 4.. Commensal bacteria utilization of host O-glycans.

(A) Human milk oligosaccharides (HMOs) are structurally similar to mucin O-glycans. Some commensal bacteria evolved to utilize HMOs and O-glycans as a carbon source. (B) Schematic representation of five B. theta polysaccharide utilization loci (PULs) upregulated during growth on HMOs and mucin O-glycans. (C) Representation of the specificity of characterized O-glycan active enzymes. The arrows point to the linkage cleaved by the different enzymes. Glycoside hydrolases, sulfatases, and carbohydrate esterase are shown inside blue, green and gray boxes, respectively. Sugars are shown according to the Symbol Nomenclature for Glycan System. GHXXX, glycoside hydrolase family XXX.

Figure 5.

Bacterial binding proteins will recognize single glycan epitopes or more likely mucin glycan patches.