Mucin glycan foraging in the human gut microbiome

Louise E Tailford, Emmanuelle H Crost, Devon Kavanaugh, Nathalie Juge, Louise E Tailford, Emmanuelle H Crost, Devon Kavanaugh, Nathalie Juge

Abstract

The availability of host and dietary carbohydrates in the gastrointestinal (GI) tract plays a key role in shaping the structure-function of the microbiota. In particular, some gut bacteria have the ability to forage on glycans provided by the mucus layer covering the GI tract. The O-glycan structures present in mucin are diverse and complex, consisting predominantly of core 1-4 mucin-type O-glycans containing α- and β- linked N-acetyl-galactosamine, galactose and N-acetyl-glucosamine. These core structures are further elongated and frequently modified by fucose and sialic acid sugar residues via α1,2/3/4 and α2,3/6 linkages, respectively. The ability to metabolize these mucin O-linked oligosaccharides is likely to be a key factor in determining which bacterial species colonize the mucosal surface. Due to their proximity to the immune system, mucin-degrading bacteria are in a prime location to influence the host response. However, despite the growing number of bacterial genome sequences available from mucin degraders, our knowledge on the structural requirements for mucin degradation by gut bacteria remains fragmented. This is largely due to the limited number of functionally characterized enzymes and the lack of studies correlating the specificity of these enzymes with the ability of the strain to degrade and utilize mucin and mucin glycans. This review focuses on recent findings unraveling the molecular strategies used by mucin-degrading bacteria to utilize host glycans, adapt to the mucosal environment, and influence human health.

Keywords: O-glycosylation; carbohydrate; gastrointestinal tract; glycoside hydrolase; gut bacteria; gut health and disease; intestinal mucus; mucin degradation.

Figures

Figure 1
Figure 1
Schematic representation of GI mucus and mucins. The colonic epithelium is protected by mucin glycoproteins which are either membrane-attached (e.g., MUC1 and MUC4) or are secreted from goblet cells into the intestinal lumen (e.g., MUC2 and MUC5B). The secreted mucins further create a protective boundary in the form of a tightly-adherent mucus layer, which is devoid of bacteria, and a loosely-adherent mucus layer which provides a niche for intestinal bacteria.
Figure 2
Figure 2
Schematic representation of GI mucin glycans. (A) The four common mucin type O-glycans (core 1-8) found in the GI tract. (B) Main glycan epitopes in GI mucins. The glycan sugars are represented using Glycan Builder (Ceronietal., 2007).
Figure 3
Figure 3
O-glycan chains showing sites of action of GHs and sulfatases. Chain 1 is a hypothetical mucin glycan chain, chain 2 is O-GlcNAc often found on other glycoproteins, chain 3 (Tn antigen) and chain 4 are found in gastro-duodenal mucin.

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Source: PubMed

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