Comparative Genomic Analysis of the Human Gut Microbiome Reveals a Broad Distribution of Metabolic Pathways for the Degradation of Host-Synthetized Mucin Glycans and Utilization of Mucin-Derived Monosaccharides.

Dmitry A Ravcheev,Ines Thiele

doi:10.3389/fgene.2017.00111

Abstract

The colonic mucus layer is a dynamic and complex structure formed by secreted and transmembrane mucins, which are high-molecular-weight and heavily glycosylated proteins. Colonic mucus consists of a loose outer layer and a dense epithelium-attached layer. The outer layer is inhabited by various representatives of the human gut microbiota (HGM). Glycans of the colonic mucus can be used by the HGM as a source of carbon and energy when dietary fibers are not sufficiently available. Both commensals and pathogens can utilize mucin glycans. Commensals are mostly involved in the cleavage of glycans, while pathogens mostly utilize monosaccharides released by commensals. This HGM-derived degradation of the mucus layer increases pathogen susceptibility and causes many other health disorders. Here, we analyzed 397 individual HGM genomes to identify pathways for the cleavage of host-synthetized mucin glycans to monosaccharides as well as for the catabolism of the derived monosaccharides. Our key results are as follows: (i) Genes for the cleavage of mucin glycans were found in 86% of the analyzed genomes, which significantly higher than a previous estimation. (ii) Genes for the catabolism of derived monosaccharides were found in 89% of the analyzed genomes. (iii) Comparative genomic analysis identified four alternative forms of the monosaccharide-catabolizing enzymes and four alternative forms of monosaccharide transporters. (iv) Eighty-five percent of the analyzed genomes may be involved in potential feeding pathways for the monosaccharides derived from cleaved mucin glycans. (v) The analyzed genomes demonstrated different abilities to degrade known mucin glycans. Generally, the ability to degrade at least one type of mucin glycan was predicted for 81% of the analyzed genomes. (vi) Eighty-two percent of the analyzed genomes can form mutualistic pairs that are able to degrade mucin glycans and are not degradable by any of the paired organisms alone. Taken together, these findings provide further insight into the inter-microbial communications of the HGM as well as into host-HGM interactions.

Highlights

The colonic mucus layer is a dynamic and complex structure that is mainly composed of the glycoprotein mucin-2 (MUC2) (Johansson et al, 2008)
Mucin glycans are complex polysaccharides that contain five different monosaccharides, L-fucose (Fuc), D-galactose (Gal), N-acetyl-D-galactosamine (GalNAc), N-acetyl-D-glucosamine (GlcNAc), and N-acetylneuraminic acid (Neu5Ac), and can form various glycosidic bonds (Podolsky, 1985; Tailford et al, 2015). Degradation of such complex structures requires a large number of bacterial proteins interacting with the mucin glycans
All bacterial proteins involved in the degradation of mucin glycans were divided into two groups: (1) glycosyl hydrolases (GHs), which split glycans to oligo- and monosaccharides as well separating glycans from mucin proteins, and (2) enzymes required for the catabolism of the derived monosaccharides

Summary

Introduction

The colonic mucus layer is a dynamic and complex structure that is mainly composed of the glycoprotein mucin-2 (MUC2) (Johansson et al, 2008). Glycosylated MUC2 can form a gel-like structure due to its N- and C-terminal domains that form numerous crosslinks between cysteine residues (Johansson et al, 2013). Due to these cross-links, MUC2 forms a mucus structure. The colonic mucus consists of two layers, a loose outer layer and a dense epithelium-attached layer (Johansson et al, 2011). The inner layer acts as a physical barrier preventing bacteria from accessing the epithelium, whereas the outer layer is densely populated by various commensal microbes (Johansson et al, 2011, 2015; Li et al, 2015)

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