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

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.

Metagenomic assessment of the Cebus apella gut microbiota

“…Functionally, in humans, the loose outer layer of the mucosal surface provides an area where the inhabiting bacteria can avoid washout from the flow of fluids through the intestinal tract. It also provides a source of energy for commensal bacteria that are able to degrade mucin glycans by releasing glycosyl hydrolases (Ravcheev & Thiele, ). The data presented here indicate that this may also be the case for the C. apella NHP.…”

Metaproteomics Reveals Potential Mechanisms by which Dietary Resistant Starch Supplementation Attenuates Chronic Kidney Disease Progression in Rats

“…We observed that RS supplementation, at least for the Ruminococcaeae family, results in a shift from fibrolytic family members to amylolytic family members that are well known butyrateproducers (Ruminococcus bromii, Ruminococcus torques). Typically, in the absence of sufficient dietary fibers, commensal and pathogenic bacteria start to forage on mucin glycans to harness carbon and energy (51,52).…”

High levels of fucosylation and sialylation of milk N‐glycans from mothers with gestational diabetes mellitus alter the offspring gut microbiome and immune balance in mice

“…Although direct mother‐to‐child bacterial transmission significantly contributes to the establishment of the neonatal microbiome, feeding pattern also has a major influence . Because gut microorganisms have differing abilities to utilize different types of glycans as carbon sources for growth and metabolism, differences in milk glycans may also affect the composition of the gut microbiome in the offspring. It has been shown that the milk N‐glycans of secretory immunoglobulin A (sIgA) and lactoferrin are affected by GDM, but not the HMOs .…”