Molecular Insights Into O-Linked Glycan Utilization by Gut Microbes

Abstract

O-linked glycosylation is a post-translational modification found mainly in eukaryotic cells, which covalently attaches oligosaccharides to secreted proteins in certain threonine or serine residues. Most of O-glycans have N-acetylgalactosamine (GalNAc) as a common core. Several glycoproteins, such as mucins (MUCs), immunoglobulins, and caseins are examples of O-glycosylated structures. These glycans are further elongated with other monosaccharides and sulfate groups. Some of them could be found in dairy foods, while others are produced endogenously, in both cases interacting with the gut microbiota. Interestingly, certain gut microbes can access, release, and consume O-linked glycans as a carbon source. Among these, Akkermansia muciniphila, Bifidobacterium bifidum, and Bacteroides thetaiotaomicron are prominent O-linked glycan utilizers. Their consumption strategies include specialized α-fucosidases and α-sialidases, in addition to endo-α-N-acetylgalactosaminidases that release galacto-N-biose (GNB) from peptides backbones. O-linked glycan utilization by certain gut microbes represents an important niche that allows them to predominate and modulate host responses such as inflammation. Here, we focus on the distinct molecular mechanisms of consumption of O-linked GalNAc glycans by prominent gut microbes, especially from mucin and casein glycomacropeptide (GMP), highlighting the potential of these structures as emerging prebiotics.

The Role of Fucose-Containing Glycan Motifs Across Taxonomic Kingdoms

“…However, proteins such as mucins also exist in invertebrates and seem to carry different O -linked glycans than those in vertebrates ( Staudacher, 2015 ), suggesting the need for more research in this area. In vertebrates, O -linked glycans are important for the immune system and for the synthesis of mucus ( Giovannone et al, 2018 ; Nason et al, 2021 ), a substance modulating pathogen adherence in animals ( Gonzalez-Morelo et al, 2020 ). As a consequence, disruption of this type of glycosylation is associated with many human diseases ( Hansson, 2019 ).…”

Global functions of O‐glycosylation: promises and challenges in O‐glycobiology

“…cleave the protein backbone [191,192], while some other species of the gut microbiota degrade and feed on O-glycans [193,194]. Enveloped viruses represent another unique category of microbes that have evolved to mimic host glycosylation in order to evade host immunity, which is most commonly attributable to N-linked glycans [195,196].…”

Structure and evolution of the bifidobacterial carbohydrate metabolism proteins and enzymes

“…Long-term coevolution was likely established due to a mutually beneficial relationship between the human host and the mucin-adherent microbiota [ 61 ]. Strains of B. longum , B. bifidum , and B. breve possess glycosidases targeting O -linked mucin glycans [ 62 , 63 ]. The three-dimensional structures of two bifidobacterial mucin-degrading enzymes have been reported.…”