The role of glycosylation in IBD

Abstract

A number of genetic and immunological studies give impetus for investigating the role of glycosylation in IBD. Experimental mouse models have helped to delineate the role of glycosylation in intestinal mucins and to explore the putative pathogenic role of glycosylation in colitis. These experiments have been extended to human studies investigating the glycosylation patterns of intestinal mucins as well as levels of glycans of serum glycoproteins and expression of glycan receptors. These early human studies have generated interesting hypotheses regarding the pathogenic role of glycans in IBD, but have generally been restricted to fairly small underpowered studies. Decreased glycosylation has been observed in the intestinal mucus of patients with IBD, suggesting that a defective inner mucus layer might lead to increased bacterial contact with the epithelium, potentially triggering inflammation. In sera, decreased galactosylation of IgG has been suggested as a diagnostic marker for IBD. Advances in glycoprofiling technology make it technically feasible and affordable to perform high-throughput glycan pattern analyses and to build on previous work investigating a much wider range of glycan parameters in large numbers of patients.

Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia

“…As a result, we found that many pathways that have previously been implicated in ASD (dioxin degradation [41], steroid hormone biosynthesis [42]) were altered in the same manner in ASD mice (Fig. 4a, Table 2), as well as those implicated in IBD (sulfur metabolism [43], N-Glycan biosynthesis; [44] Table 2). Notably, lipopolysaccharide (LPS) biosynthesis and bacterial toxin have been implicated in the pathogenesis of both ASD [45] and IBD; [46] accordingly, our results showed that both poly I:C and VPA mice have significant up-regulations in pathways involving LPS biosynthesis and bacterial toxins (Fig.…”

The Vat-AIEC protease promotes crossing of the intestinal mucus layer by Crohn's disease-associatedEscherichia coli

“…Thus, MUC2 degradation by Vat-AIEC-producing AIEC might be promoted in presence of these mucinolytic bacteria. Besides, there is a range of glycosylation abnormalities in CD patients, including reduced length of O-glycans (Bodger et al, 2006;Rhodes et al, 2008), and genetic studies implicate genes involved in glycosylation pathways as CD susceptibility loci (Theodoratou et al, 2014). For example, single nucleotide polymorphisms in the FUT2 gene, which encodes an α(1,2)fucosyltransferase that catalyses Vat-AIEC Favours Mucus Layer's Crossing by LF82 E. coli 625 addition of terminal α(1,2)fucose residues on mucins and other molecules in mucosal epithelium, have been found to be associated with CD (McGovern et al, 2010).…”

Characterizing the O-glycosylation landscape of human plasma, platelets, and endothelial cells

“…7 Recent glycoproteomics studies in cell lines, however, indicate that, far from being specific to mucin-like regions, O-glycosylation is a ubiquitous PTM and .80% of proteins trafficking through the secretory pathway are estimated to be O-glycosylated. 1,8 Furthermore, it is likely that O-glycans play a role in diverse physiologic systems because altered O-glycosylation is associated with IgA nephropathy, 9 Tn syndrome, 10 Crohn disease, 11 tumorigenesis, 12 impaired leukocyte recruitment, 13 and high-density lipoprotein levels. 14 Dissection of the molecular mechanisms by which O-glycans affect these systems is, however, currently impeded by a lack of knowledge of specific O-glycan sites in vivo.…”