Mucin glycan foraging in the human gut microbiome

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.

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

“…We further noted an increased abundance of A. muciniphila in infected subjects. This bacterium has been implicated in mucin degradation (38,39) and increased susceptibility to infection (40,41). Since Cryptosporidium sporozoites initiate infection via contact with enterocyte membranes, an increase in the %RA of Akkermansia found may erode the protective mucin covering, thus increasing the opportunity for sporozoite binding.…”

Genomics of the Genus Bifidobacterium Reveals Species-Specific Adaptation to the Glycan-Rich Gut Environment

“…The main monosaccharide components in mucin-derived glycoproteins are N-acetylglucosamine, N-acetylgalactosamine, and galactose, and these glycoproteins are decorated with fucose, sialic acid, and sulfate groups (51). Within the genus Bifidobacterium, only members of the B. bifidum species have been shown to efficiently degrade mucin (48,52,53).…”

Automated and accurate estimation of gene family abundance from shotgun metagenomes

“…Gene families driving this enrichment included alpha-L-fucosidases (K01206, q = 0.047; K15923, q = 0.096), galactosidases (K01190, q = 0.064; K12111, q = 0.066), and sialidase (K01186, q = 0.077), which are all classes of enzymes that have been implicated in mucin degradation [60], as well as the hexosaminidase family (K12373, q = 0.066), which is also annotated to the pathway "glycosaminoglycan degradation." Mucins and glycosaminoglycans (GAGs) are classes of glycoproteins associated with the epithelia of the GI tract and help to maintain its integrity and regulate its permeability.…”