Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent

Abstract

Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease.

Aeromonas salmonicida Growth in Response to Atlantic Salmon Mucins Differs between Epithelial Sites, Is Governed by Sialylated and N -Acetylhexosamine-Containing O -Glycans, and Is Affected by Ca 2+

“…Sialidase activity of A. salmonicida was analyzed with the modified method of Crost et al (19). Briefly, 20 l of fresh A. salmonicida liquid culture was added to a reaction mixture consisting of 500 M 4MU-Neu5Ac (Sigma-Aldrich Co.) as a substrate in PBS, pH 7.4.…”

“…Mucins can bind pathogens and can modulate bacterial growth, e.g., via stimulatory or inhibitory glycan motifs (17,18) and/or by being food sources for bacteria through released glycans (19). The ability of the mucin glycan structures to bind bacteria plays an important role in the mucosal defense against infection (15,20).…”

Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

“…This included common gut commensals such as Dorea longicatena and Dorea formicigenerans, where higher species abundances were connected to higher IFNγ levels in response to C. albicans hyphae. Both Dorea species can metabolize sialic acids, which are commonly found at terminal ends of mucins; release of these acids is implicated in mucin degradation, potentially increasing gut permeability (Crost et al, 2013). In contrast, another unclassified Dorea species was negatively correlated with the IFNγ response.…”

Escherichia coli O157:H7 Strain EDL933 Harbors Multiple Functional Prophage-Associated Genes Necessary for the Utilization of 5- N -Acetyl-9- O -Acetyl Neuraminic Acid as a Growth Substrate

“…In the mucin, they play a role in protection of the core protein against microbes. Nevertheless, there are some anaerobes which can remove the sialic acids from the glycoprotein by sialidases (40)(41)(42). Mostly, sialidases are specialized to cleave only a few bonds of sialic acids to the glycoprotein or to have narrow substrate specificity.…”