In an exciting new study published yesterday in the journal Nature Communications GHFS Research Leader Dr Nathalie Juge and her team have revealed an unusual enzymatic activity in gut bacteria Ruminococcus gnavus.
Below Nathalie blogs about the study, and how it could ultimately offer insights beyond correlations between Inflammatory Bowel Disease (IBD) and changes in the microbiota.
“Our study uncovers a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease.
The importance of the gut microbiota in modulating human health and disease has permeated many scientific disciplines, and raised a wide interest in the industry and the public. Importantly, there is an urgent need, yet to be addressed, to move from association or correlation studies to mechanistic studies. This is essential if we want to be in a position to devise meaningful strategies to modulate gut bacteria composition, especially at the mucosal interface where bacteria are likely to have highest impact on human health, due to their proximity to the host immune system.
The gastrointestinal (GI) mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the GI tract of more than 90% of healthy humans and overrepresented in inflammatory bowel diseases (IBD). In our previous work (Crost et al., 2013), we showed that the ability of R. gnavus to utilise mucin as carbon source was strain dependent. Here we showed, using a combination of genomics, enzymology and crystallography, that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal α2-3 linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid in the case of traditional sialidases. This IT-sialidase confers R. gnavus with a nutritional competitive advantage over its competitors, by preferentially accessing this nutrient rather than sharing free sialic acid with other members of the microbiota present in the mucosal environment. This is the first report of such enzymatic activity in the gut microbiota. Bioinformatics analyses revealed that IT-sialidases is not limited to R. gnavus but present across Firmicutes members. The specific niche colonization of these bacteria may reflect an adaptation to particular mucus glycosylation profiles. Indeed evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. This enzyme may thus represent a novel biomarker for IBD.
The molecular target (IT-sialidase), identified and characterized in our work, provides mechanistic insights into the adaptation of gut bacteria to changes in the mucosal environment occurring in IBD or during infection, and thus a lead for treating gut-related diseases. The experimental dissection of the IT-sialidase provides a structural basis for its role and a target that can be explored by all interested in the analysis of the human microbiome or specific bacterial strains.”
Written by Dr Nathalie Juge, July 2015