IBD affects 1 in every 250 people in the UK, but its causes are unknown. Studies have shown that IBD patients have a different profile of gut microbes, which is called dysbiosis.
All of us have trillions of beneficial bacteria in our gut, but the combination of different species, known as the microbiome, varies. A crucial question has been whether IBD causes our microbiome to change, or whether an imbalanced microbiome could be triggering IBD. And exactly how does one affect the other? We need to study these interactions to define new targets for therapeutics.
Nathalie Juge and colleagues at the Institute of Food Research (IFR) have been trying to answer these questions by looking at the environment in which gut bacteria grow mucus. IFR is strategically supported by the Biotechnology and Biological Sciences Research Council.
Mucus covers the lining of our gut and provides an ideal environment for gut bacteria to grow by providing them with a rich source of sugars. However not all bacteria can consume mucus, and it’s been shown recently that IBD patients had a higher proportion of specific mucus-degrading bacteria called Ruminococcus gnavus, common gut bacteria found in most individuals.
Mucus is made up of long molecules, called mucins, which consist of protein chains, decorated with sugars, and usually capped with sialic acid, a sugar residue widely distributed in animal tissues. To use mucins, bacteria first have to remove the sialic acid. Once this is done, the sialic acid becomes available as a nutrient source for the whole of the bacterial community in the mucosal environment.
This means mucin-degrading bacteria have an important role in the whole bacterial community, so the researchers set out to work out what makes them effective.
Previously, the researchers found that R. gnavus’s ability to degrade mucins depended on the type of strain they were working with. So they then compared the genome sequences of these strains to identify which genes were behind the mucus-degrading abilities.
In a follow-up study, published in the journal Nature Communications, they found a surprising result. The cleavage enzyme allowing R. gnavus strains to grow on mucins, instead of releasing free sialic acid, chemically modifies it upon cleavage, providing these bacteria with a preferential source of nutrient.
This suggests a “selfish” behaviour where instead of sharing free sialic acid with other bacteria, R. gnavus mucin-degrader strains can use the modified sialic acid themselves.
This unusual activity hadn’t been seen in any other gut bacteria before. But having identified the enzyme, a bioinformatics screen found it in 11% of other bacteria. And the enzyme is also enriched in IBD patients, which agrees with previous studies showing an increased proportion of R. gnavus in IBD patients.
“We think that this enzyme may help the bacteria to adapt to changes occurring in IBD patients’ mucosal environment and give these bacteria a competitive nutritional advantage over others” said Dr Juge.
The researchers now need to determine the impact of these findings in a complex microbial community, but this study points the way beyond correlations between IBD and changes in the microbiota. Whilst it will be a while before this information could be used to develop new therapies, it could be developed into a better biomarker for IBD.
Notes to editors
Reference: “Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation” will be published in the journal Nature Communications at 10am BST UK time on Wednesday 8 July 2015 doi: 10.1038/ncomms7624.
About Institute of Food Research
The mission of the Institute of Food Research, www.ifr.ac.uk, is to be an international leader in research that addresses the fundamental relationships between food and health, food and the gut and the sustainability of the food chain in order to further the production of safe, healthy foods. It is a company limited by guarantee, with charitable status.
IFR is one of eight institutes that receive strategic funding from the Biotechnology and Biological Sciences Research Council. IFR received a total of £17.9M investment from BBSRC in 2013-14.
The institutes deliver innovative, world class bioscience research and training, leading to wealth and job creation, generating high returns for the UK economy. They have strong links with business, industry and the wider community, and support policy development.
The institutes’ research underpins key sectors of the UK economy such as agriculture, bioenergy, biotechnology, food and drink and pharmaceuticals. In addition, the institutes maintain unique research facilities of national importance.
Andrew Chapple, IFR
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