Enzyme discovered in the gut could lead to new disease biomarker

Date:
August 11, 2020
Source:
University of Birmingham
Summary:
Enzymes used by bacteria to break down mucus in the gut could
provide a useful biomarker for intestinal diseases, according to
new research.



FULL STORY ========================================================================== Enzymes used by bacteria to break down mucus in the gut could provide
a useful biomarker for intestinal diseases, according to new research
published in Nature Communications.


========================================================================== Researchers at the University of Birmingham and Newcastle University have successfully identified and characterised one of the key enzymes involved
in this process. They demonstrated how the enzyme enables bacteria to
break down and feed off sugars in the layers of mucus lining the gut.

The research offers a significant step forward in our understanding of
the complex co-dependent relationships at work in the gut, about which
little is currently known. Because the mechanism used by the enzyme is particularly distinctive, the researchers anticipate it can be used in
the development of new diagnostics for intestinal diseases.

The molecules in mucus, called mucin, are constantly produced by the
body to generate the layer of mucus in the gut that provides a barrier
between the gut's complex populations of bacteria and the rest of the
body. Mucin contain chains of sugar molecules called glycans, and these
also provide an essential source of nutrients for bacteria.

The team investigated how this enzyme sits on the outside of the bacterial
cell and clips away parts of the mucin molecule, taking them inside the bacterial cell to be consumed.

Because glycans are known to change when certain diseases are present
in the body, the researchers anticipate it will be possible to use the
enzymes to take a snapshot of the glycans within a biopsy and use that
as a biomarker for early detection of the disease.

Lead researcher, Dr Lucy Crouch, of the University of Birmingham's
School of Biosciences, explains: "Mucus is structured a bit like a
tree, with lots of different branches and leaves. Lots of the enzymes discovered so far might clip away some of the leaves to eat, but the
enzyme we studied will clip away a whole branch -- that's quite a
distinctive mechanism and it gives us a useful biomarker for studying
disease." The team have investigated this process in three different
diseases. They examined tissue from adults suffering from ulcerative
colitis and colorectal cancer, and from preterm infants with necrotising enterocolitis, a serious illness in which the gut becomes inflamed and
can start to die. They found that by adding the enzyme to the samples
and labelling the glycans with a fluorescent dye, they were able to get
useful information about the glycan structure.

Dr Crouch adds: "Although we still don't fully understand what the glycan structures are made from and how these vary between different tissue
types, we can see that the differences in structure between health and non-healthy tissue is quite distinctive. We hope to be able to use these enzymes to start producing better diagnostics for the very early stages
of these diseases."

========================================================================== Story Source: Materials provided by University_of_Birmingham. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Lucy I. Crouch, Marcelo V. Liberato, Paulina A. Urbanowicz, Arnaud
Basle', Christopher A. Lamb, Christopher J. Stewart, Katie
Cooke, Mary Doona, Stephanie Needham, Richard R. Brady, Janet
E. Berrington, Katarina Madunic, Manfred Wuhrer, Peter Chater,
Jeffery P. Pearson, Robert Glowacki, Eric C. Martens, Fuming Zhang,
Robert J. Linhardt, Daniel I. R.

Spencer, David N. Bolam. Prominent members of the human
gut microbiota express endo-acting O-glycanases to initiate
mucin breakdown. Nature Communications, 2020; 11 (1) DOI:
10.1038/s41467-020-17847-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200811120139.htm

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