Mucus and mucins may become the medicine of the future

Date:
July 7, 2021
Source:
University of Copenhagen - The Faculty of Health and Medical
Sciences
Summary:
The body is filled with mucus that keeps track of the bacteria. Now,
researchers present a method for producing artificial mucus. They
hope that the artificial mucus, which consists of sugary molecules,
may help to develop completely new, medical treatments.



FULL STORY ==========================================================================
Many people instinctively associate mucus with something disgusting,
but in fact, it has incredibly many valuable functions for our health. It
keeps track of our important intestinal flora and feeds the bacteria. It
covers all internal surfaces of our body, and, as a barrier to the
outside world, it helps us protect ourselves from infectious diseases.


==========================================================================
This is because mucus acts as a filter that keeps the bacteria in or out,
and the bacteria feed on the sugars in the mucus between meals. So,
if we can produce the mucus that is already present in the body with
the right sugars, it might be used in brand new medical treatments.

Now, researchers from the DNRF Centre of Excellence, Copenhagen Center for Glycomics, have discovered how to artificially produce the healthy mucus.

'We have developed a method for producing the important information found
in human mucus, also called mucins, with their important sugars. Now,
we show that it is possible to artificially produce it in the same way
as we produce other therapeutic biologics today, such as antibodies and
other biological medicine', says Professor Henrik Clausen, lead author
of the study and Director of the Copenhagen Center for Glycomics.

The mucus, or mucins, consist mostly of sugars. In the study, the
researchers show that it is actually special patterns of sugars on the
mucins that the bacteria recognise.

'It is the body's way of selecting the good bacteria and deselecting
those that cause diseases. And it is precisely the sugars in the mucus
that we are now able to design as needed', says first author of the study, Ph.D. student Rebecca Nason.



==========================================================================
The researchers are particularly interested in the mucus in the gastrointestinal tract. Like a giant fishing net, the mucus keeps track of
all the bacteria, our microbiome, down there. So, if one could imitate the ability of bacteria to attach to the intestinal mucus, one could design
oral medications that stick to the mucus, making them more effective.

'We have found a small molecule from bacteria -- which we call X409 --
that binds to the intestine, and that is precisely one of the many possibilities we are now working on', says Rebecca Nason.

It can be difficult to get medicine to be effective when it has to be
ingested and absorbed into our intestinal system. So, when you design
your drug as a pill that the patient swallows, it is not certain that
it will be fully efficient.

There are many obstacles on the way down through the digestive system,
and the medication needs time in the gastrointestinal tract to be
dissolved and distributed in the body', explains Rebecca Nason.

We swallow more than a litre of mucus in the form of saliva per day and
more from the stomach, which together with the ever-changing fishing
net of mucus in the intestine feed our intestinal microbiome. The
microbiome of the intestine is absolutely crucial to our health and of
great importance in relation to many diseases.



==========================================================================
'An incredible number of diseases have a connection to the intestinal
flora, but we still know very little about how we can control the
intestinal flora in the treatment of diseases. This is where synthetic
mucins could open up new treatment options', says Associate Professor
Yoshiki Narimatsu, another of the lead authors of the study.

'Ultimately, one can imagine using mucins as a pre-biotic material,
that is, as molecules that help the good bacteria in the body', says
Yoshiki Narimatsu.

With artificial mucus, it will also be possible to alleviate infections
in the body. Mucus in saliva flushes out bacteria and cleans the oral
cavity, and mucus constantly runs down over our eyes and keeps them clean.

'We imagine that instead of using antibiotics, you might produce for
example eye drops with the mucin that normally removes the bacteria in the treatment of eye infections. In concrete terms, this means that mucin can dissolve the so- called biofilm of bacteria, which is often pathogenic',
says Yoshiki Narimatsu.

Biofilm is a film of bacteria on the surface of a material and is,
among other things, what you can feel on your teeth if it has been a
long time since you last brushed them.

It is not only bacteria that recognise mucins.

'We also show that mucins are very important for the way in which the
common flu virus infects our mucous membranes in competition with
mucins which inhibit the infection and flush out the virus', says
Yoshiki Narimatsu.

Unlike the covid-19 virus, influenza virus binds to a sugar, which is
found on all mucins, and a sugar has already been developed for treatment
of the flu.

'We hope mucins may work even better', says Yoshiki Narimatsu.

========================================================================== Story Source: Materials provided by University_of_Copenhagen_-_The_Faculty_of_Health_and
Medical_Sciences. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Rebecca Nason, Christian Bu"ll, Andriana Konstantinidi, Lingbo
Sun, Zilu
Ye, Adnan Halim, Wenjuan Du, Daniel M. So/rensen, Fabien Durbesson,
Sanae Furukawa, Ulla Mandel, Hiren J. Joshi, Leo Alexander Dworkin,
Lars Hansen, Leonor David, Tina M. Iverson, Barbara A. Bensing,
Paul M.

Sullam, Ajit Varki, Erik de Vries, Cornelis A. M. de Haan, Renaud
Vincentelli, Bernard Henrissat, Sergey Y. Vakhrushev, Henrik
Clausen, Yoshiki Narimatsu. Display of the human mucinome with
defined O-glycans by gene engineered cells. Nature Communications,
2021; 12 (1) DOI: 10.1038/s41467-021-24366-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210707112413.htm

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