Most people do not associate mucus with health. The slightly slimy substance that coats the inner surfaces of the nose, lungs and intestines has incredible protective functions, including against infections. Researchers have succeeded in producing synthetic mucus with the same patterns of O-glycan molecules as those in the human body. The new method not only makes it easier to study the interaction between bacteria and mucus but may also help to develop completely new types of medicine.
We swallow more than a litre of mucus through saliva per day. The mucus in saliva flushes out bacteria and cleanses the oral cavity. The mucus mixes with a lot more from the stomach on its way into the intestines. Some people may find this description somewhat overwhelming, but the mucus acts like a giant fishing net that keeps track of all the bacteria and feeds our gut microbiome, which is absolutely essential for determining whether we are healthy or ill. Researchers have come a big step closer to being able to understand how this takes place.
“Mucus comprises mostly mucins, a large family of O-glycosylated proteins. In our study, we developed a method to mimic the distinct patterns of O-glycan structures in the mucins that the bacteria recognize. This means that we are now beginning to understand the important information contained in human mucus and can start producing synthetically with the appropriate O-glycans added. We hope over time that we can create new medicine to mimic the protective effect of mucus,” explains Yoshiki Narimatsu, Associate Professor, Copenhagen Center for Glycomics, University of Copenhagen.
Identifying things for the first time
In recent years, it has become increasingly clear that humans live in close symbiosis with the microorganisms present on the surfaces of our body and especially in the gut. Here, the O-glycan-coated proteins called mucins constitute– both a primary barrier and an ecological niche for the microorganisms of the human microbiome. Without them, pathogenic microorganisms can take over the natural bacterial flora and thus make us sick.
“Mucins are primarily defined by a series of tandem repeated peptide sequences with O-glycans. We therefore developed a series of cells that can produce smaller parts of mucins with different O-glycan molecules,” says Yoshiki Narimatsu.
The researchers thus created a library containing the essential sequences to which bacteria and other microorganisms bind, and by coating surfaces with them, they can now study how bacteria and other microorganisms interact with them.
“The new system now enables us to understand interactions in the gut and other places for the first time. We still know very little about how to manage the gut flora to promote health and treat disease, and the synthetic mucins can open up new treatment options. We recently showed that these mucins also interact with the host immune system and plays a central role in dampening immunity to friendly bacteria,” explains Yoshiki Narimatsu.
Barrier to the outside world
The researchers are initially interested in the mucus in the gut. Medicine may not be as effective if it needs to be eaten and absorbed by the gut. So when medicine is designed as a pill to be swallowed, it may not actually arrive at the target.
“Medicine as a pill has many obstacles on its way through the digestive system and must have time to be dissolved and distributed in the body. With the new system, we hope to find more candidates like X409, so that we can mimic the bacteria’s ability to attach to the intestinal mucus and thus design oral medicine to attach to the mucus and make it more effective,” says Yoshiki Narimatsu.
The researchers hope that the new synthetic mucus eventually may not only help to understand the incredibly many ways mucus benefits our health – in our gut flora and on all internal surfaces in our body in which the mucus layer feeds bacteria. The mucus also acts as a barrier to the outside world, helping to protect us against infectious diseases.
“The O-glycans in the mucus are crucial, and now we can custom design them. Ultimately, one can imagine using mucins as a prebiotic material to help to feed the good bacteria in the body and hinder those that cause disease. Mucus, for example, also constantly bathes and cleanses our eyes, so we hope that, instead of using antibiotics, an eye drop with synthetic mucin could be used to treat eye infections,” concludes Yoshiki Narimatsu.