by Jenny Ryltenius, Karolinska Institutet

Credit: CC0 Public Domain

When you hear the words mucus and snot, you might think of colds, snails or drooling babies. But the runny, sometimes sticky substance often plays a vital role in our lives, and mucus also has the potential to be a medicine.

From the moist passages of the nose to the winding paths of the intestines, about ten liters of mucus are produced daily. The mucus that most demands our attention is snot—even though we do not notice even a fraction of the approximately two deciliters of snot produced daily.

Pär Stjärne, docent at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, has primarily researched chronic rhinitis (inflammations), in the nose and sinus mucosa.

“The nose has many important tasks that we are not aware of, and the mucous membrane, with its outermost layer of mucus, is essential for all of them,” says Stjärne.

The nose is not the only part of the immune system where it traps particles, viruses and bacteria in the snot. The nasal mucosa also acts as humidifiers and heat exchangers, “optimizing” the air before it reaches the lungs. The mucosa is also essential for our sense of smell. That is just a handful of the nose’s functions.

“The nose is able to manage all its tasks partly because it is lined with mucosa, but also due to its narrow anatomical structure, which creates turbulence. The turbulence in the inhaled air causes particles larger than ten micrometers to be ejected into the mucosa, where cilia transport the particles towards the throat,” says Stjärne.

The functions of the nose are ultimately controlled by the brainstem. Through neurotransmitters, it regulates, among other things, how much or little snot the mucous glands should produce and the blood flow to the nasal mucosa. It is not a myth that one can become addicted to certain nasal sprays—those containing so-called alpha-adrenergic agonists—to reduce swelling and mucus production in the nose.

“If used longer than intended, usually ten days, there is a high risk of developing medication-induced nasal congestion. This is because the number of alpha receptors in the nose decreases. When this happens, the brainstem neurotransmitters become ineffective, and more decongestant nasal spray is needed to avoid congestion,” says Stjärne.

The only cure is to stop spraying and endure a few weeks of congestion until the body’s own system kicks in again.

“This is a very troublesome situation and unfortunately not uncommon. During the weaning process, it tends to be worst at bedtime as the nose swells more. I usually recommend these patients to take a puff of decongestant children’s nasal spray in one nostril at bedtime.”

The color of the snot does not indicate the cause

The idea that the color of the snot can indicate the cause of the infection is a myth, however.

Colds are almost always caused by viruses, which produce a transparent snot as the mucous membrane responds with intense mucus production. This makes us want to sneeze, and our noses run. When you think about it, have you ever had a cold where the snot was colored from the start?

“The change in color of the snot is due to the mucus becoming thicker over time as a result of dead cells such as white blood cells and bacteria. Bacterial growth often occurs later in the cold, when the normally harmless bacteria in the nose have had a chance to grow undisturbed while immune cells have targeted the virus,” says Stjärne.

It becomes, as Stjärne puts it, “an inflammatory soup” that maintains the inflammation and is therefore good to remove with the help of nasal spray or homemade nasal rinse with half a teaspoon of table salt and five deciliters of lukewarm tap water.

“The important thing is to use clean tools in the form of a syringe or nasal cannula. Otherwise, there is a risk that they become breeding grounds for bacteria, prolonging the infection. As for rinsing your nose, even if you have no problems, there is no scientific evidence, but many people find it increases their well-being. I do it myself,” says Stjärne.

When it comes to people with chronic rhinitis, long-term inflammation of the nasal mucous membranes, whether due to an allergy or not, there is much to suggest that nasal rinsing is beneficial for mucus production, according to Stjärne.

Moreover, working in a dry indoor environment with central ventilation, as many do, dries out the mucous membranes, which changes the pH of the nose and causes inflammation.

There are no reliable statistics on how many people suffer from non-allergic rhinitis and chronic nasal congestion, but Stjärne believes it can be classified as a common disease.

“I once conducted a survey in my studies that showed that 25 percent of Stockholmers had nasal congestion lasting more than three months.”

The cause of chronic, non-allergic rhinitis varies, and in some cases, the cause is unknown.

“Many factors can affect the nose, from the air environment and hormonal conditions such as pregnancy to medication. All blood pressure-lowering medications can potentially also affect the nasal mucosa,” says Stjärne.

In response to the question of whether he has any fun facts about snot, he talks about the form snot takes when he operates on chronically inflamed sinuses.

“It is an extremely tough secretion that we pull out, sometimes half a meter outside the body, like a long rubber band,” says Stjärne.

Protecting the intestinal mucosa

If the mucosa in the nose is the body’s first line of defense, the intestinal mucosa could be described as the second. In addition to handling the snot we swallow, it must interact with everything we consciously put in our mouths. Charlotte Hedin, gastroenterologist and researcher at the Gastrointestinal Centre at Karolinska University Hospital and Karolinska Institutet, has spent many years studying the intestinal mucosa in people with inflammatory bowel disease (IBD).

“If the villi (tiny finger-like projections) are taken into account, the intestinal mucosa is the largest surface in the human body that interacts with the outside world. No other part of the body has the same interaction with our environment,” says Hedin.

Just like the nose, the production of mucus is a complex process regulated by several factors, including hormones and immune cells. A major difference, however, is that the mucus and the environment in the intestines are affected by the food we eat. A current research area is to find out how the mucosa is affected by today’s modern ultra-processed foods.

“It has been observed that chemicals such as emulsifiers and preservatives can make the mucus layer in the intestines thinner, making the intestinal barrier more permeable and potentially increasing the risk of inflammation,” says Hedin.

The intestinal mucosa is also unique compared to other mucous membranes in the body because it is incredibly dynamic. This allows it to absorb nutrients from food while keeping out disease-causing microorganisms at the same time. However, sometimes the intestinal mucosa fails in its task, such as when we get food poisoning.

“What happens during such an intestinal infection is that the mucosa is damaged or thinned out. It can even disappear completely. For healthy individuals, the mucosa repairs itself very quickly.

However, this is not the case for the patients on whom Hedin focuses her research—those with IBD, where Crohn’s disease and ulcerative colitis are the most common diagnoses. Her major research questions are to understand how inflammation arises and how to promote mucosal healing.

“The problem with current immunosuppressive treatment is that it does not help everyone with IBD and also that it causes side effects. We really need to find alternatives, and we can do that if we understand why some respond to treatment and heal, and others do not,” she says.

A large study is currently underway where Hedin and her colleagues have collected samples from the intestinal mucosa of IBD patients when it is most severely inflamed. They have then followed up with new samples at various times after the patients have received treatment.

“Some patients get a great effect from immunosuppressive drugs while others are not helped at all. It will be very interesting to compare these samples and see what differs between them.

The analyses will be carried out next year and hopefully, it will provide answers as to which molecules or chemicals are activated during healing.

“The dream is to find a drug that can promote the healing process without suppressing the immune system. That would really be a long-awaited complement to current treatment,” says Hedin.

Cow mucus can prevent transmission of viruses

We have now established that mucus plays a crucial role in our bodies. But the benefits of mucus extend far beyond its natural functions in our bodies. Hongji Yan, a researcher at Uppsala University and affiliated with AIMES at Karolinska Institutet, leads the work on exploring the potential of mucin, the main non-water-based component of natural mucus.

Using mucin from cows, his research team has managed to recreate mucus-like gels.

“Our gels are versatile and can be customized for different biomedical applications as they can appear in both solid and liquid form,” says Yan.

The ability of mucus to take different forms is crucial. As a solid, it can trap viruses and prevent their movement towards the epithelial cells under the mucosa. In liquid form, it can remove virus particles that have reached the epithelium.

One of the gels he has developed will hopefully be able to prevent the transmission of HIV and herpes. Laboratory tests on different cell types have shown promising results; the gel prevented HIV infection in 70% of cases and herpes transmission in 80% of cases.

“A major advantage is that this gel can be used without the risk of developing antimicrobial resistance, which is a problem with antiviral drugs. We hope to test the infection protection in animal studies in two to three years,” says Yan.

In addition to protection against sexually transmitted viral infections, Yan believes that these gels could also protect against bacterial infections such as gonorrhea and chlamydia. His research group has also developed mucin-based gels that remain stable in the body and can function as implants.

“The gels can be injected into the body where they then solidify. They can also be molded in the desired way before implantation,” he explains.

Studies on mice suggest that these gels could be useful in herniated disk surgery to protect intervertebral disks from post-operative inflammation.

“In our studies, we have seen that a simple injection at the surgical site can protect both the nucleus and the vertebral body from further degeneration,” says Yan.

Another potential application is transplant surgery. Yan and his colleagues are currently investigating the possibility of preventing the rejection of insulin-producing pancreatic cells after transplantation to people with type 1 diabetes.

“We are trying to create a gel that can be used as an immunoprotective coating around these cell islets when they are injected into the body. The gel should protect the cells from being attacked by the immune system while not preventing them from releasing insulin once they are transplanted,” says Yan.

If he is allowed to make a prediction, mucus-based treatments and medicines will play a significant role in the future.

“Nature provides us with invaluable insights for the design of biomaterials. Right now, we are in an exciting time where we are learning to replicate and customize the properties of gels with mucins for various medical applications,” he says.

Provided by Karolinska Institutet

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