Gut Feeling: UF scientists create synthetic mucus to fight IBD

As many as 3 million Americans suffer from inflammatory bowel diseases like ulcerative colitis and Crohn's disease. Luiz Roesch and Brent Sumerlin think synthetic mucus might give them relief.

Doctors typically treat the inflammation in the bowels that can lead to diarrhea, stomach pain, fatigue, nausea and weight loss. But Roesch, a microbiologist, and Sumerlin, a chemist, think their artificial mucus could prevent the problem in the first place. By restoring the gut’s mucus barrier – a protective layer that keeps microbes and toxins away from intestinal cells – the material could help prevent the immune reactions that drive inflammation.

“We want to target the source of the inflammation, which are the bacterial toxins. When we block the toxins, inflammation is reduced,” says Roesch, an associate professor of microbiology and cell science at the UF Institute of Food and Agricultural Sciences.

Roesch also sees a host of other potential uses for synthetic mucins. That includes using them alongside existing IBD treatments to reduce reliance on immunosuppressants. With different chemical compositions, synthetic mucin might also be useful for treating issues in the lungs, mouth and reproductive tract, as well as in veterinary applications.

Making mucin – the main ingredient of mucus – in the lab has plenty of scientific hurdles. In nature, mucin is a long, chain-like protein that is densely decorated with short chains of sugars. Gut mucus also has to be selective, trapping toxins but allowing water, gases and nutrients to pass. For now, there is no synthetic mucus on the commercial market.

Roesch and Sumerlin aimed to duplicate how mucin works in the body. The synthetic mucin closely mimics the function, size and architecture of its natural counterpart.

“We could never really replicate that sort of complexity. Instead, we made polymers that behave like natural mucin,” Sumerlin says.

Artificial mucin represents a potentially significant change in how IBD can be treated, Roesch says. While existing medications focus on calming the body’s immune system after the fact, a robust mucus layer may stop inflammation from happening.

The synthetic mucin has already undergone toxicity and efficacy testing in cells and a trio of tests in mice, Roesch says.  

Roesch’s group dissolved the polymer in water and gave it to mice. It worked immediately: Mice with low levels of natural intestinal mucus showed broad improvements in inflammation and overall gut health. 

Later, mice with colitis – colon inflammation that depletes the mucus barrier – gained weight and recovered from inflammation after the synthetic mucin treatment.

“I don’t think any of us expected it to work on the first try,” Sumerlin says. “It took Luiz being very brave at the beginning and saying, ‘Hey, let’s give this a try.’”

Scientists already knew how to assemble the long chains of atoms used to create polymers. They also know how to create very complex polymers. Doing that together is exceptionally difficult.

Sumerlin found a breakthrough that does both, using light instead of heat to more directly activate and regulate the polymerization process. That, he says, is a “perfect tool” for producing synthetic mucin.

Sumerlin was already working on the improved polymerization techniques when Roesch came along with the idea for a therapeutic use. After being introduced by a former colleague, Roesch reached out to Sumerlin about synthetic mucin. It was a long-held idea for Roesch but he lacked the expertise to produce the material. 

“UF had the perfect combination of factors that allowed this to happen,” Sumerlin says. “The fact that the artificial mucin application came second speaks loudly about the need for basic science research.

The researchers say the synthetic mucin could one day be produced as a powder that can be mixed with water or other liquids and taken regularly to manage IBD symptoms. 

“Hopefully, we can reduce symptoms and keep IBD patients in remission for a longer period of time,” Roesch says.

Further testing in humans and FDA approval will be required. The team hopes to start an initial-phase human clinical trial focusing on safety and dosages later this year.  The synthetic mucin is mass-producible at room temperature, which makes the process much simpler.

“The symptoms of IBD can be incredibly disruptive. Many people have just become accustomed to living with that,” Sumerlin says. “If we can help them live something that resembles more of a normal life, that would be our ultimate goal.”