To cure food allergies, treat the microbiome

After rising for years, food allergies have now reached near epidemic proportions in western countries. An estimated 8 percent of children are allergic to peanuts, eggs, milk, shellfish, and more.

Immunologists like Prof. Cathryn Nagler are on the case. Nagler, herself allergic to eggs as a child, has studied the human microbiome as the key to curing allergies and other disorders. Her breakthroughs have led to new thinking in the field, and her startup, ClostraBio, is poised to bring new therapeutics to market.

“The microbiome is a fascinating world within a world,” said Nagler, the Bunning Family Professor at the University of Chicago’s Pritzker School of Molecular Engineering (PME). “It’s a new frontier, and we are just beginning to scratch the surface.”

Understanding the bacteria-immune system connection

Her success might be attributed to the fact that she nearly avoided a career in science altogether. In fact, Nagler was almost an artist. As a teenager, she was accepted into the prestigious High School of Art and Design in New York City. At the last minute she decided not to go. Instead, she attended John Dewey high school, and enrolled in a biology course.

“And I’ve been into biology ever since,” she said. “I always saw myself as creative, but I found that discovery in biology was just as creative as painting. And that has been my approach to science ever since. Be creative and don’t be afraid to break new ground. That always keeps it interesting to me.”

Cathryn Nagler
Prof. Cathryn Nagler

As a young researcher at Harvard Medical School in the 1990s, she studied the mechanisms that regulate tolerance to dietary antigens — why certain foods can cause certain reactions within the body. She went on to study inflammatory bowel disease (IBD), which was initially thought to be an autoimmune disorder. But soon researchers began to discover that IBD was an immune response directed against resident bacteria. In fact, they found that a certain kind of bacteria called commensal bacteria interact with the body’s immune system to protect the body and prevent colonization by pathogens. “We were starting to understand that there was this wide world of commensal bacteria in our guts,” Nagler said.

She wondered if food allergies also stemmed from an immune system reaction with commensal bacteria, and in 2004, she and colleagues published one of the first papers showing that the immune system is regulated by microbiota in the gut. More recently, she identified a class of bacteria called Clostridia that produce butyrate, a short-chain fatty acid important in creating a healthy microbial community in the gut. 

“They are called the gut’s peacekeepers,” Nagler said. She found that one species of this bacteria, Anaerostipes caccae, appears to protect against allergic reactions when it is present in the gut.

But introducing these bacteria to the gut takes more than just swallowing a pill: introducing it orally doesn’t cause it to colonize where it’s needed — in the small intestine and colon.

Bringing new therapies to patients

Armed with this knowledge, Nagler teamed up with Prof. Jeffrey Hubbell to develop a polymer system that self-assembles into micelles that can protect and stabilize butyrate and release it slowly into the lower gastrointestinal tract, where bacteria produce butyrate in healthy individuals. This therapy essentially closes the door that allows allergens to be drawn into the body’s circulation.

The company they founded to commercialize this technology, ClostraBio, recently closed on Series A funding that will allow them to do the necessary work to get this therapy to clinical trials, which they hope to do within a year. The company ultimately intends the polymer system to be a platform to which they can attach other metabolites to stabilize the microbiome in new ways.

“Twenty-first century lifestyles have depleted protective bacteria from the resident microbes in our gut,” she said. “This is driving not only food allergies but many other chronic non-communicable diseases, including IBD and even conditions like autism and multiple sclerosis. I want to see this drug in patients. This could be a way to treat allergies and finally give relief to millions of people.”

Once the company launches its therapeutics, Nagler is looking forward to continuing her academic work to study the microbiome further. She originally came to the University of Chicago in 2009 because of its strengths in microbiome research, and she has found the approach of the Pritzker School of Molecular Engineering especially fruitful for her work.

“Everyone here wants to bring their work out into the world and solve problems,” she said. “I’m ready to keep learning new things and continue to be engaged in discovery. I’m just as excited now as I was in graduate school.”