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.”
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.