Can gut bacteria stop peanut allergies?

"There are of course no guarantees, but this is absolutely testable as a therapeutic against a disease for which there's nothing. As a mom, I can imagine how frightening it must be to worry every time your child takes a bite of food," says Cathryn Nagler. (Credit: iStockphoto)

A common class of gut microbe called Clostridia appears to prevent mice from becoming sensitized to peanuts—a key step in the development of food allergies.

Although scientists don’t know what causes food allergies, studies have hinted that modern hygienic or dietary practices may play a role by disturbing the body’s natural bacterial composition.

In recent years, food allergy rates among children have risen sharply—increasing approximately 50 percent between 1997 and 2011—and studies have shown a correlation to antibiotic and antimicrobial use.

“Environmental stimuli such as antibiotic overuse, high-fat diets, caesarean birth, removal of common pathogens, and even formula feeding have affected the microbiota with which we’ve co-evolved,” says study senior author Cathryn Nagler, a professor at the University of Chicago. “Our results suggest this could contribute to the increasing susceptibility to food allergies.”

Testing allergies

To test how gut bacteria affect food allergies, Nagler and her team investigated the response to food allergens in mice. They exposed germ-free mice (born and raised in sterile conditions to have no resident microorganisms) and mice treated with antibiotics as newborns (which significantly reduces gut bacteria) to peanut allergens.

Both groups of mice displayed a strong immunological response, producing significantly higher levels of antibodies against peanut allergens than mice with normal gut bacteria.

This sensitization to food allergens could be reversed, however, by reintroducing a mix of Clostridia bacteria back into the mice. The study appears in the Proceedings of the National Academy of Sciences.

Reintroduction of another major group of intestinal bacteria, Bacteroides, failed to alleviate sensitization, indicating that Clostridia have a unique, protective role against food allergens.

Protection test

To identify this protective mechanism, the team studied cellular and molecular immune responses to bacteria in the gut. Genetic analysis revealed that Clostridia caused innate immune cells to produce high levels of interleukin-22 (IL-22), a signaling molecule known to decrease the permeability of the intestinal lining.

Antibiotic-treated mice were either given IL-22 or were colonized with Clostridia.

When exposed to peanut allergens, mice in both conditions showed reduced allergen levels in their blood, compared to controls. Allergen levels significantly increased, however, after the mice were given antibodies that neutralized IL-22, indicating that Clostridia-induced IL-22 prevents allergens from entering the bloodstream.

“We’ve identified a bacterial population that protects against food allergen sensitization,” Nagler says. “The first step in getting sensitized to a food allergen is for it to get into your blood and be presented to your immune system. The presence of these bacteria regulates that process.”

She cautions, however, that these findings likely apply at a population level, and that the cause-and-effect relationship in individuals requires further study.

Therapeutic approach

While complex and largely undetermined factors such as genetics greatly affect whether individuals develop food allergies and how they manifest, the identification of a bacteria-induced barrier-protective response represents a new paradigm for preventing sensitization to food.

Clostridia bacteria are common in humans and represent a clear target for potential therapeutics that prevent or treat food allergies. Nagler and her team are working to develop and test compositions that could be used for probiotic therapy and have filed a provisional patent.

“It’s exciting because we know what the bacteria are; we have a way to intervene,” Nagler says.

“There are of course no guarantees, but this is absolutely testable as a therapeutic against a disease for which there’s nothing. As a mom, I can imagine how frightening it must be to worry every time your child takes a bite of food.”

The Food Allergy Research & Education and the University of Chicago Digestive Diseases Research Core Center supported the study.

Source: University of Chicago