Food allergies are serious medical conditions affecting up to 15 million people in the United States, including one in 13 children, according to the organization Food Allergy Research & Education (FARE). Some states, including Michigan and North Carolina, require schools to be equipped with emergency EpiPens to respond to serious allergies in their students.
In the new study, published in Proceedings of the National Academy of Sciences, a team of researchers from the University of Chicago Medicine and Biological Sciences studied food allergy triggers in mice.
They exposed germ-free mice (born and raised in sterile conditions to have no native gut bacteria) and mice treated with antibiotics as newborns (which significantly reduces gut bacteria) to peanut allergens. Both groups of mice displayed a strong immune system response, producing significantly higher levels of antibodies to fight the peanut allergens than mice with a normal population of gut bacteria.
Clostridia Keeps Allergens from Entering the Bloodstream
The researchers found that this sensitization to food allergens could be reversed by reintroducing a mix of Clostridia bacteria into the mice's guts. Reintroduction of another major group of intestinal bacteria, Bacteroides, failed to alleviate food sensitivities, indicating that Clostridia play a unique, protective role against food allergens.
To identify this protective mechanism, the researchers studied 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. Children with food allergies are know to have greater permeability in their guts when they eat problem foods.
In a second part of the experiment, the antibiotic-treated mice were either given IL-22 or were colonized with Clostridia. When exposed to peanut allergens, mice in both groups 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 food allergens from entering the bloodstream.
New Generation Has More Food Allergies
Senior study author Cathryn R. Nagler, Ph.D., a professor of pathology and medicine, and Bunning Food Allergy professor at the University of Chicago, told Healthline, “We've identified a pathway to allergic sensitization to food that is regulated by bacteria. We know that in just a generation, a change in the prevalence of food allergy and life threatening allergic responses to food has occurred. It’s unlikely that something has changed dramatically in the way we prepare food. It’s more likely that something has been changing in our environment.
"There are many diseases called 'diseases of the western lifestyle,' like diabetes, inflammatory bowel disease, and obesity, that are all increasing along with allergic disease," she added. "All of these have now been linked to the influence of the bacteria that live in our intestines.”
Overuse of antibiotics and diets high in fatty, processed foods have changed the composition of the bacteria in our intestines, and have also contributed to food allergies. "They eat what we eat and they respond and change their populations based on what we eat," said Nagler.
Why are some people allergic to a given food while other people are not? Nagler explained that all the foods we eat have the potential to cause an immune response. Some people are not allergic to food because a specific physiological mechanism shuts off that response. In people who get food allergies, that response is broken, and they start to react strongly to foods that are not harmful.
The IgE Factor
In the study, Nagler said, the researchers were evaluating the IgE response to food allergens. "IgE is the form of antibody that is required for an allergic response. It was already known that to prevent an allergic response to food, to keep our bodies at peace with the foods coming into our bodies every day, we make a regulatory response that is very specific for those food allergens," she said. "[In the case of allergens,] our immune system is recognizing them, but is not making a regulatory response, or a response that maintains homeostasis, which keeps the peace.
"We found that in addition to that response directed against the dietary antigens, there is also a response elicited by and specific for the commensal bacteria (they live with us and don’t cause any harm, but also have some benefit). We have ten to a hundred times more bacteria in our body than the cells. They cover all of our mucosal surfaces, meaning the airways, genitourinary tract, and particularly the intestines," said Nagler.
The researchers found that when they treated mice with antibiotics to deplete the bacteria living in their intestines, the mice's sensitivity to food allergens, or their IgE response, increased. “Then we tried to find out which bacterial population it was, and in a whole series of experiments, we settled on Clostridia, which are oxygen-sensitive bacteria," Nagler said. "They can’t live outside of an environment that is oxygen free. Deep inside your body, deep inside your intestines, there's no oxygen, and that’s where this kind of bacteria live.
"They are always signaling to our bodies, but we’re not usually making a response to them. We found they generate particular signals that promote the production of mucous and natural antibiotics the body makes to reinforce the barrier [of the intestinal lining] and prevent those food allergens from getting past the epithelial barrier and into our blood," said Nagler.
A Pill for Food Allergies?
What impact will this mouse study have on human subjects?
"The exciting implication for consumers is this gives us a way to intervene and see if we can now use modulation of the bacteria in our gut as a way to prevent or treat food allergies," Nagler said. "We could use the Clostridia to develop a novel, new treatment we can give to people with food allergies, or to protect people before they get food allergies, to elicit this barrier protective response. This is a totally new probiotic."
Nagler said that several companies are already working to develop this new probiotic. "In fact," she added, "we are working with one company. Clostridia are very difficult to work with because they can’t be exposed to oxygen. The good thing about them is they form very stable spores that can live under very extreme conditions. We can potentially collect spores of Clostridia and create them as a pill."