Writing in in the Proceedings of the National Academy of Sciences (PNAS), the team of US researchers revealed that the presence of Clostridia, a common class of gut bacteria, may protect against food allergies by encouraging immune responses that prevent food allergens from entering the bloodstream.
The research, which was performed in mice, demonstrated that Clostridia can minimise allergen exposure and prevent sensitisation – a key step in the development of food allergies. The discovery points toward probiotic therapies for this so-far untreatable condition, said the University of Chicago team behind the research.
"We've identified a bacterial population that protects against food allergen sensitisation," said Professor Cathryn Nagler from the University of Chicago. “The first step in getting sensitised 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."
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 sensitisation to food.
Clostridia bacteria are common in humans and represent a clear target for potential therapeutics that prevent or treat food allergies, said Nagler and her team – who 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," she said.
"There are of course no guarantees, but this is absolutely testable as a therapeutic against a disease for which there's nothing.”
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 new-borns (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, the team revealed.
This sensitisation to food allergens could be reversed, however, by reintroducing a mix of Clostridia bacteria back into the mice, they said.
Reintroduction of another major group of intestinal bacteria, Bacteroides, failed to alleviate sensitisation, indicating that Clostridia have a unique, protective role against food allergens, they added.
Closing the door
To identify the protective mechanism behind this finding, Nagler and her team studied cellular and molecular immune responses to bacteria in the gut.
Genetic analysis showed that Clostridia caused innate immune cells to produce high levels of interleukin-22 (IL-22), a signalling molecule known to decrease the permeability of the intestinal lining.
To confirm this theory, 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 again, however, after the mice were given antibodies that blocked the action of IL-22. Taken together, the findings indicate that Clostridia-induced IL-22 prevents allergens from entering the bloodstream, said the team.
"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," commented Nagler. "Our results suggest this could contribute to the increasing susceptibility to food allergies."
Published online ahead of print, doi: 10.1073/pnas.1412008111
“Commensal bacteria protect against food allergen sensitization”
Authors: Andrew T. Stefka, Taylor Feehley, et al