A new study identified the species of bacteria in the human infant gut that protect against food allergies. A resulting oral therapy in mice has replenished the “good” bacteria, prevented food allergies from forming and even suppressed some pre-existing diseases. Contrary to the current therapies, it has the potential to treat food allergies at a much broader scope.
In the US, one in every 13 children has a food allergy and every 3 minutes, a food allergy reaction sends someone to the emergency room. The eight most common food allergens are milk, egg, peanut, tree nuts, soy, wheat, fish and shellfish. The only way to prevent a reaction is to completely avoid the food to which a person is allergic. It is a very hard task in the world of processed food and modern consumer habits. We rarely cook everything from scratch and control every ingredient in our meals.
Recent findings about the microbiome, microorganisms that live in the body, have suggested that altered gut microbiomes may play a big role in the development of food allergies. Researchers from Brigham and Women’s Hospital and Boston Children’s Hospital have discovered that giving an enriched oral formulation of five or six species of bacteria found in the human gut protected against food allergies. In preclinical studies using a mouse model, the team even managed to reverse certain pre-existing diseases by reinforcing tolerance to food allergens. Their promising progress and findings were published in Nature Medicine.
“This represents a sea change in our approach to therapeutics for food allergies,” co-senior author Lynn Bry, director of the Massachusetts Host-Microbiome Center at the Brigham, said in Press Release.
Exhaustive studies were conducted in humans and in preclinical models to understand the key bacterial species involved in food allergies. The team repeatedly collected faecal samples from 56 infants who developed food allergies and 98 infants who did not develop food allergies. Microbiota of the two groups had many differences.
Additionally, faecal microbiota samples from infants with or without food allergies were transplanted into mice who were sensitized to eggs. Mice who received microbiota from healthy controls were more protected against egg allergy than those who received microbiota from the infants with food allergies.
“We’ve identified the microbes that are associated with protection and ones that are associated with food allergies in patients, said Bry. If we administer defined consortia representing the protective microbes as a therapeutic, not only can we prevent food allergies from happening, but we can reverse existing food allergies in preclinical models. With these microbes, we are resetting the immune system.”
The researchers used computational approaches to compare the microbes of children with food allergies to those without allergies. After identifying the protective microbes, researchers orally administered them to mice and tested if they can prevent the development of food allergies.
“It’s very complicated to look at all of the microbes in the gut and make sense of what they may be doing in food allergy, but by using computational approaches, we were able to narrow in on a specific group of microbes that are associated with a protective effect,” said co-first author Georg Gerber, co-director of the Massachusetts Host-Microbiome Center and chief of the Division of Computational Pathology in the Department of Pathology at the Brigham.
Their team has developed two consortia of bacteria that were protective. Each consortium consisted of five or six species of bacteria derived from the human gut that belong to species within the Clostridiales or the Bacteroidetes. These were able to suppress food allergies in the mouse model and keep mice resistant to egg allergy.
“Being able to drill down from hundreds of microbial species to just five or six or so has implications for therapeutics and, from a basic science perspective, means that we can start to figure out how these specific bacteria are conferring protection, said Gerber.”
The team also monitored immunological changes in human infants and mice to gain knowledge on how the bacteria species might be influencing food allergy susceptibility. Clostridiales and Bacteroidetes consortia targeted two immunological pathways and stimulated regulatory T cells. These cells are modulators of the immune system and can promote tolerant responses instead of allergic responses. Same results were found in the pre-clinical models and human infants.
Oral immunotherapy is a common strategy to increase the threshold for triggering an allergic reaction. Allergic individuals get small but increasing amounts of a food allergen and so get desensitized to a specific allergen. On the other hand, the bacteriotherapy changes the immune system’s wiring in an allergen-independent way. Therefore it has the potential to treat food allergies much more broadly.
“When you can get down to a mechanistic understanding of what microbes, microbial products, and targets on the patient side are involved, not only are you doing great science, but it also opens up the opportunity for finding a better therapeutic and a better diagnostic approach to disease. With food allergies, this has given us a credible therapeutic that we can now take forward for patient care,” said Bry.
Bry and Gerber are founders and have equity in ConsortiaTX. The company is developing a live human biotherapeutic product (CTX-944). At the moment, they are preparing for a Phase 1b trial in pediatric food allergy, followed by an expansion into additional allergic diseases.
Learn what happens during an allergic reaction in the video below:
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By Andreja Gregoric, MSc