The work of Brigham and Women's Hospital and Boston Children's Hospital in the US highlights the importance of the Clostridiales and the Bacteroidetes bacterial species in suppressing food allergies in the human gut.
“This represents a sea change in our approach to therapeutics for food allergies," says co-senior author Dr Lynn Bry, director of the Massachusetts Host-Microbiome Center at the Brigham.
"We've identified the microbes that are associated with protection and ones that are associated with food allergies in patients.
“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."
Gut role in allergies
A number of food allergies manifest in the first few years of life, suggesting a role of the gut microbiota in its development.
The method of delivery, antibiotic use and breastfeeding, have all been put forward as factors influencing the gut microbiota and influencing the development of atopic disease
A decrease in bacterial diversity and an increased Enterobacteriaceae/Bacteroidaceae ratio in infancy are also linked to food sensitisation, further pointing to the gut microbiota’s role.
The team collected faecal samples every four to six months from 56 infants who developed food allergies, noting differences in the faecal microbiota of 98 infants who did not develop food allergies.
Mice sensitised to eggs received both transplanted samples. The mice receiving microbiota from healthy controls were more protected against egg allergy than those who received microbiota from the infants with food allergies.
Next, the team began analysing differences in the microbial make up of children with and without food allergies.
The team orally administered these protective microbes to mice to see if this approach could prevent the food allergies development.
One group contained five or six bacterial species from the Clostridiales or the Bacteroidetes was found to suppress food allergies in the mouse model.
The team found the group provided full protection for mice giving them a resistance to developing an egg allergy. Further tests with other bacteria species did not result in the same degree of protection.
Identifying protective microbes
“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,” said co-first author Dr Georg Gerber, chief of the division of computational pathology in the department of pathology at the Brigham.
“We were able to narrow in on a specific group of microbes that are associated with a protective effect.
"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."
In the study’s discussion, further examination of the Clostridiales and Bacteroidetes groups found they targeted two immunological pathways stimulating specific immune system T cells.
The team wrote that the bacteria may have induced a relatively tolerant response instead of the more extreme allergic response.
These effects were found both in the pre-clinical models and also found to occur in human infants.
Dr Bry’s team think this approach changes the immune system's wiring in an allergen-independent fashion, with potential to treat food allergies rather than desensitising someone to a specific allergen.
"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,” said Dr Bry.
“With food allergies, this has given us a credible therapeutic that we can now take forward for patient care."
Source: Nature Medicine
Published online: doi.org/10.1038/s41591-019-0461-z
“Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy.”
Authors: Azza Abdel-Gadir et al