Your microbiome may determine your risk of a severe allergic reaction

The microbiomes in our gut and mouth can determine whether people with peanut allergies develop a life-threatening reaction. This could help explain why some people with allergies have relatively mild reactions, while others develop severe or even life-threatening symptoms.

“The big question arises as to why some patients are more likely to have more severe reactions,” says Rodrigo Jiménez-Saiz of the Autonomous University of Madrid, Spain.

Peanut allergy occurs when the immune system mistakenly identifies proteins in the legume as a threat, causing it to produce excessive amounts of a particular type of antibody. This accelerates inflammation, leading to symptoms such as itching, swelling and vomiting. In extreme cases, exposure to peanuts causes anaphylaxis, a potentially fatal reaction that usually results in difficulty breathing.

Jiménez-Saiz and his colleagues wondered whether the microbes that live on and in us play a role here, given the enormous influence that our body’s different microbiomes have on our immune system.

To find out, they inserted a small amount of peanut into the stomachs of three groups of mice without any allergies. The first group was bred to develop no microbiome (called germ-free mice), while the second had a minimally diverse microbiome and the third had a microbiome typical of a healthy mouse.

Forty minutes later, the team discovered higher levels of two proteins playing a major role in peanut allergy, known as Ara h 1 and Ara h 2, in the small intestines of germ-free mice with minimal microbiome than in those with the most diverse microbiome.

Further analysis revealed that the latter group contained the highest levels of a group of bacteria called Rothiaespecially the tension Rothia R3which participates in the digestion and breakdown of peanuts in the intestine.

To explore whether Rothia R3 influence the risk of anaphylaxis, the researchers induced severe peanut allergies in a distinct group of mice, whose microbiome was not very diverse.

They then implanted Rothia R3 into some of their intestines, before delivering the peanut paste directly into all of the animals’ stomachs. Forty minutes later, all mice had developed anaphylaxis, but the body temperature of those given Rothia R3 had decreased by only 2 percent on average, compared to 3.5 percent for mice that did not receive it. Anaphylaxis usually causes a drop in body temperature, which can lead to hypothermia and organ failure.

THE RothiaThe implanted mice also had about half the levels of an immune molecule called MMCP-1 in their blood, which typically increases during anaphylaxis, compared to control mice. “The results are convincing,” says Mohamed Shamji of Imperial College London. “If a similar immunological change occurred in humans, this would be expected to reduce the severity of anaphylaxis symptoms.”

In another experiment involving 19 people with peanut allergies, the team found that those who tolerated peanuts better had significantly higher levels of health. Rothia bacteria in their saliva than those with more severe allergies. This suggests that the presence of these bacteria in people’s mouths as well as their intestines influences their risk of anaphylaxis.

Rothia Probiotics may one day reduce the severity of anaphylaxis that develops during a peanut allergic reaction, Shamji says. “The need for something like this is enormous,” he says. In particular, this could ease fears about accidental exposure to peanuts and reduce the risk of adverse reactions during oral immunotherapy, which aims to treat allergies by gradually exposing people to increasing doses of an allergen, he says.

The team hopes to demonstrate the potential of such a treatment in a clinical trial by giving people with peanut allergies either Rothia probiotics or a placebo, before exposing them to low levels of peanuts, says Jiménez-Saiz.