Microbial metabolism of food allergens determines the severity of IgE-mediated anaphylaxis

Anaphylaxis is an acute, potentially life-threatening reaction, often triggered by foods and largely mediated by IgE. A critically important aspect of anaphylaxis pertains to the factors that modulate its severity. The human microbiota is known to influence oral tolerance, but the microbial mechanisms directly involved in IgE-mediated anaphylaxis remain unknown. Here, we demonstrate that human saliva harbors peanut-degrading bacteria that metabolize immunodominant allergens (Ara h 1 and Ara h 2) and alter IgE binding. Additionally, we provide in vivo evidence showing that oral bacteria metabolize peanut allergens, influencing systemic allergen exposure and the severity of anaphylaxis. Finally, in a clinical study, we observe that common peanut-degrading bacteria, such as Rothia, from the oral cavity, are more abundant in peanut-allergic patients who exhibit better tolerance to allergen exposure. Altogether, these results demonstrate the role of the human microbiota in modulating IgE-mediated reactions through allergen metabolism. These findings reveal a novel microbial mechanism with potential to prevent, or reduce, the severity of IgE-mediated anaphylaxis.