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 immunoglobulin (Ig)E. 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 and jejunum harbor peanut (PN)-degrading bacteria that metabolize immunodominant allergens (Ara h 1 and 2), reducing IgE binding and anaphylaxis. Isolated Rothia and Staphylococcus species degraded PN allergens in vitro, generating proteins with reduced IgE binding and limited mast cell activation. Mice colonized with Rothia showed reduced local and systemic Ara h 1 and 2 levels and dampened anaphylaxis upon PN challenge. In clinical studies, common PN-degrading bacteria, including Rothia, are more abundant in PN-allergic patients who exhibit better tolerance to allergen exposure. Altogether, these results demonstrate that human microbiota modulates IgE-mediated reactions to foods through allergen metabolism, highlighting potential avenues to prevent or reduce the severity of IgE-mediated anaphylaxis.