Peanut anaphylaxis: microbiota modulates severity
A mechanistic study combining mouse models with two clinical cohorts (n=19, then n=120) shows that oral and gut microbiota break down major peanut allergens and influence the severity of IgE-mediated anaphylaxis. Peanut allergy persists in more than 70% of patients and affects health and daily life, particularly in children.
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Microbial metabolism of allergens modulates anaphylaxis in mice
In mouse models with controlled, minimal or complex microbiota, gut microbiota composition directly determines the ability to break down Ara h 1 and Ara h 2, the major peanut allergens.
Three sensitization protocols were compared1 to establish this link in the development of the allergic response. The first exposed the allergen orally, which is a route that involves gut microbiota from the sensitization phase onward. The second injected the allergen directly into the peritoneum, bypassing the digestive tract and therefore the microbiota. The third passively transferred serum already containing anti-peanut IgE, without an active sensitization step.
During oral sensitization, the group of mice with minimal microbiota, which break down Ara h 1 and Ara h 2 less effectively, developed both more specific IgE and a more severe allergic reaction than mice with complex microbiota. In the case of intraperitoneal sensitization, which bypasses the gut microbiota, mice with minimal microbiota and mice with complex microbiota produced similar IgE levels. However, during the subsequent oral challenge, the allergic reaction in mice with complex microbiota was less severe, demonstrating the direct involvement of the gut microbiota in the allergic reaction.
To confirm the results, serum rich in peanut-specific IgE was injected directly into naïve mice, thus eliminating any active sensitization step. Even in this case, the group of mice with minimal flora reacted more strongly to the oral challenge than mice with complex flora, confirming that the microbiota also influences severity at the time of allergen exposure. Microbiota therefore influences peanut allergy, both through IgE production during oral exposure and, independently, through the number of Ara h 1 and Ara h 2 allergens that actually reach the bloodstream at the time of the challenge.
Can microbiota prevent peanut allergy?
Rothia and Staphylococcus: strain-dependent degradation
In humans, the bacterial genus Rothia accounted for up to 43% of the salivary microbiota in the healthy donors studied. All Rothia strains tested in the study consistently degraded Ara h 1 and Ara h 2 by cleaving the proteins, particularly at epitopes recognized by the IgE of patients with peanut allergy, thereby reducing mast cell activation in functional tests.
Genome sequencing identified candidate proteases, including a subtilisin-like family in Rothia, already known to degrade gluten. The proposed mechanism has not yet been directly demonstrated, as researchers have not deleted the gene to establish its role.
In Staphylococcus, the effect depended on the strain studied, as two different tested strains of S. aureus showed opposite behaviors: one partially broke down Ara h 1, while the other had no detectable effect on either allergen. Serum allergen levels in mice colonized by the latter were higher, and an ex vivo Ussing chamber test confirmed increased allergen passage through the intestinal mucosa.
The authors suggest two possible explanations: partial breakdown that may facilitate the passage of allergen fragments, or impaired intestinal barrier permeability caused by certain Staphylococcus strains, independently of their ability to break down the allergen.
A clinical association to be prospectively confirmed
In 19 patients about to start oral immunotherapy, the peanut allergy tolerance threshold, determined through a controlled food challenge, is associated with a higher abundance of Micrococcales—an order that notably includes Rothia—regardless of specific IgE levels. This association was found in an external cohort of 120 children who underwent double-blind, placebo-controlled food challenges, with the Rothia aeria species being more abundant in non-allergic children and in allergic children with a high peanut tolerance threshold.
This data remains observational and cross-sectional. The authors call for longitudinal monitoring of the oral microbiota during immunotherapy treatment. From a clinical perspective, this research points to the potential for functional characterization of the oral microbiota in food allergy assessment, alongside IgE testing, without replacing established diagnostic tools at this stage.
Microbial metabolism of allergens
Certain microbiotal bacteria* can directly transform the molecular structure of a food allergen, thereby modifying its recognition by the immune system**, regardless of the level of IgE sensitization.
*Microbiotal bacteria (enzymatic breakdown of food proteins) : microorganisms in the oral cavity and intestine that use proteolytic enzymes to break down food proteins resistant to human digestion, including peanut allergens.
**Immune system : all the cells and molecules that protect the body against infections, abnormal cells and foreign substances. In an allergy, IgE and mast cells are involved in recognizing the allergen and triggering the reaction.
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