Integrated gut metabolome and microbiome fingerprinting reveals that dysbiosis precedes allergic inflammation in IgE-mediated pediatric cow’s milk allergy

Abstract

Understanding the underlying mechanisms behind IgE-mediated cow’s milk allergy (IgE-CMA) is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies. Here, we report data on the gut microbiome, metabolome, and lipidome of 81 children affected by food allergies, including CMA and healthy controls. Moreover, we developed a mouse model that mimicked IgE CMA best, BALB/c mice sensitized with ß-lactoglobulin using cholera toxin. During sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid and tryptophan metabolites, that preceded allergic inflammation, while this inflammation was reflected in a disturbed sphingomyelin and histamine metabolism. We endorsed the microbial origin of these metabolites by in vitro colonic digestions and confirmed the microbial dysbiosis in our patient cohort, which was accompanied by metabolic signatures of low-grade inflammation. Our results suggest that gut dysbiosis precedes allergic inflammation, opening new opportunities for future prevention and treatment strategies. Trial: NCT04249973.

Metabolomic pathways in food allergy

“…Therefore, it is necessary to compare metabolites using samples collected from study groups, considering factors such as age, types or number of FA, dietary restrictions, and diagnostic methods. Recently, a study addressing these limitations by considering them in the study design has been reported 90 . The study focused on children with milk allergy who were placed on dietary restrictions, comparing the metabolites in the subacute or chronic state, while metabolic analysis related to acute allergic reactions associated with sensitization and allergic inflammation was conducted through the animal model.…”

“…Recently, a study addressing these limitations by considering them in the study design has been reported. 90 The study focused on children with milk allergy who were placed on dietary restrictions, comparing the metabolites in the subacute or chronic state, while metabolic analysis related to acute allergic reactions associated with sensitization and allergic inflammation was conducted through the animal model. Finally, although various distinct metabolites have been identified in FA, their specific roles in FA are still relatively poorly understood.…”