Untargeted metabolomic reveals changes in serum metabolism in peanut allergic mice treated by raw and roasted peanuts

Peanut allergy (PA), which affects an increasing proportion of people, is gaining increasing interests. Clarification of the mechanism underlying PA may aid in the identification of novel biomarkers and strategies for clinical intervention in allergic patients. In this study, raw peanut protein (Raw), roasted peanut protein (Roast), high-molecular-weight protein aggregation from Roast (OH), and the remaining components excluding OH from roasted peanut (OL) were administrated via intraperitoneal injection to challenge BALB/c mice. The allergic response was assessed, and the levels of peanut-specific immunoglobulin E, mouse mast cell protease-Ⅰ, and T-lymphocyte subsets and secreted cytokines were detected. Then, serum untargeted metabolomics was investigated. Results show that Raw induced robust anaphylaxis in mice and up- or down-regulated 269 serum metabolites that mainly affected amino acid metabolism, including tryptophan metabolism, and induced disruption of tricarboxylic acid (TCA) cycle pathway in serum. Roast, OH and OL induced mild anaphylaxis in mice and mainly affected the glycerophospholipid metabolism in serum. Compared with Tris, OH upregulated the glycerophospholipid metabolism pathway in mouse serum, whereas Roast and OL showed the reversed effect. Mice in the Roast, OL, and OH groups all showed upregulated glycerophospholipid metabolism in serum compared with those in the Raw group. Meanwhile, different components of roasted peanut caused various changes in pathways when compared with each other. Compared with mice in the Roast group, those in the OL group displayed downregulated tryptophan and tyrosine metabolism, and those in the OH group showed upregulated glycerophospholipid metabolism and downregulated TCA cycle. The differences in serum metabolic profiles in mice implied that the processing form of allergen that patients are sensitized to and the severity of allergy should be considered in the analysis of serum biomarkers.