Integrated Metabolomic and Gut Microbiome Profiles Reveal Postmortem Biomarkers of Fatal Anaphylaxis

The incidence of fatal anaphylaxis is increasing, but there is still no recognized “golden standard” for forensic diagnosis. Due to its non-specific symptoms, especially cardiovascular symptoms without cutaneous changes, it can easily be misdiagnosed as acute myocardial infarction. Here, we established rat models (n = 12) of fatal anaphylaxis (FA), acute myocardial infarction (AMI), and coronary atherosclerosis with anaphylaxis (CAA). The untargeted metabolomics of plasma and 16S rRNA sequencing of fecal matter was performed, and a random forest was used to identify potential biomarkers. Three metabolites (tryptophan, trans-3-indole acrylic acid, and imidazole acetic acid) and three microbial genera (g_Prevotellaceae_Ga6A1_group, g_UCG_008, and g_Eubacterium_hallii_group) were identified as potential biomarkers for distinguishing anaphylaxis and non-anaphylaxis. The classification model of plasma metabolites showed a much better discriminatory performance than that of microbial genus, serum IgE, and tryptase. The performance of the microbial genera was superior to the serum IgE but inferior to the serum tryptase. Forensic samples of fatal anaphylaxis and non-anaphylaxis deaths (n = 12) were collected for untargeted metabolomics detection. The results showed that among the three identified metabolic biomarkers, tryptophan has better stability in cadaveric blood samples. Its diagnostic performance (AUC = 87.1528) was superior to serum IgE and tryptase, making it more suitable as a postmortem biomarker of fatal anaphylaxis.