The impact of high‐IgE levels on metabolome and microbiome in experimental allergic enteritis

Background The pathological mechanism of the gastrointestinal forms of food allergies is less understood in comparison to other clinical phenotypes, such as asthma and anaphylaxis Importantly, high‐IgE levels are a poor prognostic factor in gastrointestinal allergies. Methods This study investigated how high‐IgE levels influence the development of intestinal inflammation and the metabolome in allergic enteritis (AE), using IgE knock‐in (IgEki) mice expressing high levels of IgE. In addition, correlation of the altered metabolome with gut microbiome was analysed. Results Ovalbumin‐sensitized and egg‐white diet‐fed (OVA/EW) BALB/c WT mice developed moderate AE, whereas OVA/EW IgEki mice induced more aggravated intestinal inflammation with enhanced eosinophil accumulation. Untargeted metabolomics detected the increased levels of N‐tau‐methylhistamine and 2,3‐butanediol, and reduced levels of butyric acid in faeces and/or sera of OVA/EW IgEki mice, which was accompanied with reduced Clostridium and increased Lactobacillus at the genus level. Non‐sensitized and egg‐white diet‐fed (NC/EW) WT mice did not exhibit any signs of AE, whereas NC/EW IgEki mice developed marginal degrees of AE. Compared to NC/EW WT mice, enhanced levels of lysophospholipids, sphinganine and sphingosine were detected in serum and faecal samples of NC/EW IgEki mice. In addition, several associations of altered metabolome with gut microbiome—for example Akkermansia with lysophosphatidylserine—were detected. Conclusions Our results suggest that high‐IgE levels alter intestinal and systemic levels of endogenous and microbiota‐associated metabolites in experimental AE. This study contributes to deepening the knowledge of molecular mechanisms for the development of AE and provides clues to advance diagnostic and therapeutic strategies of allergic diseases. Distinctive metabolome and microbiome signatures were detected among different degrees of AE in WT mice and IgEki mice expressing high levels of IgE. IgEki mice exacerbated AE development with altered levels of lipids including sphingolipids, glycerophospholipids and fatty acids and histamine derivative. The exacerbated AE was accompanied with reduced Clostridium and increased Lactobacillus. These findings contribute to establishing AE diagnostics and therapies. Abbreviations: AE, allergic enteritis; g, genus; Ig, immunoglobulin; IgEki, IgE knock‐in; ph, phylum; WT, wild type.