Barbas Arribas, CoralBlanco-Pérez, FrankBarber Hernández, DomingoBarker Tejada, Tomás CliveVillaseñor Solis, Alma CristinaZubeldia Varela, ElisaIslam, JahidulGonzález-Menéndez, IreneQintanilla-Martínez, LeticiaKrause, MarenSteigerwald, HannaMartella, ManuelaQuintanilla-Martinez, LeticiaYu, PhilippVieths, StefanNochi, TomonoriToda, MasakoRojo Blanco, DavidPérez Gordo, MarinaGrupo: Enfermedades inmunológicas inflamatorias (ALLERGY)Universidad San Pablo-CEU. Facultad de Medicina.2024-07-312024-07-312024-06-23Zubeldia-Varela E, Blanco-Pérez F, Barker-Tejeda TC, et al. The impact of high-IgE levels on metabolome and microbiome in experimental allergic enteritis. Allergy. 2024; 00: 1-18. doi:10.1111/all.162021398-9995http://hdl.handle.net/10637/16084Background: The pathological mechanism of the gastrointestinal forms of food aller-gies is less understood in comparison to other clinical phenotypes, such as asthmaand anaphylaxis Importantly, high-IgE levels are a poor prognostic factor in gastroin-testinal allergies.Methods: This study investigated how high-IgE levels influence the development ofintestinal 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 me-tabolome with gut microbiome was analysed.Results: Ovalbumin-sensitized and egg-white diet-fed (OVA/EW) BALB/c WT micedeveloped moderate AE, whereas OVA/EW IgEki mice induced more aggravated in-testinal inflammation with enhanced eosinophil accumulation. Untargeted metabo-lomics 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, whichwas 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 anysigns of AE, whereas NC/EW IgEki mice developed marginal degrees of AE. Comparedto NC/EW WT mice, enhanced levels of lysophospholipids, sphinganine and sphin-gosine were detected in serum and faecal samples of NC/EW IgEki mice. In addi-tion, several associations of altered metabolome with gut microbiome—for exampleAkkermansia with lysophosphatidylserine—were detected.Conclusions: Our results suggest that high-IgE levels alter intestinal and systemic levelsof endogenous and microbiota-associated metabolites in experimental AE. This studycontributes to deepening the knowledge of molecular mechanisms for the developmentof AE and provides clues to advance diagnostic and therapeutic strategies of allergicdiseasesapplication/pdfenopen accessMicrobiomeFood allergyMetabolomicsMurine modelArtículo10.1111/all.16202https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es