Metabolomics in the study of allergic enteritis

ZUBELDIA-VARELA EV; BLANCO F; BARKER-TEJEDA TC; ROJO D; VILLASEÑOR A; LAIÑO J; YU P; PEREZ-GORDO M; VIETHS S; BARBAS C; BARBER D; TODA M

Congreso; European Academy of Allergy and Clinical Immunology Digital Congress; 2020

European Academy of Allergy and Clinical Immunology

Background : Allergic enteritis (AE) is a food allergy phenotype observed mainly in children which often have an increase in IgE levels during the course of the pathology. So far, the pathological mechanism of AE and the role of IgE in its exacerbation are not well understood. A possible cause of AE is the disturbance of the microbial ecosystem of the digestive tract; thus, the study of metabolic changes in a murine model of AE by metabolomics is an interesting approach. Therefore, the aim of this work is to study the role of IgE in the development of AE by the obtention of faeces and serum profiles of an animal model by three analytical techniques: Gas Chromatography, Liquid Chromatography and Capillary Electrophoresis, all coupled to Mass Spectrometry. Method : To induce AE, wild type (WT) mice and IgE knock- in (IgEki) mice, which express IgE instead of IgG1, were sensitized with ovalbumin and fed with egg white (EW) diet. As controls, these two mouse strains received an EW diet without sensitization. Serum and faeces samples were used for metabolomic analysis. The three analytical techniques followed an untargeted approach. The raw data obtained were treated using specific software and quality assurance filters. Results : The metabolic profiles showed 2977 metabolic signals in faeces and 2012 in serum. Importantly, after Kruskal- Wallis test, approximately six times more significant metabolites were found in faeces (2330) than in serum (370). Results after Mann-Whitney unpaired test showed differences for all the comparisons between the four groups. Regarding to metabolites in faeces, we observed (i) a clear reduction of several amino acids and organonitrogen compounds in IgEki groups compared to WT groups and (ii) an increase in OVA- sensitized mice compared to non- sensitized controls. Shortchain fatty acids (e.g. butanoic and valeric acids) involved in the maintenance of intestinal homeostasis, were reduced in OVA- sensitized IgEki mice compared to their non- sensitized control. Other metabolic changes in both faeces and serum included increased levels of lysophospholipids in non- sensitized IgEki mice compared with nonsensitized WT mice. Finally, a reduction in some carbohydrates and Krebs cycle metabolites in IgEki mice were observed. Conclusion : High IgE levels may induce gut dysbiosis and disruption of intestinal homeostasis. Moreover, an alteration in energy metabolism and in metabolites related to allergic inflammation takes place. Therefore, IgE may play a role in the development of enteritis.