Facultad de Medicina

Background: 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 allergicdiseases

The prevalence and severity of allergic diseases have increased over the last 30 years. Understanding the mechanisms responsible for these diseases is a major challenge in current allergology, as it is crucial for the transition towards precision medicine, which encompasses predictive, preventive, and personalized strategies. The urge to identify predictive biomarkers of allergy at early stages of life is crucial, especially in the context of major allergic diseases such as food allergy and atopic dermatitis. Identifying these biomarkers could enhance our understanding of the immature immune responses, improve allergy handling at early ages and pave the way for preventive and therapeutic approaches. This minireview aims to explore the relevance of three biomarker categories (proteome, microbiome, and metabolome) in early life. First, levels of some proteins emerge as potential indicators of mucosal health and metabolic status in certain allergic diseases. Second, bacterial taxonomy provides insight into the composition of the microbiota through high-throughput sequencing methods. Finally, metabolites, representing the end products of bacterial and host metabolic activity, serve as early indicators of changes in microbiota and host metabolism. This information could help to develop an extensive identification of biomarkers in AD and FA and their potential in translational personalized medicine in early life.