Imunomodelação da barreira intestinal alérgica para investigar as interações resultantes de fenómenos de processamento alimentar, digestibilidade, absorção e transporte na mitigação da alergenicidade

Food allergy (FA) is a well-recognised problem of public health, whose relevance has been gaining momentum at global scale, representing a current/very important societal challenge. FA affects up to 10% of world’s population and it is a complex health condition (typically IgE-mediated), often with fatal consequences for the food-allergic individuals, and whose clinical expression is highly dependent on several immunological events and on the triggers (food allergens). Based on the growing existing experience of the research team in structural/immunological characterisation of food allergens, the innovative nature of IMMUNO-GATE regards the exploitation of mechanisms and interactions occurring during the major steps anticipating and elapsing a FA event. A major challenge in FA research concerns the consecutive faith of food allergens as affected by processing treatments down to their interaction with the immune system, passing through the GI digestion and absorption/transport processes. So far, there is no consensus regarding the availability of a gut model that mimics the in vivo condition of an allergic individual. In this sense, IMMUNO-GATE intents to go beyond the state-of the art and bring novel solutions to this problem by addressing the critical points along the processing, digestibility, absorption/transport of food allergens. Special attention will be given to understanding how processed proteins are presented to the immune system and the mechanisms through which they may induce tolerance rather than an allergic response. IMMUNO-GATE is a pioneering and ambitious proposal that aims at filling the GAPS on the impact of allergen interactions on GI digestion and subsequent absorption/transport phenomena, unravelling new ways of modulating dietary components to minimize allergen exposure and the possibility of identifying novel molecules that could be used in potential allergen-specific immunotherapies. Therefore, IMMUNO-GATE objectives will be focused on providing answers to the following queries: (1) what makes a protein into an allergen? • To study the pairs of allergens/non-allergens from the same protein family in order to determine the physicochemical properties related to allergenicity; • To test a specific set of important allergens (tropomyosins/arginine kinases from animals and 2S albumins/nsLTP/globulins from plants) related to the elicitation of mild to severe allergic reactions; (2) how to manipulate processing treatments and food matrix to reduce protein allergenicity? • To assess the effect of treatments enabling protein fragmentation aiming to facilitate its digestion; • To evaluate the impact of lipids/carbohydrates and their allergen-interaction within the context of FA; (3) how to modulate the gut barrier to eliminate food allergic reactions? • To assess gut barrier models that best mimics the in vivo condition of FA; • To advance new strategies to mitigate the allergenic potential of proteins as affected by lipids/carbohydrates during GI digestion, which might involve manipulating the lipidic/sugar composition of different foods or by the use of blocking agents (pharmaceutical drugs) during intestinal absorption; • To provide novel data on how to remove/incorporate different food compounds (lipids/carbohydrates), considering a final application for FA therapy, following the recently proposed strategy for peanut immunotherapy by the administration of defatted encapsulated peanut flour.