Alimento funcional enriquecido em ácido gama-aminobutírico e probióticos como solução terapêutica inovadora para perturbações de ansiedade

GABAPAID aims to explore new, effective, and non-drug biotherapeutic options for management of anxiety disorders, the most prevalent mental disorders worldwide. In 2019, 301 million people had an anxiety disorder [1]. Building on previous knowledge that both gamma-aminobutyric acid (GABA) and probiotics can elicit mental health benefits [2,3], the GABAPAID proposes incorporating both GABA and probiotics into food matrices as an effective solution for anxiety management. Yet, the main scientific question is: Is it possible to incorporate both GABA and probiotics into food matrices, to develop an innovative and effective strategy for reducing anxiety and improving treatment outcomes? The dual-target hypothesis is supported by the rationale that the intake of incorporated GABA directly relieves stress by interacting with GABA-receptors in the brain and the intake of incorporated probiotics positively modulates the gut microbiota composition and their metabolites, improving anxiety symptoms via gut-brain axis. GABAPAID aims to develop a functional food enriched in both GABA and GABA-producing probiotics, targeting anxiety therapeutically, drawing from the team's expertise in food biotechnology, microbiology and neuroscience. This project is ground-breaking as there are currently no studies on functional foods that incorporate both GABA and probiotics as bioactive ingredients and provide biological validation for anxiolytic effects. To achieve the overall aim GABAPAID has set the following specific objectives (SO): SO1: To promote high GABA yields, by adapting the probiotic fermentation conditions; SO2: To develop and characterise tailor-made delivery systems for enhancing stability of GABA and probiotic strains when subject to in vitro simulated gastrointestinal conditions; SO3: To assess the ability of encapsulated GABA to cross blood-brain barrier and encapsulated probiotics to modulate the gut microbiota composition and metabolites; SO4: To evaluate the in vivo impact of GABA and/or probiotics in a rodent model of anxiety; SO5: To incorporate the developed delivery systems for GABA and probiotics into fruit gum food matrix followed by in-depth characterisation. These SO will be achieved by 5experimental work packages complemented with 2work packages for coordination and management (WP6) and dissemination and communication (WP7): WP1 aims to optimise fermentation conditions for high GABA yield using whey as fermentation substrate, to promote cost-effective and sustainable practices along with assessing the effects of temperature, pH, and medium composition on the process. The use of a co-culture between classical and next generation probiotic strains will be explored as a pioneering technological strategy to enhance GABA yield. WP2 will cover SO2. Encapsulation techniques based on liposomes and spray-drying, respectively will be tested to enhance GABA and probiotics loading capacity and stability throughout gastrointestinal passage. WP3 will use in vitro models - cell lines for blood-brain barrier assays and faecal fermentation for gut microbiota composition/metabolites modulation assays - to cover SO3. WP4 will evaluate the in vivo biological efficacy and safety profile of GABA and/or probiotics in a rodent model of anxiety as proposed in SO4. WP5 will study the formulation, GABA and probiotics incorporation and nutritional, physico-chemical, microbiological and biological characterisation of a fruit gum food matrix as proposed in SO5