Elucidating the effects of gut microbiota-derived metabolites in iPSC-derived co-cultures from ADHD patients

ongoing

The pathophysiology of the most frequent neurodevelopmental disorder in the world, Attention Deficit Hyperactivity Disorder (ADHD), is influenced by the interaction of genetic and environmental risk factors. Studies have been indicating the association between ADHD and changes in the microbiota-gut-brain axis (MGBA), which may cause neuroinflammation, and subsequent microglial activation, secretion of cytokines and oxidative stress in the central nervous system. However, the precise mechanisms remain elusive and choosing a feasible individual-representative model to study pathomechanisms is challenging. ELEGANCE (“ELucidating the Effects of Gut microbiota-derived metAbolites iN iPSC-derived co-Cultures from ADHD patiEnts”) aims to investigate possible neuroprotective and neurotoxic properties of gut microbiota metabolites in induced pluripotent stem cell (iPSCs)-derived microglia and dopaminergic neurons from ADHD individuals in co-culture. Neuroinflammatory, oxidative stress and metabolic markers will be measured in different contexts (baseline and after treatment with potentially detrimental microbiota metabolites). Potential restoration effects by gut microbiota derived metabolites in compromised phenotypes will be also explored. These findings will elucidate interaction of microglia and dopaminergic neurons and gut microbiota derived metabolites in ADHD and thereby lead to promising novel drug targets. This fellowship will foster collaboration between world leading institutions and top-notch scientists, introducing me to the microbiome field, enhancing my expertise in transcriptomics, bioinformatics, networking and leadership. The project could significantly impact the knowledge about ADHD pathomechanisms and open doors for new treatment and dietary approaches targeting the MGBA.