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

Project description

Unravelling the gut-brain connection in ADHD

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition. Unfortunately, its underlying mechanisms are poorly understood. Recent studies suggest that disruptions in the microbiota-gut–brain axis (MGBA) may contribute to ADHD by triggering neuroinflammation and oxidative stress. Supported by the Marie Skłodowska-Curie Actions programme, the ELEGANCE project investigates how gut microbiota-derived metabolites affect brain cells by using cutting-edge co-cultures of patient-derived microglia and dopaminergic neurons. It will study inflammatory and stress responses and test the potential for microbiota-based restoration. Overall, ELEGANCE aims to identify novel drug targets and pave the way for microbiome-informed therapies and dietary interventions for ADHD.

Objective

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.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 252 728,64
Total cost

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No data

Partners (1)

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