Project description
Gut microbiome for neurodegenerative diseases
Neurodegenerative diseases (NDDs) remain difficult to diagnose and treat because current approaches largely rely on correlative biomarkers. Predictive, mechanism-guided diagnostics and interventions have the potential to transform NDD treatment. With support from the Marie Skłodowska-Curie Actions programme, the GUT-4D project integrates multi-omics data and machine-learning approaches to develop clinically validated stool-based diagnostic panels. It investigates causal gut-brain and gut-immune mechanisms through deeply phenotyped patient cohorts and experimental models, while also identifying environmental and microbial drivers of dysbiosis via exposome-wide analyses. Finally, it translates these findings into microbiota-targeted interventions, including prebiotics, probiotics, synbiotics, and postbiotics, validated in experimental systems. Overall, GUT-4D seeks to shift neurodegenerative disease care from correlative observations to predictive, mechanism-driven diagnostics and therapies.
Objective
GUT-4D tackles a pivotal frontier in biomedicine: leveraging the gut microbiome to transform the diagnosis, mechanistic understanding, and treatment of neurodegenerative diseases (NDDs) including Parkinson’s, Alzheimer’s, frontotemporal dementia, and amyotrophic lateral sclerosis. The project unites four interconnected research pillars, stool-based diagnostics, gut–disease mechanistic links, dysbiosis drivers, and microbiota-improving interventions, within a rigorously standardized clinical framework for sample and data management. First, GUT-4D will deliver clinically translatable, stool-based biomarker panels by integrating metagenomics, metaproteomics, metabolomics, and host markers with multi-class machine-learning models, overcoming the limitations of single-disease, binary classifiers and advancing omics diagnostics toward validated, assay-ready tools. Second, it will dissect causal gut–brain and gut–immune pathways by combining deeply phenotyped patient cohorts with ex vivo and in vitro mechanistic experiments, mapping microbial metabolites and host proteins, to reveal disease-specific triggers. Third, the project pioneers an exposome–microbiome pipeline that detects exogenous compounds and microbial products directly in fecal samples and applies Exposome-Wide Association analyses, followed by rapid ex vivo functional testing and targeted cellular assays, to build a Modifiable Driver Atlas of actionable dysbiosis factors. Finally, GUT-4D translates insights into therapeutic strategies with pre/pro/synbiotics, postbiotics, and other ecosystem “repair” approaches validated on adaptive ex vivo platforms. By integrating microbiology, clinical medicine, data science, and environmental health, GUT-4D provides a four-dimensional, bench-to-bedside program poised to shift NDD care from correlative observations to predictive, mechanism-guided diagnostics and interventions, strengthening Europe’s capacity for next-generation, microbiome-enabled healthcare.
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Keywords
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-SE - HORIZON TMA MSCA Staff Exchanges
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Call for proposal
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(opens in new window) HORIZON-MSCA-2025-SE-01
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13100 Vercelli
Italy
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