Descrizione del progetto
Il ruolo dei metaboliti del microbiota intestinale nell’infiammazione cerebrale
Il microbiota intestinale è noto per la sua importanza fisiologica e le alterazioni della sua composizione sono associate a varie malattie, tra cui la sclerosi multipla (SM). L’interesse del progetto BRAINeSs, finanziato dall’UE, è comprendere il modo in cui i cambiamenti negli acidi grassi a catena corta, i metaboliti chiave del microbiota, possono causare patologie del sistema nervoso centrale. Per raggiungere questo obiettivo, i ricercatori esamineranno il ruolo degli acidi grassi a catena corta nella barriera ematoencefalica, nelle cellule immunitarie, nelle cellule staminali neurali, nei neuroni maturi e nelle cellule gliali. BRAINeSs, grazie a una serie di metodologie d’avanguardia, contribuirà allo sviluppo di nuovi interventi che potrebbero andare oltre la SM e interessare altre malattie neuroinfiammatorie o neurodegenerative.
Obiettivo
The human gut hosts trillions of microbes collectively called the microbiota, which secretes metabolites that have been strictly linked to the regulation of physiological functions. Among them, short-chain fatty acids (SCFAs) play a key role. Many pathologies are associated with microbiota alterations, including multiple sclerosis (MS), a brain autoimmune disease representing a major public health challenge in Western society. Although preliminary studies in mouse models showed that SCFAs have multiple actions, including immunomodulatory function and influencing the differentiation of stem cells, we still miss a comprehensive study that correlates mechanistically how changes in the microbiota, and, as a direct consequence, in SCFAs, favor autoimmunity in the central nervous system (CNS). Thus, in BRAINeSs, we propose to analyze the effect of SCFAs on different components of the CNS, to unravel the complexity of their action. Particularly, we will look at the impact of SCFAs on the integrity of the blood-brain barrier, immune cells, neural stem/precursor cells, mature neurons, and glial cells. BRAINeSs will allow us to broaden the analysis on the impact of SCFAs in MS through a multidisciplinary approach that spans from metabolomics to immunology, neuroscience, and bioinformatics, and takes advantage of cutting-edge methodologies, as single-cell RNA sequencing and human brain organoid culture. Our plan of research could be applied as a model for the study of other neuroinflammatory or neurodegenerative diseases and could lead to a new therapeutic perspective. I will gain new technical and soft skills through advanced training, necessary to reach full independence. BRAINeSs addresses the third UN development goal, “good health and wellbeing”, and strengthen the interest of the EU for microbiota and multiple sclerosis studies. BRAINeSs is compliant with the Work Program of H2020, which lean toward open-access science, and dissemination/public engagement activities.
Campo scientifico
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
- medical and health scienceshealth sciencespublic health
- medical and health sciencesbasic medicineneurologymultiple sclerosis
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesbasic medicineimmunologyautoimmune diseases
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
20132 Milano
Italia