Description du projet
Le rôle des métabolites du microbiote intestinal dans l’inflammation cérébrale
Le microbiote intestinal est connu pour son importance physiologique, et les altérations de sa composition sont associées à plusieurs maladies comme la sclérose en plaques (SP). Le projet BRAINeSs financé par l’UE s’attache à comprendre comment les changements des acides gras à chaîne courte (AGCC), des métabolites clés du microbiote, sont susceptibles de mener à des pathologies du système nerveux central. Pour y parvenir, les chercheurs étudieront le rôle des AGCC au sein de la barrière hématoencéphalique, des cellules immunitaires, des cellules souches neuronales, des neurones matures et des cellules gliales. À l’aide d’une batterie de méthodologies dernier cri, BRAINeSs appuiera le développement de nouvelles interventions susceptibles d’aller au-delà de la SP, profitant potentiellement au traitement d’autres maladies neuro-inflammatoires ou neurodégénératives.
Objectif
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.
Champ scientifique
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
- 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
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
20132 Milano
Italie