Descripción del proyecto
El papel de los metabolitos de la microbiota intestinal en encefalitis
La microbiota intestinal es conocida por su importancia fisiológica y las alteraciones de su composición se relacionan con distintas enfermedades, incluida la esclerosis múltiple (EM). En el proyecto BRAINeSs, financiado con fondos europeos, están interesados en comprender cómo los cambios en los ácidos grasos de cadena corta (AGCC), metabolitos clave de la microbiota, pueden dar lugar a enfermedades del sistema nervioso central. Para ello, los científicos del proyecto investigarán el papel de los AGCC en la barrera hematoencefálica, las células inmunitarias, las células madre neuronales, las neuronas maduras y las células gliales. Mediante el uso de una batería de metodologías de última generación, BRAINeSs ayudará al desarrollo de nuevos tratamientos que puedan aplicarse más allá de la EM a enfermedades neuroinflamatorias o neurodegenerativas.
Objetivo
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.
Ámbito científico
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
- 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
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
20132 Milano
Italia