Project description
The role of gut microbiota metabolites in brain inflammation
The gut microbiota is known for its physiological importance, and alterations in composition are associated with various diseases including multiple sclerosis (MS). The EU-funded BRAINeSs project is interested to understand how changes in short-chain fatty acids (SCFAs), key metabolites of microbiota, may lead to pathologies of the central nervous system. To achieve this, researchers will investigate the role of SCFAs in the blood–brain barrier, immune cells, neural stem cells, mature neurons and glial cells. Using a battery of state-of-the-art methodologies, BRAINeSs will assist in the development of novel interventions that may expand beyond MS to other neuroinflammatory or neurodegenerative diseases.
Objective
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.
Fields of science
- 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
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
20132 Milano
Italy