Short-Chain fatty acids in brain neuroinflammation: modulators of immunity and neural stemness
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.