The BRAINeSs project arose from the scientific and clinical necessity to clarify the role of the microbiota-gut-brain axis in neuroinflammatory diseases, considering both the molecular and cellular points of view.
Recent studies pointed out that gut microbiota dysbiosis is a triggering event in a plethora of intestinal and extra-intestinal diseases, among them the outcome of autoimmune diseases such as multiple sclerosis (MS).
The microbiota communicates with the host mainly through the synthesis and secretion of specific metabolites that cannot be produced by host cells but are fundamental for their function. Among these metabolites, there are the short-chain fatty acids (SCFAs), molecules that regulate multiple functions, among them stemness, tissue integrity, gene expression, and induction of pro-tolerogenic immune response.
SCFAs supplementation has been proven beneficial in both the experimental autoimmune encephalomyelitis (EAE) model of MS and MS patients. In both cases, the authors analyze mainly their pro-tolerogenic role on the immune system, overlooking their impact on the nervous tissue, the primary disease target.
With the BRAINeSs project, I proposed a ground-breaking research that will establish novel regulatory mechanisms by which SCFAs modulate the pathogenesis of MS directly at the central nervous system (CNS), by deciphering three main research questions or specific objectives: 1. SCFAs and NPCs: How do SCFAs influence NPC's self-renewal and differentiation? 2. SCFAs and immunity. 3. SCFAs and neuronal/glial cells: How do SCFAs influence the physiology of mature neuronal & glial cells and their mutual communication?
Answering these questions is important for society since my finalized results could be easily translated into clinical practice, especially for patients with neuroinflammatory/neurodegenerative disorders (MS, Alzheimer’s, Parkinson’s, etc.), but also to prevent these disorders in high-risk subjects (e.g. dysbiotic subjects or individuals with genetic predisposition), with an impact on EU public health and economy.
Conclusions: The BRAINeSs project shed light on the importance of SCFAs for the physiology of the CNS. In particular, I found that SCFAs have a strong protective effect in the case of oxidative stress and are modulated not only in the gut but on a whole body scale in the frame of MS, both in the mouse model and in patients. With the BRAINeSs project, I show that SCFAs modulate not only the systemic and brain immune system but also the nervous system.
