Emerging risk factors for stroke: Deciphering the biological mechanisms underlying the impact of chronic stress on the microbiome and microglia epigenetics.

Objective

According to the World Stroke Organization (WSO), stroke is the third-leading cause of death and disability worldwide, with an estimated total cost of €60 billion in Europe. The number of people living with stroke is estimated to increase of 27% within 2047. In the last years, an increased incidence of stroke was observed among younger population, due to exposure to emerging risk factors such as stress. The leading role of the gut microbiota in stroke outcome has been demonstrated by the pioneering works conducted by Dr. Benakis, supervisor at the host Institute for Stroke and Dementia (ISD), showing that microbiota can influence brain damage severity. During my Ph.D., I demonstrated that stress exposure leads to alteration in microbiota composition, resulting in the production and accumulation in the brain of the microbial-derived uremic toxin p-cresol, which has been associated with an increased incidence of ischemic stroke. However, there are currently no studies exploring the correlation between stress, microbiota, and stroke, leaving a great gap that could have substantial clinical implications. The MicroStress project aims to investigate, for the first time, the relationship between chronic stress and stroke through microbiota alteration, combining in vivo and molecular cutting-edge technologies including metabolomic and epigenetic assays. Moreover, this project proposes a therapeutic approach using synbiotic – a mixture of probiotic and prebiotic – to modify microbiota composition and ameliorate stroke outcome. The combination of Dr. Benakis’ expertise in the microbiota-immune system-stroke interaction and my experience in stress-microbiota research will be fundamental to closing this gap. The MicroStress project is a unique opportunity to acquire new scientific and transferable skills, essential for achieving the project’s objectives and advancing towards an independent research career.