Modulation of brain barrier function by microbiota-derived factors in cerebral ischemia
The aim of our project "BiotaBrainBarrier" is to investigate the role of microbiota-derived factors in restoring compromised brain barrier function in cerebral ischemia. Recent evidence identifies the gut microbiota as a modulator of brain function in health and diseases also by acting on the different brain barriers ? the blood-brain barrier (BBB) and meninges. To date, it remains uninvestigated whether gut metabolites affect the dysfunction of brain barriers in stroke. Here we will combine the unique and complementary expertise of three laboratories: Experimental models of microbiota regulation in cerebral ischemia (Benakis, Germany), in vitro models of human gut and brain barriers (Mustafaoglu, Turkey), and therapeutic approaches in stroke patients (Hirt, Switzerland). The combined added value will allow us to address the following objectives: 1) Test microbial metabolites in modulating immune cell brain infiltration at the meningeal barrier; 2) Investigate underlying biological mechanisms of microbial metabolites on BBB and stroke outcome; 3) Correlate findings from an exploratory clinical trial using a microbial metabolite. Results derived from this original proposal have the great potential to provide new knowledge on brain barrier regulation in the context of stroke by critically probing the microbiota-derived component, bringing a novel target for developing innovative therapeutic strategies for individuals with cerebrovascular diseases.
