Understanding the multidirectional axes of communication between the gut microbiome and the brain in acute stress (360G-Wellcome-206704_Z_17_Z)

Different rodent strains exhibit different susceptibility to stress and release distinct levels of stress hormones into the gut during psychological stress1, this research will interrogate whether animal strain-dependent stress-response is reliant on gut microbiota-host interaction. We aim to identify a mechanism by which host genetic background interacts with the gut microbiota to generate a distinct animal stress-response phenotype. Host-derived neuroactive molecules are important signalling molecules in host-microbiota interaction along the microbiota-gut-brain axis2. Noradrenaline, a key catecholamine released into the intestinal lumen during stress-response, stimulates bacterial growth whereas microbe-derived products stimulate host enteric afferent nerves to influence host behaviour under stressful conditions3,4.Although the exaggerated stress-response of germ-free rodents (i.e. sterile animals without a microbiome) is normalized following microbial colonization6, it is unknown how host genetics influence host-microbe interaction to confer stress resilience. We will test the hypothesis that host genetic background is critical in determining whether the gut microbiota effect changes in host stress-response along the microbiota-gut-brain axis. We have established the following Key Objective to interrogate our hypothesis within an 8-week time-period: Define host-microbe interaction during psychological stress by characterizing microbial- and host-derived molecules and signalling along the microbiota-gut-brain axis in rodents.