DESCRIPTION (provided by applicant): Recent studies have demonstrated that short chain fatty acid (SCFA) metabolites generated by gut microbes interact with G-protein coupled receptors in the host to affect host physiology. We recently found that two SCFA receptors in the vasculature - Gpr41, and Olfr78 - play roles in blood pressure regulation. These two receptors modulate blood pressure in response to changes in plasma levels of SCFAs. SCFAs are produced in the gut as a byproduct of gut microbial metabolism and are then absorbed into the bloodstream, and have previously been shown to play important roles in modulating a variety of physiological processes in the host, including metabolism and immune responses. Our recent data demonstrate a novel role for gut microbial metabolites in blood pressure control via SCFA receptors in the peripheral vasculature. Here, we seek to better understand this pathway by examining the mechanism underlying this response ex vivo and in vivo, and by determining whether we can purposefully manipulate gut microbial SCFA production in order to lower blood pressure in either normotensive or hypertensive mice. The proposed work invokes a variety of ex vivo and in vivo techniques in order to advance our understanding of blood pressure regulation. These studies have the potential to lead to potentially exciting future clinicl implications, as our data suggests that changes in gut microbial metabolism have the potential to modify baseline blood pressure.