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.

Public Health Relevance

We recently found that chemical sensors in your blood vessels help to modulate blood pressure by responding to chemicals made by the bacteria which live in your intestine. In this proposal, we will explore this pathway by studying how the chemical sensors regulate blood pressure, and by determining whether we can manipulate gut bacteria in order to affect predictable changes in blood pressure.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Hypertension and Microcirculation Study Section (HM)
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Maric-Bilkan, Christine
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Johns Hopkins University
Schools of Medicine
United States
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Pluznick, Jennifer L (2017) Microbial Short-Chain Fatty Acids and Blood Pressure Regulation. Curr Hypertens Rep 19:25
Rajkumar, P; Pluznick, J L (2017) Unsung renal receptors: orphan G-protein-coupled receptors play essential roles in renal development and homeostasis. Acta Physiol (Oxf) 220:189-200
Raizada, Mohan K; Joe, Bina; Bryan, Nathan S et al. (2017) Report of the National Heart, Lung, and Blood Institute Working Group on the Role of Microbiota in Blood Pressure Regulation: Current Status and Future Directions. Hypertension :
Natarajan, Niranjana; Hori, Daijiro; Flavahan, Sheila et al. (2016) Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genomics 48:826-834
Pluznick, Jennifer L (2016) Gut microbiota in renal physiology: focus on short-chain fatty acids and their receptors. Kidney Int 90:1191-1198
Natarajan, Niranjana; Pluznick, Jennifer L (2014) From microbe to man: the role of microbial short chain fatty acid metabolites in host cell biology. Am J Physiol Cell Physiol 307:C979-85