Feature | March 04, 2013

Blood Vessels 'Sniff' Gut Microbes to Regulate Blood Pressure

March 4, 2013 — Researchers at The Johns Hopkins University and Yale University have discovered that a specialized receptor, normally found in the nose, is also in blood vessels throughout the body, sensing small molecules created by microbes that line mammalian intestines, and responding to these molecules by increasing blood pressure. The finding suggests that gut bacteria are an integral part of the body’s complex system for maintaining a stable blood pressure.

A description of the research, conducted in mice and test tubes, appeared online Feb. 11 in the journal Proceedings of the National Academy of Sciences.

“The contribution that gut microbes apparently make to blood pressure regulation and human health is a surprise,” says Jennifer Pluznick, Ph.D., assistant professor of physiology at the Johns Hopkins University School of Medicine. “There is still much to learn about this mechanism, but we now know some of the players and how they interact,” she adds.

Pluznick says that several years ago, thanks to a “happy coincidence,” she found — in the kidney — some of the same odor-sensing proteins that give the nose its powers. Focusing on one of those proteins, olfactory receptor 78 (Olfr78), her team specifically located it in the major branches of the kidney’s artery and in the smaller arterioles that lead into the kidney’s filtering structures. Olfr78 also turned up in the walls of small blood vessels throughout the body, she says, particularly in the heart, diaphragm, skeletal muscle and skin.

To figure out which molecules bind and activate Olfr78, the scientists programmed cells to have Olfr78 protein receptors on their surface. They also gave these same cells the ability to start a light-producing chemical reaction whenever Olfr78 is activated. By adding different cocktails of molecules to the cells and measuring the light the cells produced, they homed in on a single mixture that activated Olfr78. They then tested each component in that mix and found that only acetic acid (a.k.a. vinegar) bound Olfr78 and caused the reaction.

Acetic acid and its alter ego, acetate, are part of a group of molecules known as short chain fatty acids (SCFAs). When the team tested other molecules in this group, they found that propionate, which is similar to acetate, also binds Olfr78. In the body of mammals, including humans, SCFAs are made when zillions of bacteria lining the gut digest starch and cellulose from plant-based foods. The SCFAs are absorbed by the intestines into the blood stream, where they can interact with Olfr78.

To pinpoint the effect of Olfr78, the scientists gave SCFAs to mice missing the Olfr78 gene and found that the rodents’ blood pressure decreased, suggesting that SCFAs normally induce Olfr78 to elevate blood pressure. However, when they gave SCFAs to normal mice with intact Olfr78, they did not see the expected increase in blood pressure, but rather a decrease, though it was less pronounced than before.

To test the effect of reducing the SCFAs available to Olfr78, the team gave mice a three-week course of antibiotics to wipe out the gut microbes responsible for SCFA production. In this case, normal mice showed very little change in blood pressure, but mice without Olfr78 experienced an increase in blood pressure, suggesting that there were other factors involved in the Olfr78/SCFA/blood pressure relationship.

The mystery was solved, Pluznick says, when the team examined mice lacking Gpr41, a non-smell-related protein receptor located in blood vessel walls that also binds SCFAs. When SCFAs bind to Gpr41, blood pressure is decreased. The researchers eventually discovered that Olfr78 and Gpr41 both are activated by SCFAs, but with contradictory effects. The negative effect of Gpr41 is counterbalanced by the positive effect of Olfr78, but Gpr41’s effect is stronger, so an increase in SCFAs produces an overall decrease in blood pressure.

“We don’t have the full story yet,” says Pluznick. “There are many players involved in the maintenance of stable levels of blood pressure, and these are just a few of them. We don’t know why it would be beneficial for blood pressure to decrease after eating or why gut microbes would play a part in signaling that change. But our work opens the door for exploring the effects of antibiotic treatments, probiotics and other dietary changes on blood pressure levels in mice, and perhaps eventually people.”

Other authors of the report include Ryan Protzko of the Johns Hopkins University School of Medicine; Jinah Han, La-Xiang Wan, Tong Wang, Anne Eichmann and Michael Caplan of the Yale University School of Medicine; Haykanush Gevorgyan, Arnold Sipos and Janos Peti-Peterdi of the University of Southern California; and others from the College de France, Columbia University, the Washington University School of Medicine and the University of Texas Southwestern Medical Center.

This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK081610, DK64324, DK17433) and the Leducq Foundation.

Related Content

cardiac surgery, simulation training, University of Washington, case studies

Multiple repetitions of bypass grafts on a heart, using the Ramphal simulator. Courtesy of the University of Washington in Seattle.

News | Cardiovascular Surgery| August 25, 2016
August 25, 2016 — Simulation training fo
aortic dissection, family history, same age, clinical study, John A. Elefteriades, Annals of Thoracic Surgery
News | Structural Heart| August 25, 2016
People with a family member who had an aortic dissection — a spontaneous tear in one of the body’s main arteries —...
Intact Vascular, TOBA clinical study, one-year results, Tack Endovascular System, Journal of Vascular Surgery
News | Peripheral Arterial Disease (PAD)| August 24, 2016
Intact Vascular Inc. announced that the one-year results from its Tack Optimized Balloon Angioplasty (TOBA) clinical...
nanoparticles, blood clotting, internal bleeding, American Chemical Society study, Erin B. Lavik

Nanoparticles (green) help form clots in an injured liver. The researchers added color to the scanning electron microscopy image after it was taken. Image courtesy of Erin Lavik, Ph.D.

News | Hemostasis Management| August 24, 2016
August 24, 2016 — Whether severe trauma occurs on the battlefield or the highway, saving lives often comes down to...
Mayo Clinic, blood test, heart attack risk, plasma ceramides
News | Cardiac Diagnostics| August 24, 2016
August 24, 2016 — Mayo Clinic has launched a new type of ...
Apollo astronauts, cardiovascular death, FSU study, Florida State University, cosmic radiation

International Space Station image courtesy of NASA

News | Cardiac Diagnostics| August 24, 2016
August 24, 2016 — Members of the successful Apollo space program are experiencing...
Technavio report, renal denervation devices, 2015
News | Renal Denervation| August 23, 2016
August 23, 2016 — Technavio analysts forecast the global...
News | Heart Failure| August 23, 2016
August 23, 2016 — A new study of more than 13,000 people has found that so-called morbid obesity appears to stand alo
Jason Burdick, injectable hydrogels, heart failure, heart attack, American Chemical Society

Compared to other types of hydrogels being developed (left), a new hydrogel (right) can form crosslinks after injection into the heart, making the material stiffer and longer-lasting. Image courtesy of American Chemical Society.

News | Heart Failure| August 23, 2016
August 23, 2016 — During a heart attack, clots or narrowed arteries block blood flow, harming or killing cells within
sleep apnea, hypertension, clinical study, Science Signaling, University of Chicago
News | Hypertension| August 22, 2016
Obstructive sleep apnea is a common cause of high blood pressure. In the Aug. 17, 2016, issue of the journal Science...
Overlay Init