More and more people are living with high blood pressure that is resistant to therapeutic treatments. Now, U.S. scientists have concluded in a novel experimental study that one of the causes is gut bacteria, which can make blood pressure medications less effective.

The findings of a study at the University of Toledo in Ohio on the microbiome open the door to identifying new ways of overcoming treatment-resistant hypertension. The key lies in the intestinal bacteria, which determine the efficacy of antihypertensive drugs.

This experimental work, published in Hypertension, demonstrates that gut bacteria can reduce the efficacy of certain blood pressure drugs.

It is well known among nephrology clinicians that many people are unable to reduce their blood pressure with one or two antihypertensive drugs, plus a diuretic, so they have to make combinations to achieve the goal.

Now, this team, led by Professor Tao Yang, Department of Physiology and Pharmacology at the University of Toledo, has found that the cause lies in the gut bacteria that make up the microbiome.

“High blood pressure is often called a silent killer because it usually causes no symptoms. However, there are a large number of people who know they have hypertension but still cannot control it, even though they are taking medication for it,” emphasizes Professor Yang.

Hypertension, or high blood pressure, is a major risk factor for heart disease and stroke, two of the leading causes of death in the United States. It is also one of the most common chronic conditions, with nearly half of U.S. adults considered hypertensive according to current protocols.

It is estimated that among people with high blood pressure, 20% have what is known as resistant hypertension, meaning that their blood pressure remains high despite therapeutic treatment.

Resistant hypertension

“The only thing doctors can really do in these patients is to add or change medications and increase the dose in the hope that they can find something that works,” explains Professor Yang.

“So far,” he acknowledges, “we haven’t had any clear indication of what the mechanism is for resistant hypertension. Our microbiome research could provide a first step toward identifying new ways to overcome it effectively.”

In recent years, researchers have taken a closer look at the relationship between an individual’s blood pressure numbers and the unique collection of bacteria living in his or her gut.

This study has helped unravel possible causes of hypertension that extend beyond diet and exercise. Professor Yang’s research is the first to examine the impact of the gut microbiome and bacteria on blood pressure medications.

In this regard, Professor Bina Joe, chair of the Department of Physiology and Pharmacology at the same campus and lead author of the study, says the research is a significant extension of work to better understand the causes of hypertension and find new ways to treat it. “Yang,” she stresses, “pioneered this important and highly translational idea during his training as a postdoctoral fellow in my lab. It is now a major research topic in his own lab at the University of Toledo.”

In the study, the scientists compared the efficacy of an antihypertensive drug in rats with normal gut bacteria versus those whose gut microbiota had been depleted by high doses of antibiotics.

The researchers found a clear difference between the two, with the animals that received antibiotics first responding much better to the antihypertensive.

Microbiome, the key

Analysis of the composition of gut bacteria in the animals identified the bacterium Coprococcus as the culprit. Laboratory experiments showed that Coprococcus comes, a dominant bacterial species in this genus, can break down that drug and others, resulting in compromised blood pressure-lowering effects.

While this work was limited to animal models and laboratory experiments, the researchers identified at least one study that appears to bolster the argument that this finding could be applicable to people.

That 2015 paper, reported in the International Journal of Cardiology, described a woman with a long history of treatment-resistant hypertension whose blood pressure was controlled without any antihypertensive medication during the two weeks she was taking antibiotics for a postsurgical infection.

His blood pressure was able to be controlled with a single medication for six months after stopping antibiotics before becoming resistant to treatment. “This is only one study and more research is needed. However, it suggests that gut bacteria may play a very real and very important role in regulating the efficacy of blood pressure medications,” Professor Yang points out.

This team of scientists now intends to study the interaction between additional blood pressure medications and other common types of gut bacteria.

Although long-term use of antibiotics is not a realistic strategy to address treatment-resistant hypertension, Professor Yang believes that it should be possible for someone to alter their microbiota through probiotics, prebiotics and dietary changes.

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