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Gut bacteria can make blood pressure medications less effective

A new study from the University of Toledo’s School of Medicine and Life Sciences shows that gut bacteria can reduce the effectiveness of some blood pressure medications.

Research published this month in the journal Hypertension It offers the first clues to what has been an elusive mystery – why some people don’t respond well to medication?

“Hypertension is often called the silent killer because it usually does not cause symptoms. However, a large number of individuals know they have high blood pressure but still cannot control it, even though they are taking blood pressure medications,” he said. Dr. Tao Yang, associate professor in the Department of Physiology and Pharmacology and first and lead author of the study. “Treatment of this matter is of significant clinical importance.”

High blood pressure is a major risk factor for heart disease and stroke, two of the leading causes of death in America. It is also one of the most common chronic conditions in the United States, with nearly half of adults in the United States considered to have high blood pressure according to current guidelines.

Among those with high blood pressure, 20% have what is known as resistant hypertension, which means that blood pressure remains high despite extensive treatment.

“The only thing doctors can really do for these patients is add or switch medications and increase the dose in hopes of finding something that works,” Yang said. “Until now, we have had no clear indication of the mechanism of resistant hypertension. Our research could provide a first step toward identifying new ways to effectively overcome treatment-resistant hypertension.”

In recent years, researchers have studied with greater interest the link between an individual’s blood pressure readings and the unique set of bacteria that live in their gut.

This work – much of which was done at UToledo – has helped reveal potential causes of high blood pressure that go beyond diet and exercise. However, Yang’s research is the first to study the effect of gut bacteria on blood pressure medications themselves.

Bena Gu, Distinguished University Professor and Chair of the Department of Physiology and Pharmacology at Utolido, and senior author of the study, said the research is an important extension of Utolido’s work to better understand the causes of high blood pressure and find new ways to treat it.

“Yang pioneered this important, highly translatable idea while training as a postdoctoral fellow in my lab,” she said. “This is now a major research topic in his own laboratory at the University of Toledo.”

In the study, UToledo scientists compared the antihypertensive drug quinapril’s effectiveness in rats with normal gut bacteria against those whose gut bacteria had been depleted with high doses of antibiotics.

The researchers found a clear difference between the two, with animals given the antibiotics responding much better to quinapril.

Analysis of the gut bacteria composition of animals identified Coprococcus as the culprit. Laboratory experiments have proven that cuprocox, a dominant bacteria in this genus, can break down quinapril and ramipril, resulting in a blood pressure lowering effect.

While the UToledo study was limited to animal models and lab experiments, the researchers identified at least one interesting case study that appears to strengthen the argument that this finding can be applicable to humans.

A 2015 report, published 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 for two weeks in which she was taking antibiotics for a postoperative infection. Her blood pressure could have been controlled with just one drug for six months after stopping the antibiotics before becoming resistant to treatment again.

“This is just one report and more research is needed. However, this does suggest that gut bacteria can play a very real and important role in regulating the effectiveness of blood pressure medications,” Yang said.

The research group plans to continue its work by studying the interaction between additional blood pressure medications and other common types of gut bacteria.

Although long-term antibiotic use isn’t a realistic strategy for treating treatment-resistant hypertension, Yang said it should be possible for someone to alter their microbiota through probiotics, prebiotics, and changes in diet.

“The ultimate goal of my research is to identify ways in which we can specifically target bacteria in an individual’s gut to improve drug efficacy,” he said. “This has the potential to benefit a lot of people.”

Dr. Young Oh, program officer at the National Heart, Lung, and Blood Institute, agrees that this study represents an important piece of the puzzle in understanding resistant hypertension. The study was supported in part by the NHLBI, which is part of the National Institutes of Health.

“Studies have been done on the gut microbiome as it relates to high blood pressure,” said Oh, who was not a member of the study team. “While this study fills an important knowledge gap, more studies, especially in humans, are needed to confirm the findings.”

The research was supported in part by a grant from the American Heart Association.

The research reported in this release was supported in part by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, under the following grant numbers: R01HL143082 and HL132448.

2022-05-26 16:08:20

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