Gut bacteria may contribute to drug resistance

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New research in rodents suggests that gut bacteria can interfere with the efficacy of hypertensive medication. Paul Lense/Getty Images
  • Almost half of all adults in the United States have high blood pressure.
  • For around 20% of them, the condition does not respond to medication.
  • In a new study performed in rats, researchers have found that enzymes produced by some gut bacteria contribute to drug resistance, preventing antihypertensive medication from working.
  • Doctors may be able to predict which antihypertensive drugs are most likely to work by profiling people’s gut microbes.
  • By changing their diet or taking medications, people may be able to modify their gut microbes and increase the efficacy of some antihypertensive medications.

According to the Centers for Disease Control and Prevention (CDC), 47% of adults in the United States have hypertension, or high blood pressure. The International Society of Hypertension defines hypertension as blood pressure that is consistently higher than 140 over 90 millimeters of mercury (mm Hg).

People with hypertension are at higher risk of health complications, including heart disease, heart attack, and stroke.

For many people, hypertension can be controlled by medication, diet, and exercise. However, the CDC states that only 24% of people with hypertension have their condition under control.

Now, a study from the University of Toledo, Ohio, to be published in Experimental Biologyhas found that gut bacteria may explain why treatment is ineffective for some people.

Resistant hypertension is blood pressure that remains above 140/90 mm Hg despite treatment with three antihypertensive medications of different classes at the best-tolerated doses, one of which must be a diuretic.

Currently, doctors are resistant to hypertension by changing medication, or treat adding extra medications to those that are not working. However, some people give up their medication because of increased side effects from multiple treatments. Others remain hypertensive despite thorough medical management.

In this study, researchers looked at the gut microbiome of rats. They found that a common gut bacterium, Coprococcus comescan interfere with the action of some angiotensin-converting enzyme (ACE) inhibitors.

ACE inhibitorswhich include Lotensin (benazepril), Monopril (fosinopril), and Accupril (quinapril), are some of the most commonly used treatments for hypertension.

In the study, the researchers gave a single dose of quinapril to rats with high blood pressure. They found that the drug was less effective in reducing blood pressure in rats with a higher gut microbiota load.

To test their observations, they then gave the rats a combination of C. comes and quinapril. Rats given the combination had a smaller reduction in blood pressure than those given only quinapril.

They then performed in vitro tests and found that C. comes broke down quinapril; They suggest it does this by producing enzymes that hydrolyze the drug, making it less effective.

Prof. Tim Spector, professor of Epidemiology, King’s College London and lead of the Zoe Covid Symptom Study, told Medical News Today that the findings added to evidence about the effects of gut microbes:

“This contributes to the growing data that our gut microbes are crucial to how most common drugs work, and confirms similar studies with anti-depressant medication.”

And it is not just medications that may be affected by gut microbes. In a recent study, Prof. Spector and colleagues found that gut microbes can influence blood pressure in typical populations.

“We are still in the early stages of determining the interactions between gut bacteria and antihypertensive medications,” said Dr. Tao Yang, Ph. D., Assistant Professor at the University of Toledo, and presenting author of the study. “However, our current findings suggest that the same drug may not be appropriate for everyone because each person has a unique gut microbial composition with a unique profile of enzymatic activities.”

The authors are undertaking further experiments with different antihypertensives and other types of gut bacteria to further explore the interactions between gut microbiota and blood pressure medications.

Dr. Yang continued: “A better understanding of the relationship between gut microbes and drug efficacy could lead to new treatment approaches for people who don’t respond to blood pressure medication. This could include new drugs or modulating gut microbiota with probiotics, antibiotics, and other methods.”

“As we all have unique microbe gut communities, understanding how we can optimize them via personalized approaches to our diet is crucial for future health strategies.”

– Prof. Spector

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