Almost half of adults in the United States have hypertension, a condition that increases the risk of heart disease and stroke, which are the leading causes of death in the United States.
At Baylor College of Medicine, Dr David J. Durgan and colleagues are dedicated to better understanding hypertension, especially new evidence suggesting that the disruption of the gut microbiota, known as gut dysbiosis, can have adverse effects. on blood pressure.
“Previous studies in our laboratory have shown that the composition of the gut microbiota in animal models of hypertension, such as the SHRSP (spontaneously hypertensive rat prone to stroke) model, is different from that of animals with normal blood pressure,” said Durgan, assistant professor of anesthesiology at Baylor.
Researchers have also shown that transplanting dysbiotic gut microbiota from a hypertensive animal to a normotensive (having healthy blood pressure) results in high blood pressure in the recipient.
“This result told us that gut dysbiosis is not only a consequence of hypertension, but is actually implicated in its cause,” said Durgan. “This fieldwork led to the current study in which we proposed to answer two questions. First, can we manipulate the dysbiotic microbiota to prevent or relieve hypertension? Second, how do gut microbes influence the blood pressure of the animal? “
Can manipulation of the gut microbiota regulate blood pressure?
To answer the first question, Durgan and his colleagues drew on previous research showing that fasting was both a major driver of gut microbiota makeup and a promoter of beneficial cardiovascular effects. These studies, however, did not provide any evidence linking microbiota and blood pressure.
Working with the SHRSP model of spontaneous hypertension and normal rats, the researchers set up two groups. One group had SHRSP and normal rats that were fed every other day, while the other group, called control, had SHRSP and normal rats with unlimited food availability.
Nine weeks after the start of the experiment, the researchers observed that, as expected, the rats in the SHRSP control had higher blood pressure than the normal control rats. Interestingly, in the group that fasted every other day, the SHRSP rats had significantly reduced blood pressure compared to the SHRSP rats that did not fast.
“Next, we looked at whether the microbiota was involved in the reduction in blood pressure that we observed in the SHRSP rats that had fasted,” said Durgan.
The researchers transplanted the microbiota from rats that had fasted or fed unrestrictedly to germ-free rats, which lack their own microbiota.
Durgan and his colleagues were delighted to see that the germ-free rats that received the microbiota from normally fed SHRSP rats had higher blood pressure than the germ-free rats that received the microbiota from normal control rats, as did their corresponding microbiota donors.
“It was particularly interesting to see that the germless rats that received the microbiota from the fasting SHRSP rats had significantly lower blood pressure than the rats that received the microbiota from the SHRSP control rats,” said Durgan. “These results demonstrated that the microbiota alterations induced by fasting were sufficient to mediate the hypotensive effect of intermittent fasting.”
How the microbiota regulates blood pressure
The team proceeded to study the second question of their project. How does the gut microbiota regulate blood pressure?
“We applied the shotgun sequence analysis of the entire microbiota genome as well as the non-targeted metabolomic analysis of plasma and gastrointestinal luminal content. Among the changes we observed, alterations in the products of the Bile acid metabolism have emerged as potential mediators of blood pressure regulation, ”said Durgan.
The team found that the hypertensive SHRSP animals that were fed normally had lower circulating bile acids than the normotensive animals. On the other hand, SHRSP animals that followed an intermittent feeding schedule had more bile acids in the circulation.
“Supporting this finding, we found that supplementing animals with cholic acid, a primary bile acid, also significantly reduced blood pressure in the SHRSP model of hypertension,” said Durgan.
Overall, the study shows for the first time that intermittent fasting can be beneficial in terms of reducing hypertension by reshaping the composition of the gut microbiota in an animal model. The work also provides evidence that gut dysbiosis contributes to hypertension by altering bile acid signaling.
“This study is important for understanding that fasting can have its effects on the host through manipulation of the microbiota,” said Durgan. “It’s an interesting idea because it has the potential to have clinical applications. Many bacteria in the gut microbiota are involved in the production of compounds that have been shown to have beneficial effects when released and help regulate host physiology. Fasting schedules may one day help regulate the activity of gut microbial populations to provide natural health benefits. “