Fasting lowers blood pressure by reshaping the gut microbiota
rael-science
Fasting lowers blood pressure by reshaping the gut microbiota
Nearly
half of adults in the United States have hypertension, a condition that
raises the risk for heart disease and stroke, which are leading causes
of death in the U. S.
At
Baylor College of Medicine, Dr. David J. Durgan and his colleagues are
dedicated to better understand hypertension, in particular the emerging
evidence suggesting that disruption of the gut microbiota, known as gut
dysbiosis, can have adverse effects on blood pressure.
"Previous
studies from our lab have shown that the composition of the gut
microbiota in animal models of hypertension, such as the SHRSP
(spontaneously hypertensive stroke-prone rat) model, is different from
that in animals with normal blood pressure," said Durgan, assistant professor of anesthesiology at Baylor.
The
researchers also have shown that transplanting dysbiotic gut microbiota
from a hypertensive animal into a normotensive (having a healthy blood
pressure) one results in the recipient developing high blood pressure.
"This
result told us that gut dysbiosis is not just a consequence of
hypertension, but is actually involved in causing it," Durgan said.
"This ground work led to the current study in which we proposed to
answer two questions. First, can we manipulate the dysbiotic microbiota
to either prevent or relieve hypertension? Second, how are the gut
microbes influencing the animal's blood pressure?"
Can manipulating the gut microbiota regulate blood pressure?
To
answer the first question, Durgan and his colleagues drew on previous
research showing that fasting was both one of the major drivers of the
composition of the gut microbiota and a promoter of beneficial
cardiovascular effects. These studies, however, had not provided
evidence connecting the 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 unrestricted food availability.
Nine
weeks after the experiment began, the researchers observed that, as
expected, the rats in the SHRSP control had higher blood pressure when
compared to the normal control rats. Interestingly, in the group that
fasted every other day, the SHRSP rats had significantly reduced blood
pressure when compared with the SHRSP rats that had not fasted.
"Next,
we investigated whether the microbiota was involved in the reduction of
blood pressure we observed in the SHRSP rats that had fasted," Durgan
said.
The
researchers transplanted the microbiota of the rats that had either
fasted or fed without restrictions into germ-free rats, which have no
microbiota of their own.
Durgan
and his colleagues were excited to see that the germ-free rats that
received the microbiota of normally fed SHRSP rats had higher blood
pressure than the germ-free rats receiving microbiota from normal
control rats, just like their corresponding microbiota donors.
"It
was particularly interesting to see that the germ-free rats that
received microbiota from the fasting SHRSP rats had significantly lower
the blood pressure than the rats that had received microbiota from SHRSP
control rats," Durgan said. "These results demonstrated that the
alterations to the microbiota induced by fasting were sufficient to
mediate the blood pressure-lowering effect of intermitting fasting."
How the microbiota regulates blood pressure
The team proceeded to investigate the second question of their project. How does the gut microbiota regulate blood pressure?
"We
applied whole genome shotgun sequence analysis of the microbiota as
well as untargeted metabolomics analysis of plasma and gastrointestinal
luminal content. Among the changes we observed, alterations in products
of bile acid metabolism stood out as potential mediators of blood pressure regulation," Durgan said.
The
team discovered that the SHRSP hypertensive animals that were fed
normally had lower bile acids in circulation than 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," Durgan said.
Taken
together, the study shows for the first time that intermittent fasting
can be beneficial in terms of reducing hypertension by reshaping the
composition of 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 to understand that fasting can have its effects on
the host through microbiota manipulation," Durgan said. "This is an
attractive idea because it can potentially have clinical applications.
Many of the bacteria in the gut microbiota are
involved in the production of compounds that have been shown to have
beneficial effects as they make it into the circulation and contribute
to the regulation of the host's physiology. Fasting schedules could one
day help regulate the activity of gut microbial populations to naturally
provide health benefits."
