Dr. David J. Durgan and his colleagues at Baylor College of Medicine are committed to further understanding hypertension, especially the growing evidence that dysfunction of the gut microbiota, known as gut dysbiosis, may have a detrimental impact on blood pressure.
Intermittent Fasting And Lower Blood Pressure
“Previous research from our lab has shown that the makeup of the gut microbiota in hypertensive animal species, such as the SHRSP (spontaneously hypertensive stroke-prone rat) type, differs from that of animals with normal blood pressure,” said Durgan, an assistant professor of anesthesiology at Baylor.
The researchers have discovered that transplanting dysbiotic gut microbiota from a hypertensive animal into a normotensive (healthy blood pressure) animal causes the recipient to experience high blood pressure.
“This finding indicated that gut dysbiosis is not only an effect of hypertension but is also a cause of it,” Durgan said. “This preliminary research resulted in the present report, in which we proposed to address two questions. To begin, can we manipulate the dysbiotic microbiota to prevent or treat hypertension? Second, how do gut microbiota affect the animal’s blood pressure?”
Durgan and his collaborators used previous studies to address the first query, which showed that fasting was both a significant driver of the structure of the gut microbiota and a promoter of positive cardiovascular outcomes. However, no data linking the microbiota and blood pressure had been found in these trials.
The researchers created two classes using the SHRSP model of random hypertension and normal rats. The SHRSP and normal rats in one group were fed every other day, while the SHRSP and normal rats in the other group, called the test group, had an unlimited food supply.
The researchers discovered that, as predicted, the rats in the SHRSP control had higher blood pressure than the usual control rats nine weeks after the experiment started. Interestingly, as compared to the SHRSP rats that had not fasted, the SHRSP rats in the community who fasted every other day had slightly lower blood pressure.
“After that, we looked at how much the microbiota was involved in the blood pressure reduction we saw in the fasted SHRSP rats,” Durgan said.
The researchers transplanted the microbiota of rats that had either fasted or eaten without constraints into germ-free rats, who do not have their own microbiota.
Durgan and his collaborators were pleased to discover that germ-free rats given microbiota from normally fed SHRSP rats had higher blood pressure than germ-free rats given microbiota from regular control rats, just like their corresponding microbiota.
“It was especially interesting to see that germ-free rats that received microbiota from fasting SHRSP rats had substantially lower blood pressure than rats that received microbiota from SHRSP control rats,” Durgan said.
These findings showed that fasting-induced microbiota changes were necessary to mediate the blood pressure-lowering effect of intermittent fasting.”
The team then investigated the project’s second issue. What role does the gut microbiota play in blood pressure regulation?
Conducting a whole-genome shotgun microbiota sequence analysis as well as untargeted metabolomics analysis of plasma and gastrointestinal luminal material helped us with our understanding of the subject.
Changes in bile acid metabolism products stood out as possible mediators of blood pressure control among the changes we detected,” Durgan said.
SHRSP hypertensive animals, when fed, normally had lower bile acid levels in their blood than normotensive animals. But on the flip side, higher levels of bile acids were found in the blood of SHRSP animals on an intermittent feeding schedule.
“We observed that supplementing animals with cholic acid, the main bile acid, greatly lowered blood pressure in the SHRSP model of hypertension,” Durgan said.
Taken together, the findings reveal for the first time that intermittent fasting can help reduce hypertension in an animal model by reshaping the makeup of gut microbiota. The findings also show that gut dysbiosis leads to hypertension by modifying bile acid signaling.
“This research is significant because it demonstrates that fasting can have effects on the host by microbiota modulation,” Durgan said. “This concept has the potential to have wide applications of therapeutic uses.”