In the fight against high blood pressure and depression, there’s a new target being investigated by University of Florida Health researchers: gut bacteria. People with both conditions appear to have a distinct microbial profile in their digestive tract, the researchers have found.
The discovery is significant because it could eventually revolutionize the way scientists and physicians approach the diagnosis and treatment of hypertension and depression, the study’s lead investigator said.
“We believe we have discovered new forms of high blood pressure. The gut could now be a novel target for preventing, diagnosing and treating hypertension and depression,” said Bruce R. Stevens, Ph.D., a professor of physiology and functional genomics in the UF College of Medicine. The findings were presented recently at the American Heart Association’s Hypertension Scientific Session.
High blood pressure and depression are interrelated in many people yet unlinked in others. Cardiologists and psychiatrists don’t know why and that makes diagnosis and treatment challenging, Stevens said. He and his colleagues approached the problem from a different perspective: That the human body is a “meta-organism,” a complex, intercommunicating system of trillions of bacterial cells that coexist with a roughly equal number of human cells in the body. This fits the picture that hypertension may be a mosaic of diseases rather than a single entity, according to Stevens.
To establish their findings, the researchers collected stool samples from adults who had hypertension, depression or both, as well as specimens from healthy people. A sophisticated DNA analysis revealed that each group of participants had a unique gut bacteria profile. People with and without hypertension were clearly distinguishable from each other based on the genes and biochemical processes of their gut bacteria, the researchers found.
“Based on their gut bacteria, we can identify whether or not people belong to a group of patients who have hypertension and depression,” Stevens said.
Ultimately, Stevens and his colleagues identified what they say are three new, separate disorders: they are naming one type “depressive-hypertension” in people who have both depression and high blood pressure. The other types are non-depressive hypertension and non-hypertensive depression. Those with depressive hypertension had gut bacteria with a distinct metabolic profile that is known to affect blood pressure.
Understanding how gut bacteria interact with the rest of the body is an important first step toward designing therapies based on the genetic profile of a patient’s gut bacteria, according to Stevens.
Carl J. Pepine, M.D., a collaborator on the research and a professor in the UF College of Medicine’s department of medicine, said the findings are early but have considerable potential. They could perhaps lead to a novel treatment by implanting selected or modified gut bacteria from a healthy person into a patient with depressive hypertension, he said.
“We can use the bacteria or their metabolites to create a ‘signature’ to better diagnose, classify and manage such patients, which at present can be challenging,” he said. Pepine also has an ongoing clinical trial to evaluate the antibiotic minocycline’s effectiveness against treatment-resistant hypertension.
Because some antidepressants and blood pressure medications also have anti-microbial properties, Stevens and the UF team of researchers are also studying whether those medications can be repurposed to influence the bacteria that drive hypertension and depression.
Mohan K. Raizada, Ph.D., a collaborator on the research and a distinguished professor of physiology and functional genomics in the UF College of Medicine, was the first to discover a link between gut bacteria and hypertension in 2010. Raizada said he is encouraged by the findings because nearly half of American adults have high blood pressure and about 20% of them do not respond to medication.
“If this concept holds up with additional testing, then we can design a therapy to treat depressive hypertension,” Raizada said.
Next, researchers want to better understand the mechanism of the bidirectional communications between gut bacteria and brain. That means finding out more about whether gut bacteria and their inflammatory effects influence the brain’s connections involving mood centers and blood regulation centers or if the brain has a “top-down” impact on the gut, Stevens said. The UF Health researchers are planning on transplanting bacteria from depressed and hypertensive people into mouse models to find out whether they take on those disease properties.
“This is where the future is going — treating depression and high blood pressure from a gastrointestinal perspective with an eye on manipulating gut bacteria using antibiotics, probiotics, fecal transplantation or dietary manipulation,” Stevens said.
The National Heart, Lung and Blood Institute and UF’s Clinical and Translational Science Institute and the department of physiology and functional genomics funded the study.