It's not just a gut feeling.
For at least 15 years, scientists have recognized there is a strong interaction between the brain and the gut. Researchers and clinicians have shown that patients who suffer from acute brain injury, such as traumatic brain injury or stroke, often develop gastrointestinal problems.
And new research at the Miami Project to Cure Paralysis, a Center of Excellence at the University of Miami Miller School of Medicine, indicates that there is a bidirectional relationship between the brain and the gut.
This means that people with existing gut conditions—like colitis or irritable bowel syndrome—may be more vulnerable to develop a neurodegenerative condition like Alzheimer's disease or cerebrovascular disorders such as stroke. Likewise, people with existing neurological conditions like Alzheimer's disease, or who have suffered a stroke, are also more likely to develop gut related disorders.
Since stroke remains the second leading cause of death worldwide and Alzheimer's impacts more than 10 percent of Americans older than 65, a team at the Miami Project is actively working to understand the gut-brain connection. Toward that goal, Nadine Kerr, a research assistant professor in the Department of Neurological Surgery, recently received a grant from the Alzheimer's Association to study what is called the bidirectional gut-brain axis after stroke and to take a look at those diagnosed with Alzheimer's.
"Patients with Alzheimer's disease are more susceptible to stroke and also can suffer from gut disorders. We therefore proposed to examine how the bidirectional gut-brain axis plays a role in the development of Alzheimer's disease after stroke and long-term consequences," said Kerr, who received the three-year, $250,000 grant as a young investigator. "Targeting underlying mechanisms could improve the quality of life for patients with chronic gut complications from developing Alzheimer's disease or having a stroke."
Kerr emphasizes the need to critically study and understand this process because research has shown that chronic gut problems, such as constipation, are often more prone to accelerated cognitive decline.
"After stroke or getting Alzheimer's disease, people with gut problems often end up with worsened neurological outcomes, which is one of the main reasons why we chose to study the bidirectional communication between these organs," Kerr pointed out.
In particular, Kerr's team is focused on how proteins called inflammasomes are transported from the brain to the gut through extracellular vesicles. These are small particles released from various cell types into bodily fluids, such as blood, cerebrospinal fluid, and stool. This inflammatory response can happen within the first few days after a stroke.
Additionally, in people diagnosed with Alzheimer's disease there is a known increase in inflammasome activation in the brain and gut. Typically, once inflammasome pathways are activated, they trigger a process called pyroptosis, which is a form of cell death that occurs in the brain and the gut. In 2022, the team published a paper revealing that pyroptosis plays an important role in disrupting the gut-brain axis after stroke. With this grant, they hope to further understand this process and how it relates to Alzheimer's disease and stroke.
By understanding the mechanism of pyroptosis, Kerr said that she believes that her team may be able to study therapeutic drugs that could block the transfer of these inflammasomes to the gut. This potentially could help patients who have experienced stroke or Alzheimer's disease to avoid further systemic organ complications and progression of neurological deficits.
"Targeting extracellular vesicle signaling and pyroptotic cell death are mechanisms we are hoping to clarify that could lead to therapeutic interventions and biomarkers for the treatment and diagnosis of gut-brain axis complications after a central nervous system injury," she said. "And if we could do that, it could also likely improve a patient's long-term neurological conditions. So, there is less cognitive decline and gut complications."
But their work could also benefit other neurological disorders, Kerr noted, because it could allow clinicians to better understand how the brain communicates with the gut. Lifestyle changes, such as altering one's diet, improving the health of the gut microbiome, may help to reduce further gut complications in patients with neurological disease.
"I'm sure most people have had some gut issues, whether it is diagnosed or not," Kerr said. "The health of the gut is dependent on what we eat as well as other factors, studying how the brain and the gut interact and can be modified is really important."
Kerr's team science program includes Helen Bramlett, professor of neurological surgery; W. Dalton Dietrich, scientific director of the Miami Project and professor of neurological surgery; Juan Pablo de Rivero Vaccari, associate professor of neurological surgery; and Robert W. Keane, professor of physiology, biophysics, and neurological surgery.
