Scientists Explore Gut-Brain Impact on Stroke and Alzheimer’s Disease

Researchers at the Miami Project to Cure Paralysis are investigating strategies to help stroke and Alzheimer’s disease patients.

It’s not just a gut feeling.

Scientists recognize the strong interaction between the brain and the gut. Patients who suffer from traumatic brain injury or stroke often develop gastrointestinal problems.

The Brain-Gut Connection in Stroke and Alzheimer’s Disease

New research at the Miami Project to Cure Paralysis, a Center of Excellence at the University of Miami Miller School of Medicine, indicates a bidirectional relationship between the brain and the gut.

This means that people with conditions like colitis or irritable bowel syndrome may be more vulnerable to Alzheimer’s disease or cerebrovascular disorders like stroke. Likewise, people with neurological conditions like Alzheimer’s disease, or who have suffered a stroke, are also more likely to develop gut-related disorders.

Stroke remains the second leading cause of death worldwide and Alzheimer’s impacts more than 10 percent of Americans older than 65, making the work of the team at the Miami Project particularly relevant. Nadine Kerr, Ph.D., research assistant professor in the Miller School’s Department of Neurological Surgery, recently received a grant from the Alzheimer’s Association to study the bidirectional gut-brain axis after stroke and to take a look at patients 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 Dr. Kerr, who received a three-year, $250,000 grant. “Targeting underlying mechanisms could improve the quality of life for patients with chronic gut complications from developing Alzheimer’s disease or stroke.”

The Gut and Cognitive Decline

Dr. Kerr emphasizes the need to understand this process, as chronic gut problems, such as constipation, are often 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,” Dr. Kerr pointed out.

Dr. Kerr’s team is focused on how proteins called inflammasomes are transported from the brain to the gut through extracellular vesicles—small particles released into bodily fluids, such as blood, cerebrospinal fluid, and stool. This inflammatory response can happen within the first few days after a stroke.

In people diagnosed with Alzheimer’s disease, inflammasome activation in the brain and gut increases. Typically, once inflammasome pathways are activated, they trigger pyroptosis, a form of cell death that occurs in the brain and the gut. In 2022, the team published a paper revealing pyroptosis plays an important role in disrupting the gut-brain axis after stroke. With this grant, they hope to further understand how pyroptosis relates to Alzheimer’s disease and stroke.

Medications That Deter Inflammasome Transfer

Dr. Kerr hopes her team’s work identifies therapeutic drugs that block the transfer of inflammasomes to the gut and help stroke or Alzheimer’s patients 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, Dr. Kerr noted, by allowing clinicians to better understand how the brain communicates with the gut. Lifestyle changes like dietary modifications may help to reduce gut complications in patients with neurological disease.

“I’m sure most people have had some gut issues, diagnosed or not,” Dr. 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.”

Dr. Kerr’s team includes:

• Helen Bramlett, Ph.D., M.S., professor of neurological surgery
• W. Dalton Dietrich, Ph.D., scientific director of the Miami Project and professor of neurological surgery
• Juan Pablo de Rivero Vaccari, Ph.D., M.S.B.A., associate professor of neurological surgery
• Robert W. Keane, Ph.D., professor of physiology, biophysics, and neurological surgery

Tags: Alzheimer's disease, Department of Neurological Surgery, Miami Project to Cure Paralysis, stroke, USNWR Neuro