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Healing the gut may be the key to improving long-term recovery in stroke patients, scientists at Texas A&M University have found.

A paper published this fall in Brain, Behavior, and Immunity by researchers in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M College of Medicine is the latest of multiple studies highlighting the potential of this novel avenue of treatment, which takes advantage of the link between the brain and digestive system to curb cognitive impairment and other lingering impacts of a stroke or brain trauma.

The team demonstrated how a drug that was effective at protecting the brain in the immediate aftermath of a stroke failed to prevent long-term cognitive impairment when applied only to the brain. The same drug, when applied to the gut, reduced impairment significantly.

“Just fixing the brain directly won’t do it. As a neuroscientist, that was kind of shocking to me,” said Regents Professor and Department Head Dr. Farida Sohrabji. “But this tells us that if you don’t repair the gut, you won’t see (improvement in long-term function).”

The study builds on previous research led by Sohrabji, spearheaded by graduate student Yumna El-Hakim and associate research scientist Dr. Kathiresh Kumar Mani, exploring how the brain and gut influence each other during and after a stroke.

By understanding and leveraging the relationship between these systems, the team hopes to develop therapeutic techniques to prevent cognitive impairment in stroke patients and reduce their risk of developing dementia or Alzheimer’s disease (AD).

“Stroke is one of the leading causes of dementia and AD,” Sohrabji said. “While there are acute, immediate consequences of stroke, there are also these long-term consequences that affect quality of life for the patient as well as the caregivers, so there’s a lot of interest in understanding how to improve long-term outcomes.”

What happens in the gut after a stroke?

Within mere moments of a stroke, patients experience a cascade of symptoms, many of which are immediately apparent, Sohrabji said.

“You have individuals who can’t lift their arms, whose faces droop on one side, their speech is slurred,” she said. “That’s classic and occurs very, very quickly.”

Less apparent, she said, is the damage being done to key structures in the intestine, as the brain communicates to the gut that something is wrong. “What we’ve found is that minutes after a stroke occurs, normal gut anatomy is completely disrupted,” Sohrabji explained.

Most notably, cells responsible for keeping the contents of the gut sealed off from the rest of the body begin to erode, allowing digestive bacteria to leak out and cause harm to other bodily systems. Under certain conditions, Sohrabji said, these bacteria can end up in the brain itself and disrupt its functioning.

Even if bacteria don’t make it all the way to the brain, brain function can still be impaired as the body’s immune system recognizes the threat and mounts an inflammatory response to fight it. Increased inflammation exacerbates the impact of a stroke, further injuring the brain and increasing long-term cognitive impairment.

“If you just repair the brain, you will see short-term effects but not long-term improvement because the gut is still leaky,” Sohrabji said. “It’s (causing inflammation) and constantly impacting brain function in the long term.”

Heal the gut, save the brain

In the 2024 study, a treatment applied directly to the gut—a dose of Insulin-like Growth Factor or IGF-1—was shown to significantly reduce post-stroke inflammation and cognitive impairment. Sohrabji and her team’s investigation showed that the structures in the gut that become damaged after a stroke appeared to be repaired by the IGF-1 treatment, reinforcing the idea that healing the gut is crucial in facilitating stroke recovery.

In addition to its recent work with IGF-1, the team is exploring the use of stem cell transplants to rapidly repair the gut after a stroke—a treatment proposed by Mani that has proven effective in previous studies.

Under normal conditions, the gut produces a steady supply of stem cells to repair itself, Sohrabji said. Existing research shows that these cells can be transplanted from a healthy donor to a host with a damaged gut to speed up their recovery.

“We were fairly sure that (the stem cells) would repair the gut. What was not known, and what was a very pleasant surprise to us, was that in that process, it also improved stroke outcomes,” Sohrabji said. “As a result of (the treatment), the amount of dead tissue in the brain as a result of stroke was reduced and cognitive function was preserved.”

Sohrabji and her team plan to continue their work in this area, in hopes of developing a stem cell-derived treatment that could be administered to patients in the aftermath of a stroke to reduce the long-term risk for dementia and other adverse effects.