Healing the gut may reduce the long-term effects of a stroke, according to research from Texas A&M

Scientists at Texas A&M University have found that healing the gut could be the key to improving long-term recovery for stroke patients.

A paper published this fall by researchers in the Department of Neuroscience and Experimental Therapeutics at Texas A&M College of Medicine is the latest in several studies highlighting the potential of this novel treatment that harnesses the connection between the brain and digestive system to treat cognitive impairment and to curb other lasting effects of a stroke or brain trauma.

The team showed that a drug that effectively protected the brain immediately after a stroke failed to prevent long-term cognitive impairment when applied only to the brain. The same drug significantly reduced impairment when applied to the intestines.

“Just repairing the brain directly is not enough. As a neuroscientist, that was kind of shocking to me,” said Regents Professor and Department Head Dr. Farida Sohrabji. “But this shows us that if you don’t repair the gut, you’re not going to see (improvement in long-term function).”

The study, which appears in the November issue of Brain, behavior and immunitybuilds on Sohrabji’s previous research led by graduate student Yumna El-Hakim and associate research scientist Dr. Kathiresh Kumar Mani and examines how the brain and gut influence each other during and after a stroke. By understanding and exploiting 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). Their work is supported by a National Institutes of Health grant to Sohrabji and additional funding from the WoodNext Foundation.

“Stroke is a leading cause of dementia and AD,” Sohrabji said. “While a stroke has acute, immediate consequences, there are also long-term consequences that impact the quality of life of the patient and caregiver. Therefore, there is great interest in understanding how to improve long-term outcomes.”

What happens in the intestines after a stroke?

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

“There are people who cannot lift their arms, whose faces are slouched to the side and whose speech is slurred,” she said. “It’s classic and happens very, very quickly.”

Less obvious, she said, is the damage that occurs to key structures in the gut, as the brain tells the gut that something is wrong. “We found that normal intestinal anatomy is completely disrupted minutes after a stroke,” Sohrabji explained.

In particular, cells responsible for sealing off the intestinal contents from the rest of the body begin to erode, allowing digestive bacteria to leak out and damage other body systems. Under certain conditions, says Sohrabji, these bacteria could end up in the brain itself and disrupt its function. Even if bacteria do not reach the brain, brain function can still be impaired because the body’s immune system recognizes the threat and mounts an inflammatory response to combat it. Increasing inflammation worsens the effects of a stroke, further damaging the brain and increasing long-term cognitive impairment.

“If you just repair the brain, you will see short-term effects but no long-term improvement because the gut is still leaky,” Sohrabji said. “It causes inflammation and affects long-term brain function.”

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 inflammation and cognitive impairment after a stroke. Sohrabji and her team’s research found that the structures in the intestine that were damaged after a stroke appeared to be repaired by IGF-1 treatment.

In addition to its recent work with IGF-1, the team is studying the use of stem cell transplants to quickly repair the intestine after a stroke – a treatment proposed by Mani that has been shown to be effective in previous studies.

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

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

Sohrabji and her team plan to continue their work in this area in hopes of developing a stem cell-based treatment that could be given to patients after a stroke to reduce the long-term risk of dementia and other side effects.