Correcting imbalance with the gut microbiota after stroke could reduce brain inflammation, open pathway to potential therapies

An imbalance in ligands, which are molecules produced by the body and the gut microbiota, can affect a key receptor protein that plays a role in brain inflammation after stroke, according to researchers at UTHealth Houston, who recently published their preclinical findings in Nature Communications.

The researchers studied host-derived ligands, those produced by the host body, and microbiota-derived ligands, which are produced only by gut microbiota fermentation.

Both of the ligand types affect the aryl hydrocarbon receptor (AHR), which is involved in immune regulations and inflammation. After a stroke, a metabolite called kynurenine, a host-derived ligand for AHR, increases. Meanwhile, stroke-induced dysbiosis – disruption of the gut microbiota – can lead to a loss of microbiota-derived ligands, which in turn would have a negative effect on the balance of AHR signaling.

“This study looked at how substances from the body and gut bacteria called AHR ligands affect post-stroke inflammation,” said senior author Bhanu Priya Ganesh, PhD, associate professor of neurology with McGovern Medical School at UTHealth Houston. “They found that after a stroke, changes in gut bacteria lead to a drop in beneficial substances and an increase in harmful ones. This suggests that restoring these beneficial substances from gut bacteria could help reduce inflammation after a stroke.”

Previous UTHealth Houston preclinical, animal-model research showed that stroke and neurodegenerative diseases create systemic responses in which the gut microbiota plays a key role, and aging worsened stroke-induced dysbiosis.  

“Our recent animal-model study points to new treatment options that could focus on the gut-brain connection, offering potential ways to improve recovery after a stroke and reduce brain damage,” Ganesh said.

First author was neurosurgery resident Pedram Peesh, MD, PhD, MBA, with the Vivian L. Smith Department of Neurosurgery at McGovern Medical School. Louise McCullough, MD, PhD, professor and Roy M. and Phyllis Gough Huffington Distinguished Chair in the Department of Neurology at McGovern Medical School, is co-corresponding author with Ganesh. Ganesh, McCullough, and Peesh are members of The University of Texas MD Anderson Center UTHealth Houston Graduate School of Biomedical Sciences.

This work was supported by the Huffington Foundation and the National Institutes of Health (1F31NS118984-01, 1R01AG070934-01, NIH/AG058463, R35 NS132265/NINDS, and P30 AG066468).