by University of Texas Health Science Center at Houston

Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-57014-2

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, Ph.D., 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.

More information: Pedram Peesh et al, Benefits of equilibrium between microbiota- and host-derived ligands of the aryl hydrocarbon receptor after stroke in aged male mice, Nature Communications (2025). DOI: 10.1038/s41467-025-57014-2

Journal information:Nature Communications

Provided by University of Texas Health Science Center at Houston

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