Gut Bacteria Imbalance After Stroke May Worsen Brain Inflammation todayheadline

An unexpected connection between gut microbes and brain recovery after stroke has caught the attention of researchers at UTHealth Houston, offering new insights into why some patients suffer more severe inflammation and poorer outcomes.

When stroke strikes, it triggers a cascade of changes throughout the body, including disruption of the delicate balance of bacteria in the gut. This imbalance may deprive the brain of crucial protective compounds that normally help regulate inflammation, according to findings published February 19 in Nature Communications.

The study identified a key protein called the aryl hydrocarbon receptor (AHR), which acts as a molecular sensor that responds to compounds from both the body and gut bacteria. After stroke, the researchers found a dramatic shift in this chemical balance—levels of beneficial bacteria-derived compounds plummeted while potentially harmful compounds produced by the body increased.

“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.”

In examining brain tissue from stroke patients, the researchers found elevated levels of AHR in microglia—the brain’s resident immune cells that coordinate inflammatory responses. When they supplemented aged mice with the beneficial bacterial compounds after inducing stroke, the animals showed reduced brain damage and better neurological function.

These findings align with a growing body of evidence connecting gut health to brain function. 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.

The researchers used both traditional mice and specialized germ-free mice that lack gut bacteria to pinpoint how these bacterial compounds affect brain inflammation. Without the beneficial bacterial compounds, immune cells in the brain showed altered inflammatory responses and increased markers of damage.

The study also revealed that aging worsens this bacterial imbalance after stroke, which may partly explain why older adults often experience poorer outcomes. Current stroke treatments focus primarily on restoring blood flow through clot-busting drugs or mechanical removal, but these options are available to fewer than 10% of patients due to timing constraints and other limitations.

“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.

The timing of these bacterial changes may offer a wider window for intervention, potentially helping patients who don’t qualify for current treatments.

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.

The study was supported by the Huffington Foundation and the National Institutes of Health.

The findings represent a step forward in understanding the complex relationship between gut health and brain recovery, potentially pointing to diet, probiotics, or metabolite supplementation as future areas for stroke recovery research.