Newly discovered ‘sixth sense’ links gut microbes to the brain in real time

(Press-News.org) by Shantell Kirkendoll

In a breakthrough that reimagines the way the gut and brain communicate, researchers have uncovered what they call a “neurobiotic sense,” a newly identified system that lets the brain respond in real time to signals from microbes living in our gut.

The new research, led by Duke University School of Medicine neuroscientists Diego Bohórquez, PhD, and M. Maya Kaelberer, PhD, and published in Nature, centers on neuropods, tiny sensor cells lining the colon’s epithelium. These cells detect a common microbial protein and send rapid messages to the brain that help curb appetite.

But this is just the beginning. The team believes this neurobiotic sense may be a broader platform for understanding how gut detects microbes, influencing everything from eating habits to mood — and even how the brain might shape the microbiome in return. 

“We were curious whether the body could sense microbial patterns in real time and not just as an immune or inflammatory response, but as a neural response that guides behavior in real time,” said Bohórquez, a professor of medicine and neurobiology at Duke University School of Medicine and senior author of the study.  

The key player is flagellin, an ancient protein found in bacterial flagella, a tail-like structure that bacteria use to swim. When we eat, some gut bacteria release flagellin. Neuropods detect it, with help from a receptor called TLR5, and fire off a message through the vagus nerve – a major communication line of communication between the gut and the brain.  

The team, supported by the National Institutes of Health, proposed a bold idea: that bacterial flagellin in the colon could trigger neuropods to send an appetite-suppressing signal to the brain — a direct microbial influence on behavior.

The researchers tested this by fasting mice overnight, then giving them a small dose of flagellin directly to the colon. Those mice ate less.  

When researchers tried the same experiment in mice missing the TLR5 receptor, nothing changed. The mice kept eating and gained weight, a clue that the pathway helps regulate appetite. The findings suggest that flagellin sends a “we’ve had enough” signal through TLR5, allowing the gut to tell the brain it’s time to stop eating. Without that receptor, the message doesn’t get through.

The discovery was guided by lead study authors Winston Liu, MD, PhD, Emily Alway, both graduate students of the Medical Scientist Training Program, and postdoctoral fellow Naama Reicher, Ph.D. Their experiments reveal that disrupting the pathway altered eating habits in mice pointed to a deeper link between gut microbes and behavior.

“Looking ahead, I think this work will be especially helpful for the broader scientific community to explain how our behavior is influenced by microbes,” said Bohórquez. “One clear next step is to investigate how specific diets change the microbial landscape in the gut. That could be a key piece of the puzzle in conditions like obesity or psychiatric disorders.”

Citation: “A gut sense for a microbial pattern regulates feeding,” Winston W. Liu et al., Nature, 23 July 2025 DOI: 10.1038/s41586-025-09301-7

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