Scientists 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 the gut.
The research, published in Nature by a team at Duke University School of Medicine, describes how specialized cells in the colon detect a microbial protein and quickly relay messages to the brain to help curb appetite.
“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 senior author Diego Bohórquez, PhD, professor of medicine and neurobiology at Duke University School of Medicine.
The research was supported by the National Institutes of Health and other organizations. The authors disclosed that some of the findings have been filed as a provisional patent application and that two of the researchers are founders and board directors of the Gastronauts Foundation, a nonprofit organization.
The key player in this pathway is flagellin, an ancient protein found in bacterial flagella, which bacteria use to swim. When we eat, some gut bacteria release flagellin. Neuropods, tiny sensor cells lining the colon, detect it using a receptor called TLR5 and send a message to the brain via the vagus nerve, a major communication channel between the gut and the brain.
To test the mechanism, researchers gave a small dose of flagellin directly to the colon of mice that had been fasted overnight. Those mice ate less. But when the experiment was repeated in mice missing the TLR5 receptor, there was no change. The mice kept eating and gained weight, a clue that this pathway helps regulate appetite by sending a “we’ve had enough” signal to the brain.
The discovery was guided by lead study authors Winston Liu, MD, PhD; Emily Alway; and Naama Reicher, PhD. Their experiments reveal that disrupting the pathway altered eating habits in mice, pointing 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,” Bohórquez said. “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.”