“Sixth sense”: Gut microbes tell brain to stop eating

Researchers have discovered a pathway between the gut microbes and the brain that can suppress appetite and, thereby, directly influence our behaviors. When cells in this pathway miss key receptors or if the pathway is disrupted in other aspects, microbes may not help signal the brain to stop eating, leading to a greater risk of chronic diseases like obesity. 

Published in Nature, the study focuses on tiny sensor cells called neuropods that line the colon. These cells detect a common microbial protein and send messages to the brain to help curb appetite.

Led by Duke University School of Medicine, US, neuroscientists, the team believes their breakthrough transforms understandings of how the gut and brain communicate. The new system enables the brain to respond to gut microbes in real-time. They call this a “neurobiotic sense.”

Researchers believe that the discovery of the neurotic sense is only the start of understanding how gut microbes influence humans’ eating, habits, and moods, and how the brain may shape the microbiome.

“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,” says senior author Diego Bohórquez, PhD, professor of medicine and neurobiology.

Flagellin to TLR5 pathway

The study explains the importance of a mechanism that works via flagellin, an ancient protein found in bacteria’s tail-like structure called flagella. 

During eating, some gut bacteria release flagellin, which neuropods can detect through the receptor TLR5.During eating, some gut bacteria release flagellin, which neuropods can detect through the receptor TLR5. It sends a signal through the vagus nerve, which is a major communication line between the gut and brain.

The researchers proposed that the bacterial flagellin in the colon might be able to trigger neuropods to signal appetite suppression to the brain, which would directly influence behavior.

In a test, mice given a small dose of flagellin directly into the colon ate less. However, when the same was tested on mice missing the TLR5 receptor, the mice continued eating and gained weight.

The test was used to show that flagellin sends the signal of feeling full through TLR5 in the gut, telling the brain it is time to stop eating.

“Looking ahead, I think this work will be especially helpful for the broader scientific community to explain how our behavior is influenced by microbes,” says 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.”

Gut-brain axis in headlines

In other gut science research, a prebiotic diet was suggested to boost brain GABA (gamma-aminobutyric acid) levels, a key neurotransmitter associated with calming effects and neurological health.

Another study suggested that combining synbiotic and “gut-directed” hypnotherapy significantly reduces gastrointestinal discomfort, irritability, and anxiety symptoms in autistic children.

Meanwhile, ZenGut, a natural microalgae extract developed by Microphyt, was recently found to “significantly improve” gut microbiota balance, relieve digestive discomfort, and enhance mood and mental well-being in healthy adults.