The “Neurobiotic Sense”: How Gut Microbes Directly Influence Feeding

A Sixth Sense in the Gut: Microbes Controlling Appetite

For centuries, science has taught us about five senses. But new research suggests we may have another—one that links our gut microbes directly to our brain and feeding behavior.

Researchers from Duke University and collaborators have identified what they call the “neurobiotic sense”: a gut–brain sensory system that allows animals to detect microbial patterns in real time and adjust food intake accordingly

Flagellin: The Microbial Signal Behind Satiety

The study revealed that flagellin—a protein that makes up bacterial flagella—stimulates specialized gut cells known as neuropod cells. These cells, marked by the satiety hormone peptide YY (PYY), use the receptor Toll-like receptor 5 (TLR5) to sense flagellin.

When flagellin is present in the colon, neuropod cells release PYY, activating nearby vagal neurons via the NPY2R receptor. The signal travels rapidly to the brain, curbing food intake.

Strikingly, mice lacking TLR5 in these cells ate larger meals, gained more weight, and lost this microbial check on appetite.

Independent of Immune or Metabolic Signals

Unlike traditional TLR5 functions, which typically trigger immune responses, the study shows that this pathway works independently of inflammation or metabolism. It’s a direct sensory link between microbes in the colon and neurons that regulate feeding.

The researchers even coined a new term for this discovery: the neurobiotic sense—a sensory modality at the interface of the gut’s microbiota and the brain.

Why This Matters

This discovery reshapes our understanding of appetite regulation and opens new possibilities:

Obesity and metabolic disease: Targeting this gut–brain circuit could provide new therapies.
Gut microbiome science: Reveals that microbial “patterns,” not just metabolites, shape behavior.
Neuroscience: Expands the concept of sensory biology to include microbial signals.

Conclusion

Your gut isn’t just digesting food—it’s also sensing microbial signals and sending them straight to your brain. By uncovering this neurobiotic sense, researchers have added a completely new dimension to our understanding of hunger, satiety, and the role of our microbial partners in everyday behavior.

Reference

Liu, W. W., Reicher, N., Alway, E., Rupprecht, L. E., Weng, P., Schaefgen, C., … & Bohórquez, D. V. (2025). A gut sense for a microbial pattern regulates feeding. Nature, 1-8. https://doi.org/10.1038/s41586-025-09301-7