The neurobiotic sense
Liu WW, Reicher N, Alway E, Rupprecht LE, et al. A gut sense for a microbial pattern regulates feeding. Nature. 645, 729–736 (2025). DOI: https://doi.org/10.1038/s41586-025-09301-7
The colon is densely colonized by microorganisms, and those microorganisms are constantly shedding molecular patterns into the lumen. Whether the gut could sense those patterns, and whether that sensing could shape behavior, was unknown.
We discovered that it can. In the colon, a specialized class of epithelial cells bearing the neuromodulator PYY expresses TLR5, a receptor for flagellin: a protein found on the surface of bacteria across phyla. When flagellin enters the colon, it activates these cells, which release PYY onto vagal neurons and suppress feeding within minutes. Mice lacking TLR5 in these cells eat more and gain more weight than their littermates, not because of inflammation or metabolic dysfunction, but because a sensory circuit has gone quiet.
This circuit operates independently of the immune system, of circulating hormones, and even of the microbiome itself. It is a direct line from the bacteria in the gut to the brain. We call this the neurobiotic sense.
