A gut sense for a microbial pattern regulates feeding

ABSTRACT: To coexist with its microbes, the host must have a sense to adjust its behavior in response to them. In the intestine, a sense for nutrients transduced to the brain via neuroepithelial circuits guides appetitive choices1–5. However, a sense that allows to host to respond in real-time to stimuli arising from resident gut microbes remains to be uncovered. Here, we show that in the mouse colon, the ubiquitous microbial pattern flagellin—a unifying feature across phyla6—stimulates Toll-like receptor 5 (TLR5) in peptide YY-labeled colonic neuropod cells. This stimulation leads to the release of peptide YY onto NPY2R vagal nodose neurons to regulate feeding. Mice lacking TLR5 in these cells eat more and gain more weight than controls. We found that flagellin does not act on the nerve directly. Instead, flagellin stimulates neuropod cells from the colonic lumen to reduce feeding via a gut-brain sensory neural circuit. Moreover, the flagellin stimulus reduces feeding independent of immune responses, metabolic changes, or the presence of gut microbiota. The sensory modality described here enables a host to adjust its behavior by detecting a molecular pattern from its resident microbes. We call this sense at the interface of the biota and the brain, the neurobiotic sense.

ORGANISM(S): Mus musculus

PROVIDER: GSE288590 | GEO | 2025/05/08

REPOSITORIES: GEO