biostudies-literatureLiu WWNCCIH NIH HHSNIDDK NIH HHSNIMH NIH HHS729-736https://www.ebi.ac.uk/biostudies/studies/S-EPMC12443592biostudies-literatureUnknown645(8081)To coexist with its resident microorganisms, the host must have a sense to adjust its behaviour in response to them. In the intestine, a sense for nutrients transduced to the brain through neuroepithelial circuits guides appetitive choices^1-5. However, a sense that allows the host to respond in real time to stimuli arising from resident gut microorganisms 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 (PYY)-labelled colonic neuropod cells. This stimulation leads to PYY release 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 flagelNatureA gut sense for a microbial pattern regulates feeding.PMC12443592R03 DK114500DP2 MH122402F32 DK139628F30 DK122712K01 DK138286F32 DK127757R01 DK132070F30 DK136229R21 AT010818R01 DK131112K01 DK131403F30 DK127650Kaelberer MMSchaefgen CKlein MEMiao EALiu WWVillalobos JAAnikeeva PCoss AAguayo-Guerrero JAWeng PSahasrabudhe AAlway Ede Araujo ABali Ade Lartigue GGil-Lievana EBohorquez DVRupprecht LEGutierrez RRawls JFKiesling Altun YGPuerto-Hernandez CCarbajal AReicher NfalseA gut sense for a microbial pattern regulates feeding.To coexist with its resident microorganisms, the host must have a sense to adjust its behaviour in response to them. In the intestine, a sense for nutrients transduced to the brain through neuroepithelial circuits guides appetitive choices^1-5. However, a sense that allows the host to respond in real time to stimuli arising from resident gut microorganisms 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 (PYY)-labelled colonic neuropod cells. This stimulation leads to PYY release 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 flagel2025-01-01T00:00:00Z2025 Sep2026-06-03T11:22:33.174Z2026-05-29T03:06:23.964ZS-EPMC124435924070219210.1038/s41586-025-09301-7