A gut sense for a microbial pattern regulates feeding

Winston W. Liu, Naama Reicher, Emily Alway, Laura E. Rupprecht, Peter Weng, Chloe Schaefgen, Marguerita E. Klein, Jorge A. Villalobos, Carlos Puerto-Hernandez, Yolanda Graciela Kiesling Altún, Amanda Carbajal, José Alfredo Aguayo-Guerrero, Alam Coss, Atharva Sahasrabudhe, Polina Anikeeva, Alan Araujo, Avnika Bali, Guillaume Lartigue, Elvi Gil-Lievana, Ranier Gutierrez, Edward A. Miao, John F. Rawls, M. Maya Kaelberer () and Diego V. Bohórquez ()
Additional contact information
Winston W. Liu: Duke University
Naama Reicher: Duke University
Emily Alway: Duke University
Laura E. Rupprecht: Duke University
Peter Weng: Duke University
Chloe Schaefgen: Duke University
Marguerita E. Klein: Duke University
Jorge A. Villalobos: Duke University
Carlos Puerto-Hernandez: Duke University
Yolanda Graciela Kiesling Altún: Duke University
Amanda Carbajal: Duke University
José Alfredo Aguayo-Guerrero: Duke University
Alam Coss: Duke University
Atharva Sahasrabudhe: Massachusetts Institute of Technology
Polina Anikeeva: Massachusetts Institute of Technology
Alan Araujo: Monell Chemical Senses Center
Avnika Bali: Monell Chemical Senses Center
Guillaume Lartigue: Monell Chemical Senses Center
Elvi Gil-Lievana: CINVESTAV
Ranier Gutierrez: CINVESTAV
Edward A. Miao: Duke University
John F. Rawls: Duke University
M. Maya Kaelberer: Duke University
Diego V. Bohórquez: Duke University

Nature, 2025, vol. 645, issue 8081, 729-736

Abstract: Abstract 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 choices1–5. 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 flagellin does not act on the nerve directly. Instead, flagellin stimulates neuropod cells from the colonic lumen to reduce feeding through a gut–brain sensory neural circuit. Moreover, flagellin reduces feeding independent of immune responses, metabolic changes or the presence of gut microbiota. This sense enables the host to adjust its behaviour in response to a molecular pattern from its resident microorganisms. We call this sense at the interface of the biota and the brain the neurobiotic sense7.

Date: 2025
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DOI: 10.1038/s41586-025-09301-7

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