A gut sense for a microbial pattern regulates feeding

• 成果类型: Article
• 署名作者: Liu, Winston W.; Reicher, Naama; Alway, Emily; Rupprecht, Laura E.; Weng, Peter; Schaefgen, Chloe; Klein, Marguerita E.; Villalobos, Jorge A.; Puerto-Hernandez, Carlos; Kiesling Altun, Yolanda Graciela; Carbajal, Amanda; Aguayo-Guerrero, Jose Alfredo; Coss, Alam; Sahasrabudhe, Atharva; Anikeeva, Polina; de Araujo, Alan; Bali, Avnika; de Lartigue, Guillaume; Gil-Lievana, Elvi; Gutierrez, Ranier; Miao, Edward A.; Rawls, John F.; Kaelberer, M. Maya; Bohorquez, Diego V.
• 署名单位: Duke University; Duke University; Duke University; Duke University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Monell Chemical Senses Center; University of Pennsylvania; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; Duke University; Duke University; Duke University; Duke University; University of Arizona; Duke University; Stanford University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-0942
• DOI: 10.1038/s41586-025-09301-7
• 发表日期: 2025-09-18
• 关键词: enteroendocrine cells; bacterial flagellin; metabolic syndrome; receptor; neurons; identification; secretion; pain; mice

摘要

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, 2, 3, 4-5. 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.