{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:49:46Z","timestamp":1792810186649,"version":"4.5.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"8059","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2025,4,17]]},"DOI":"10.1038\/s41586-024-08581-9","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T11:03:33Z","timestamp":1739358213000},"page":"732-742","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Topological segregation of stress sensors along the gut crypt\u2013villus axis"],"prefix":"10.1038","volume":"640","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-9784","authenticated-orcid":false,"given":"Kouki K.","family":"Touhara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan D.","family":"Rossen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1997-4572","authenticated-orcid":false,"given":"Fei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tifany","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Garcia-Caraballo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Brizuela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-2825","authenticated-orcid":false,"given":"Jinhao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-0199","authenticated-orcid":false,"given":"Onur","family":"Cil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2527-2905","authenticated-orcid":false,"given":"Stuart M.","family":"Brierley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-9919","authenticated-orcid":false,"given":"Yulong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6365-4867","authenticated-orcid":false,"given":"David","family":"Julius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"8581_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1097\/MED.0b013e32835bc703","volume":"20","author":"MD Gershon","year":"2013","unstructured":"Gershon, M. D. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr. Opin. Endocrinol. Diabetes Obes. 20, 14\u201321 (2013).","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"8581_CR2","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/nrgastro.2013.105","volume":"10","author":"GM Mawe","year":"2013","unstructured":"Mawe, G. M. & Hoffman, J. M. Serotonin signalling in the gut functions, dysfunctions and therapeutic targets. Nat. Rev. Gastroenterol. Hepatol. 10, 473\u2013486 (2013).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"8581_CR3","doi-asserted-by":"publisher","first-page":"3408","DOI":"10.1073\/pnas.0805323106","volume":"106","author":"K Nozawa","year":"2009","unstructured":"Nozawa, K. et al. TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc. Natl Acad. Sci. USA 106, 3408\u20133413 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"8581_CR4","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.cell.2017.05.034","volume":"170","author":"NW Bellono","year":"2017","unstructured":"Bellono, N. W. et al. Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways. Cell 170, 185\u2013198 (2017).","journal-title":"Cell"},{"key":"8581_CR5","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.immuni.2020.10.014","volume":"54","author":"Z Chen","year":"2021","unstructured":"Chen, Z. et al. Interleukin-33 promotes serotonin release from enterochromaffin cells for intestinal homeostasis. Immunity 54, 151\u2013163 (2021).","journal-title":"Immunity"},{"key":"8581_CR6","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.molmet.2018.03.004","volume":"11","author":"ML Lund","year":"2018","unstructured":"Lund, M. L. et al. Enterochromaffin 5-HT cells\u2014a major target for GLP-1 and gut microbial metabolites. Mol. Metab. 11, 70\u201383 (2018).","journal-title":"Mol. Metab."},{"key":"8581_CR7","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1146\/annurev-physiol-021115-105439","volume":"78","author":"FM Gribble","year":"2016","unstructured":"Gribble, F. M. & Reimann, F. Enteroendocrine cells: chemosensors in the intestinal epithelium. Annu. Rev. Physiol. 78, 277\u2013299 (2016).","journal-title":"Annu. Rev. Physiol."},{"key":"8581_CR8","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1038\/169800b0","volume":"169","author":"V Erspamer","year":"1952","unstructured":"Erspamer, V. & Asero, B. Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-hydroxytryptamine. Nature 169, 800\u2013801 (1952).","journal-title":"Nature"},{"key":"8581_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15834-3","volume":"7","author":"PR Strege","year":"2017","unstructured":"Strege, P. R. et al. Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release. Sci. Rep. 7, 15650 (2017).","journal-title":"Sci. Rep."},{"key":"8581_CR10","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/978-3-031-05843-1_30","volume":"1383","author":"GM Mawe","year":"2022","unstructured":"Mawe, G. M., Hurd, M., Hennig, G. W. & Lavoie, B. Epithelial 5-HT4 receptors as a target for treating constipation and intestinal inflammation. Adv. Exp. Med. Biol. 1383, 329\u2013334 (2022).","journal-title":"Adv. Exp. Med. Biol."},{"key":"8581_CR11","doi-asserted-by":"publisher","first-page":"3615","DOI":"10.2174\/138161206778522029","volume":"12","author":"AJ Thompson","year":"2006","unstructured":"Thompson, A. J. & Lummis, S. C. 5-HT3 receptors. Curr. Pharm. Des. 12, 3615\u20133630 (2006).","journal-title":"Curr. Pharm. Des."},{"key":"8581_CR12","doi-asserted-by":"publisher","first-page":"4298","DOI":"10.1016\/j.cell.2022.10.001","volume":"185","author":"Z Xie","year":"2022","unstructured":"Xie, Z. et al. The gut-to-brain axis for toxin-induced defensive responses. Cell 185, 4298\u20134316 (2022).","journal-title":"Cell"},{"key":"8581_CR13","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41586-023-05829-8","volume":"616","author":"JR Bayrer","year":"2023","unstructured":"Bayrer, J. R. et al. Gut enterochromaffin cells drive visceral pain and anxiety. Nature 616, 137\u2013142 (2023).","journal-title":"Nature"},{"key":"8581_CR14","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2174\/1568007043482615","volume":"3","author":"J Bockaert","year":"2004","unstructured":"Bockaert, J., Claeysen, S., Compan, V. & Dumuis, A. 5-HT4 receptors. Curr. Drug Targets CNS Neurol. Disord. 3, 39\u201351 (2004).","journal-title":"Curr. Drug Targets CNS Neurol. Disord."},{"key":"8581_CR15","doi-asserted-by":"publisher","first-page":"e14589","DOI":"10.1111\/nmo.14589","volume":"35","author":"IR Tough","year":"2023","unstructured":"Tough, I. R., Lund, M. L., Patel, B. A., Schwartz, T. W. & Cox, H. M. Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine. Neurogastroenterol. Motil. 35, e14589 (2023).","journal-title":"Neurogastroenterol. Motil."},{"key":"8581_CR16","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1146\/annurev.physiol.62.1.535","volume":"62","author":"KE Barrett","year":"2000","unstructured":"Barrett, K. E. & Keely, S. J. Chloride secretion by the intestinal epithelium: molecular basis and regulatory aspects. Annu. Rev. Physiol. 62, 535\u2013572 (2000).","journal-title":"Annu. Rev. Physiol."},{"key":"8581_CR17","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nri3608","volume":"14","author":"LW Peterson","year":"2014","unstructured":"Peterson, L. W. & Artis, D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14, 141\u2013153 (2014).","journal-title":"Nat. Rev. Immunol."},{"key":"8581_CR18","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/s41556-018-0143-y","volume":"20","author":"J Beumer","year":"2018","unstructured":"Beumer, J. et al. Enteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient. Nat. Cell Biol. 20, 909\u2013916 (2018).","journal-title":"Nat. Cell Biol."},{"key":"8581_CR19","doi-asserted-by":"publisher","unstructured":"Song, Y. et al. Stratification of enterochromaffin cells by single-cell expression analysis. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2023.08.24.554649 (2023).","DOI":"10.1101\/2023.08.24.554649"},{"key":"8581_CR20","doi-asserted-by":"publisher","first-page":"e78512","DOI":"10.7554\/eLife.78512","volume":"12","author":"M Hayashi","year":"2023","unstructured":"Hayashi, M. et al. Enteroendocrine cell lineages that differentially control feeding and gut motility. eLife 12, e78512 (2023).","journal-title":"eLife"},{"key":"8581_CR21","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.autneu.2009.08.002","volume":"153","author":"PP Bertrand","year":"2010","unstructured":"Bertrand, P. P. & Bertrand, R. L. Serotonin release and uptake in the gastrointestinal tract. Auton. Neurosci. 153, 47\u201357 (2010).","journal-title":"Auton. Neurosci."},{"key":"8581_CR22","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/s41593-021-00823-7","volume":"24","author":"J Wan","year":"2021","unstructured":"Wan, J. et al. A genetically encoded sensor for measuring serotonin dynamics. Nat. Neurosci. 24, 746\u2013752 (2021).","journal-title":"Nat. Neurosci."},{"key":"8581_CR23","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/s41592-024-02188-8","volume":"21","author":"F Deng","year":"2024","unstructured":"Deng, F. et al. Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo. Nat. Methods 21, 692\u2013702 (2024).","journal-title":"Nat. Methods"},{"key":"8581_CR24","doi-asserted-by":"publisher","first-page":"33275","DOI":"10.1074\/jbc.M204935200","volume":"277","author":"BB Madison","year":"2002","unstructured":"Madison, B. B. et al. Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine. J. Biol. Chem. 277, 33275\u201333283 (2002).","journal-title":"J. Biol. Chem."},{"key":"8581_CR25","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/s41594-018-0116-7","volume":"25","author":"JD McCorvy","year":"2018","unstructured":"McCorvy, J. D. et al. Structural determinants of 5-HT2B receptor activation and biased agonism. Nat. Struct. Mol. Biol. 25, 787\u2013796 (2018).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"8581_CR26","doi-asserted-by":"publisher","unstructured":"Boj, S. F. et al. Forskolin-induced swelling in intestinal organoids: an in vitro assay for assessing drug response in cystic fibrosis patients. J. Vis. Exp. https:\/\/doi.org\/10.3791\/55159-v (2017).","DOI":"10.3791\/55159-v"},{"key":"8581_CR27","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.cell.2019.10.031","volume":"179","author":"L Bai","year":"2019","unstructured":"Bai, L. et al. Genetic identification of vagal sensory neurons that control feeding. Cell 179, 1129\u20131143 (2019).","journal-title":"Cell"},{"key":"8581_CR28","doi-asserted-by":"publisher","unstructured":"Fung, C. et al. Luminal nutrients activate distinct patterns in submucosal and myenteric neurons in the mouse small intestine. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2021.01.19.427232 (2021).","DOI":"10.1101\/2021.01.19.427232"},{"key":"8581_CR29","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41593-020-00736-x","volume":"24","author":"K Morarach","year":"2021","unstructured":"Morarach, K. et al. Diversification of molecularly defined myenteric neuron classes revealed by single-cell RNA sequencing. Nat. Neurosci. 24, 34\u201346 (2021).","journal-title":"Nat. Neurosci."},{"key":"8581_CR30","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/nature13552","volume":"512","author":"G Hassaine","year":"2014","unstructured":"Hassaine, G. et al. X-ray structure of the mouse serotonin 5-HT3 receptor. Nature 512, 276\u2013281 (2014).","journal-title":"Nature"},{"key":"8581_CR31","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.cell.2006.02.023","volume":"124","author":"DM Bautista","year":"2006","unstructured":"Bautista, D. M. et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124, 1269\u20131282 (2006).","journal-title":"Cell"},{"key":"8581_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/112_2013_11","volume":"164","author":"B Nilius","year":"2013","unstructured":"Nilius, B. & Appendino, G. Spices: the savory and beneficial science of pungency. Rev. Physiol. Biochem. Pharmacol. 164, 1\u201376 (2013).","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"8581_CR33","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.tox.2019.02.005","volume":"418","author":"RM LoPachin","year":"2019","unstructured":"LoPachin, R. M., Geohagen, B. C. & Nordstroem, L. U. Mechanisms of soft and hard electrophile toxicities. Toxicology 418, 62\u201369 (2019).","journal-title":"Toxicology"},{"key":"8581_CR34","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.taap.2017.03.007","volume":"324","author":"S Achanta","year":"2017","unstructured":"Achanta, S. & Jordt, S. E. TRPA1: acrolein meets its target. Toxicol. Appl. Pharmacol. 324, 45\u201350 (2017).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"8581_CR35","doi-asserted-by":"publisher","first-page":"e12717","DOI":"10.1111\/cmi.12717","volume":"19","author":"CL Hews","year":"2017","unstructured":"Hews, C. L. et al. The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo. Cell. Microbiol. 19, e12717 (2017).","journal-title":"Cell. Microbiol."},{"key":"8581_CR36","doi-asserted-by":"publisher","first-page":"7278","DOI":"10.1073\/pnas.1813020116","volume":"116","author":"SA Malaker","year":"2019","unstructured":"Malaker, S. A. et al. The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins. Proc. Natl Acad. Sci. USA 116, 7278\u20137287 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"8581_CR37","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/35079100","volume":"411","author":"AL Perraud","year":"2001","unstructured":"Perraud, A. L. et al. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411, 595\u2013599 (2001).","journal-title":"Nature"},{"key":"8581_CR38","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1093\/intimm\/dxh231","volume":"17","author":"N Miura","year":"2005","unstructured":"Miura, N. et al. Anti-CD3 induces bi-phasic apoptosis in murine intestinal epithelial cells: possible involvement of the Fas\/Fas ligand system in different T cell compartments. Int. Immunol. 17, 513\u2013522 (2005).","journal-title":"Int. Immunol."},{"key":"8581_CR39","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1097\/MIB.0b013e31829ecf4d","volume":"19","author":"A Linan-Rico","year":"2013","unstructured":"Linan-Rico, A. et al. Purinergic autocrine regulation of mechanosensitivity and serotonin release in a human EC model: ATP-gated P2X3 channels in EC are downregulated in ulcerative colitis. Inflamm. Bowel Dis. 19, 2366\u20132379 (2013).","journal-title":"Inflamm. Bowel Dis."},{"key":"8581_CR40","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.neuron.2021.11.027","volume":"110","author":"Z Wu","year":"2022","unstructured":"Wu, Z. et al. A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo. Neuron 110, 770\u2013782 (2022).","journal-title":"Neuron"},{"key":"8581_CR41","doi-asserted-by":"publisher","first-page":"G285","DOI":"10.1152\/ajpgi.00013.2019","volume":"317","author":"AM Harrington","year":"2019","unstructured":"Harrington, A. M. et al. Colonic afferent input and dorsal horn neuron activation differs between the thoracolumbar and lumbosacral spinal cord. Am. J. Physiol. Gastrointest. Liver Physiol. 317, G285\u2013G303 (2019).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"8581_CR42","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.chom.2020.05.004","volume":"28","author":"A Kumar","year":"2020","unstructured":"Kumar, A. et al. The serotonin neurotransmitter modulates virulence of enteric pathogens. Cell Host Microbe 28, 41\u201353 (2020).","journal-title":"Cell Host Microbe"},{"key":"8581_CR43","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1096\/fj.14-259598","volume":"29","author":"CS Reigstad","year":"2015","unstructured":"Reigstad, C. S. et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 29, 1395\u20131403 (2015).","journal-title":"FASEB J."},{"key":"8581_CR44","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/j.1600-079X.2010.00760.x","volume":"49","author":"PP Bertrand","year":"2010","unstructured":"Bertrand, P. P., Bertrand, R. L., Camello, P. J. & Pozo, M. J. Simultaneous measurement of serotonin and melatonin from the intestine of old mice: the effects of daily melatonin supplementation. J Pineal Res. 49, 23\u201334 (2010).","journal-title":"J Pineal Res."},{"key":"8581_CR45","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1039\/B611920D","volume":"132","author":"BA Patel","year":"2007","unstructured":"Patel, B. A., Bian, X., Quaiserov\u00e1-Mocko, V., Galligan, J. J. & Swain, G. M. In vitro continuous amperometric monitoring of 5-hydroxytryptamine release from enterochromaffin cells of the guinea pig ileum. Analyst 132, 41\u201347 (2007).","journal-title":"Analyst"},{"key":"8581_CR46","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41586-022-04615-2","volume":"606","author":"J Li","year":"2022","unstructured":"Li, J. et al. A tissue-like neurotransmitter sensor for the brain and gut. Nature 606, 94\u2013101 (2022).","journal-title":"Nature"},{"key":"8581_CR47","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41586-020-2480-9","volume":"585","author":"J Zhao","year":"2020","unstructured":"Zhao, J., Lin King, J. V., Paulsen, C. E., Cheng, Y. & Julius, D. Irritant-evoked activation and calcium modulation of the TRPA1 receptor. Nature 585, 141\u2013145 (2020).","journal-title":"Nature"},{"key":"8581_CR48","doi-asserted-by":"publisher","first-page":"eaat5236","DOI":"10.1126\/science.aat5236","volume":"361","author":"MM Kaelberer","year":"2018","unstructured":"Kaelberer, M. M. et al. A gut\u2013brain neural circuit for nutrient sensory transduction. Science 361, eaat5236 (2018).","journal-title":"Science"},{"key":"8581_CR49","doi-asserted-by":"publisher","first-page":"G523","DOI":"10.1152\/ajpgi.00019.2022","volume":"322","author":"KN Dodds","year":"2022","unstructured":"Dodds, K. N. et al. The gut\u2013brain axis: spatial relationship between spinal afferent nerves and 5-HT-containing enterochromaffin cells in mucosa of mouse colon. Am. J. Physiol. Gastrointest. Liver Physiol. 322, G523\u2013G533 (2022).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"8581_CR50","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s00441-024-03879-6","volume":"396","author":"NJ Spencer","year":"2024","unstructured":"Spencer, N. J., Kyloh, M. A., Travis, L. & Hibberd, T. J. Identification of vagal afferent nerve endings in the mouse colon and their spatial relationship with enterochromaffin cells. Cell Tissue Res. 396, 313\u2013327 (2024).","journal-title":"Cell Tissue Res."},{"key":"8581_CR51","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/jat.2550120504","volume":"12","author":"RA Parent","year":"1992","unstructured":"Parent, R. A., Caravello, H. E., Balmer, M. F., Shellenberger, T. E. & Long, J. E. One-year toxicity of orally administered acrolein to the beagle dog. J. Appl. Toxicol. 12, 311\u2013316 (1992).","journal-title":"J. Appl. Toxicol."},{"key":"8581_CR52","doi-asserted-by":"publisher","first-page":"e01947-17","DOI":"10.1128\/mBio.01947-17","volume":"9","author":"J Zhang","year":"2018","unstructured":"Zhang, J., Sturla, S., Lacroix, C. & Schwab, C. Gut microbial glycerol metabolism as an endogenous acrolein source. mBio 9, e01947-17 (2018).","journal-title":"mBio"},{"key":"8581_CR53","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1515\/fv-2016-0003","volume":"60","author":"L Tarabova","year":"2016","unstructured":"Tarabova, L., Makova, Z., Piesova, E., Szaboova, R. & Faixova, Z. Intestinal mucus layer and mucins (a review). Folia Vet. 60, 21\u201325 (2016).","journal-title":"Folia Vet."},{"key":"8581_CR54","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1007\/s12664-018-0890-5","volume":"37","author":"JK Limdi","year":"2018","unstructured":"Limdi, J. K. Dietary practices and inflammatory bowel disease. Indian J. Gastroenterol. 37, 284\u2013292 (2018).","journal-title":"Indian J. Gastroenterol."},{"key":"8581_CR55","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1136\/gutjnl-2020-322260","volume":"69","author":"P Paone","year":"2020","unstructured":"Paone, P. & Cani, P. D. Mucus barrier, mucins and gut microbiota: the expected slimy partners? Gut 69, 2232\u20132243 (2020).","journal-title":"Gut"},{"key":"8581_CR56","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1523\/JNEUROSCI.5369-07.2008","volume":"28","author":"DA Andersson","year":"2008","unstructured":"Andersson, D. A., Gentry, C., Moss, S. & Bevan, S. Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J. Neurosci. 28, 2485\u20132494 (2008).","journal-title":"J. Neurosci."},{"key":"8581_CR57","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1113\/jphysiol.2003.048587","volume":"554","author":"RA North","year":"2004","unstructured":"North, R. A. P2X3 receptors and peripheral pain mechanisms. J. Physiol. 554, 301\u2013308 (2004).","journal-title":"J. Physiol."},{"key":"8581_CR58","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/wmts.16","volume":"1","author":"G Burnstock","year":"2011","unstructured":"Burnstock, G. P2X receptors in the gut. WIREs Membr. Transp. Signal. 1, 269\u2013279 (2011).","journal-title":"WIREs Membr. Transp. Signal."},{"key":"8581_CR59","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1111\/bph.13428","volume":"174","author":"G Aviello","year":"2017","unstructured":"Aviello, G. & Knaus, U. G. ROS in gastrointestinal inflammation: rescue or sabotage? Br. J. Pharmacol. 174, 1704\u20131718 (2017).","journal-title":"Br. J. Pharmacol."},{"key":"8581_CR60","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41573-021-00268-4","volume":"21","author":"AP Koivisto","year":"2022","unstructured":"Koivisto, A. P., Belvisi, M. G., Gaudet, R. & Szallasi, A. Advances in TRP channel drug discovery: from target validation to clinical studies. Nat. Rev. Drug Discov. 21, 41\u201359 (2022).","journal-title":"Nat. Rev. Drug Discov."},{"key":"8581_CR61","doi-asserted-by":"publisher","first-page":"G495","DOI":"10.1152\/ajpgi.00036.2018","volume":"315","author":"Y Sei","year":"2018","unstructured":"Sei, Y. et al. Mature enteroendocrine cells contribute to basal and pathological stem cell dynamics in the small intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 315, G495\u2013G510 (2018).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"8581_CR62","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nature07935","volume":"459","author":"T Sato","year":"2009","unstructured":"Sato, T. et al. Single Lgr5 stem cells build crypt\u2013villus structures in vitro without a mesenchymal niche. Nature 459, 262\u2013265 (2009).","journal-title":"Nature"},{"key":"8581_CR63","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.14440\/jbm.2014.36","volume":"1","author":"AD Edelstein","year":"2014","unstructured":"Edelstein, A. D. et al. Advanced methods of microscope control using \u03bcManager software. J. Biol. Methods 1, e10 (2014).","journal-title":"J. Biol. Methods"},{"key":"8581_CR64","doi-asserted-by":"publisher","first-page":"e171249","DOI":"10.1172\/JCI171249","volume":"134","author":"L de Souza Goncalves","year":"2024","unstructured":"de Souza Goncalves, L. et al. Mg2+ supplementation treats secretory diarrhea in mice by activating calcium-sensing receptor in intestinal epithelial cells. J. Clin. Invest. 134, e171249 (2024).","journal-title":"J. Clin. Invest."},{"key":"8581_CR65","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1038\/nprot.2014.123","volume":"9","author":"R Tomer","year":"2014","unstructured":"Tomer, R., Ye, L., Hsueh, B. & Deisseroth, K. Advanced CLARITY for rapid and high-resolution imaging of intact tissues. Nat. Protoc. 9, 1682\u20131697 (2014).","journal-title":"Nat. Protoc."},{"key":"8581_CR66","doi-asserted-by":"publisher","first-page":"e121841","DOI":"10.1172\/jci.insight.121841","volume":"3","author":"L Grundy","year":"2018","unstructured":"Grundy, L. et al. Chronic linaclotide treatment reduces colitis-induced neuroplasticity and reverses persistent bladder dysfunction. JCI Insight 3, e121841 (2018).","journal-title":"JCI Insight"},{"key":"8581_CR67","doi-asserted-by":"publisher","first-page":"e25546","DOI":"10.1002\/cne.25546","volume":"532","author":"Q Wang","year":"2024","unstructured":"Wang, Q. et al. Comparative localization of colorectal sensory afferent central projections in the mouse spinal cord dorsal horn and caudal medulla dorsal vagal complex. J. Comp. Neurol. 532, e25546 (2024).","journal-title":"J. Comp. Neurol."},{"key":"8581_CR68","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1136\/gutjnl-2017-315631","volume":"68","author":"JRF Hockley","year":"2019","unstructured":"Hockley, J. R. F. et al. Single-cell RNAseq reveals seven classes of colonic sensory neuron. Gut 68, 633\u2013644 (2019).","journal-title":"Gut"},{"key":"8581_CR69","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1053\/j.gastro.2004.04.008","volume":"127","author":"SM Brierley","year":"2004","unstructured":"Brierley, S. M., Jones, R. C. 3rd, Gebhart, G. F. & Blackshaw, L. A. Splanchnic and pelvic mechanosensory afferents signal different qualities of colonic stimuli in mice. Gastroenterology 127, 166\u2013178 (2004).","journal-title":"Gastroenterology"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-024-08581-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-024-08581-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-024-08581-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T19:02:28Z","timestamp":1745175748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-024-08581-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":69,"journal-issue":{"issue":"8059","published-print":{"date-parts":[[2025,4,17]]}},"alternative-id":["8581"],"URL":"https:\/\/doi.org\/10.1038\/s41586-024-08581-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.02.06.579180","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]},"assertion":[{"value":"16 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"D.J. is a scientific advisor to Rapport Therapeutics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}