Bertrand, P. P. The cornucopia of intestinal chemosensory transduction. Front. Neurosci. 3, 48 (2009).
Neunlist, M. & Schemann, M. Nutrient-induced changes in the phenotype and function of the enteric nervous system. J. Physiol. 592, 2959–2965 (2014).
Fung, C. & Vanden Berghe, P. Functional circuits and signal processing in the enteric nervous system. Cell. Mol. Life Sci. 77, 4505–4522 (2020).
Furness, J. B. The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroenterol. Hepatol. 9, 286–294 (2012).
Buchanan, K. L. et al. The preference for sugar over sweetener depends on a gut sensor cell. Nat. Neurosci. 25, 191–200 (2022).
Zhao, Q. et al. A multidimensional coding architecture of the vagal interoceptive system. Nature 603, 878–884 (2022).
Schemann, M. & Ehrlein, H. J. Postprandial patterns of canine jejunal motility and transit of luminal content. Gastroenterology 90, 991–1000 (1986).
Nocerino, A., Iafusco, M. & Guandalini, S. Cholera toxin-induced small intestinal secretion has a secretory effect on the colon of the rat. Gastroenterology 108, 34–39 (1995).
Fung, C., Ellis, M. & Bornstein, J. C. Luminal cholera toxin alters motility in isolated guinea-pig jejunum via a pathway independent of 5-HT3 receptors. Front. Neurosci. 4, 162 (2010).
Schneider, S., Wright, C. M. & Heuckeroth, R. O. Unexpected roles for the second brain: enteric nervous system as master regulator of bowel function. Annu. Rev. Physiol. 81, 235–259 (2019).
Spencer, N. J. & Hu, H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat. Rev. Gastroenterol. Hepatol. 17, 338–351 (2020).
Mercado-Perez, A. & Beyder, A. Gut feelings: mechanosensing in the gastrointestinal tract. Nat. Rev. Gastroenterol. Hepatol. 19, 283–296 (2022).
Alcaino, C. et al. A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release. Proc. Natl Acad. Sci. USA 115, E7632–E7641 (2018).
Furness, J. B., Rivera, L. R., Cho, H.-J., Bravo, D. M. & Callaghan, B. The gut as a sensory organ. Nat. Rev. Gastroenterol. Hepatol. 10, 729 (2013).
Husted, A. S., Trauelsen, M., Rudenko, O., Hjorth, S. A. & Schwartz, T. W. GPCR-mediated signaling of metabolites. Cell Metab. 25, 777–796 (2017).
Worthington, J. J., Reimann, F. & Gribble, F. M. Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity. Mucosal Immunol. 11, 3–20 (2018).
Lasrado, R. et al. Lineage-dependent spatial and functional organization of the mammalian enteric nervous system. Science 356, 722–726 (2017).
Song, Z. M., Brookes, S. J. & Costa, M. Identification of myenteric neurons which project to the mucosa of the guinea-pig small intestine. Neurosci. Lett. 129, 294–298 (1991).
Song, Z. M., Brookes, S. J., Steele, P. A. & Costa, M. Projections and pathways of submucous neurons to the mucosa of the guinea-pig small intestine. Cell Tissue Res. 269, 87–98 (1992).
Martin, A. M. et al. The nutrient-sensing repertoires of mouse enterochromaffin cells differ between duodenum and colon. Neurogastroenterol. Motil. 29, e13046 (2017).
Martin, A. M. et al. Regional differences in nutrient‐induced secretion of gut serotonin. Physiol. Rep. 5, e13199 (2017).
Gribble, F. M. & Reimann, F. Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nat. Rev. Endocrinol. 15, 226–237 (2019).
Rogers, G. J. et al. Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells. J. Physiol. 589, 1081–1093 (2011).
Bellono, N. W. et al. Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways. Cell 170, 185–198 (2017).
Mongardi Fantaguzzi, C., Thacker, M., Chiocchetti, R. & Furness, J. B. Identification of neuron types in the submucosal ganglia of the mouse ileum. Cell Tissue Res. 336, 179–189 (2009).
Qu, Z. D. et al. Immunohistochemical ***ysis of neuron types in the mouse small intestine. Cell Tissue Res. 334, 147–161 (2008).
Morarach, K. et al. Diversification of molecularly defined myenteric neuron cl***es revealed by single-cell RNA sequencing. Nat. Neurosci. 24, 34–46 (2021).
Liu, M., Seino, S. & Kirchgessner, A. L. Identification and characterization of glucoresponsive neurons in the enteric nervous system. J. Neurosci. 19, 10305 (1999).
Hao, M. M. et al. Development of the intrinsic innervation of the small bowel mucosa and villi. Am. J. Physiol. Gastrointest. Liver Physiol. 318, G53–G65 (2020).
Fung, C. et al. Luminal short chain fatty acids and 5-HT acutely activate myenteric neurons in the mouse proximal colon. Neurogastroenterol. Motil. 33, e14186 (2021).
Haber, A. L. et al. A single-cell survey of the small intestinal epithelium. Nature 551, 333–339 (2017).
Drokhlyansky, E. et al. The human and mouse enteric nervous system at single-cell resolution. Cell 182, 1606–1622 (2020).
Inoue, T. et al. Mizagliflozin, a novel selective SGLT1 inhibitor, exhibits potential in the amelioration of chronic constipation. Eur. J. Pharmacol. 806, 25–31 (2017).
Akalestou, E. et al. Intravital imaging of islet Ca2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice. Nat. Commun. 12, 5165 (2021).
Zhang, T., Perkins, M. H., Chang, H., Han, W. & de Araujo, I. E. An inter-organ neural circuit for appetite suppression. Cell 185, 2478–2494 (2022).
Gershon, M. D. & Tack, J. The serotonin signaling system: from basic understanding to drug development for functional gi disorders. Gastroenterology 132, 397–414 (2007).
Bertrand, P. P., Kunze, W. A., Bornstein, J. C., Furness, J. B. & Smith, M. L. Analysis of the responses of myenteric neurons in the small intestine to chemical stimulation of the mucosa. Am. J. Physiol. 273, G422–G435 (1997).
Bertrand, P. P., Kunze, W. A., Furness, J. B. & Bornstein, J. C. The terminals of myenteric intrinsic primary afferent neurons of the guinea-pig ileum are excited by 5-hydroxytryptamine acting at 5-hydroxytryptamine-3 receptors. Neuroscience 101, 459–469 (2000).
Cooke, H. J., Wunderlich, J. & Christofi, F. L. ‘The force be with you’: ATP in gut mechanosensory transduction. News Physiol. Sci. 18, 43–49 (2003).
Bertrand, P. P. & Bornstein, J. C. ATP as a putative sensory mediator: activation of intrinsic sensory neurons of the myenteric plexus via P2X receptors. Neuroscience 22, 4767–4775 (2002).
Vanden Berghe, P. et al. Neurochemical coding of myenteric neurons in the guinea-pig antrum. Cell Tissue Res. 297, 81–90 (1999).
Pan, H. & Gershon, M. D. Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine. J. Neurosci. 20, 3295–3309 (2000).
Mazzuoli-Weber, G. & Schemann, M. Mechanosensitivity in the enteric nervous system. Front. Cell. Neurosci. 9, 408 (2015).
Gershon, M. D. in The Enteric Nervous System II (eds Spencer, N. J. et al.) 307–318 (Springer, 2022).
Koo, A., Fothergill, L. J., Kuramoto, H. & Furness, J. B. 5-HT containing enteroendocrine cells characterised by morphologies, patterns of hormone co-expression, and relationships with nerve fibres in the mouse gastrointestinal tract. Histochem. Cell Biol. 155, 623–636 (2021).
Touhara, K. K. et al. Topological segregation of stress sensors along the gut crypt–villus axis. Nature 640, 732–742 (2025).
Su, C. Y., Menuz, K. & Carlson, J. R. Olfactory perception: receptors, cells, and circuits. Cell 139, 45–59 (2009).
Furness, J. B., Jones, C., Nurgali, K. & Clerc, N. Intrinsic primary afferent neurons and nerve circuits within the intestine. Prog. Neurobiol. 72, 143–164 (2004).
de Souza Melo, C. G. et al. Identification of intrinsic primary afferent neurons in mouse jejunum. Neurogastroenterol. Motil. 32, e13989 (2020).
Moore, B. A. & Vanner, S. Properties of synaptic inputs from myenteric neurons innervating submucosal S neurons in guinea pig ileum. Am. J. Physiol. Gastrointest. Liver Physiol. 278, G273–G280 (2000).
Monro, R. L., Bornstein, J. C. & Bertrand, P. P. Synaptic transmission from the submucosal plexus to the myenteric plexus in guinea-pig ileum. Neurogastroenterol. Motil. 20, 1165–1173 (2008).
Vanden Berghe, P. & Fung, C. in The Enteric Nervous System II (eds Spencer, N. J. et al) 71–79 (Springer, 2022).
Heanue, T. A., Shepherd, I. T. & Burns, A. J. Enteric nervous system development in avian and zebrafish models. Dev. Biol. 417, 129–138 (2016).
Zariwala, H. A. et al. A Cre-dependent GCaMP3 reporter mouse for neuronal imaging in vivo. J. Neurosci. 32, 3131–3141 (2012).
Danielian, P. S., Muccino, D., Rowitch, D. H., Michael, S. K. & McMahon, A. P. Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr. Biol. 8, 1323–1326 (1998).
el Marjou, F. et al. Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39, 186–193 (2004).
Vanden Berghe, P., Kenyon, J. L. & Smith, T. K. Mitochondrial Ca2+ uptake regulates the excitability of myenteric neurons. J. Neurosci. 22, 6962–6971 (2002).
Furness, J. B., Koopmans, H. S., Robbins, H. L. & Lin, H. C. Identification of intestinofugal neurons projecting to the coeliac and superior mesenteric ganglia in the rat. Auton. Neurosci. 83, 81–85 (2000).
Tan, L. L., Bornstein, J. C. & Anderson, C. R. The neurochemistry and innervation patterns of extrinsic sensory and sympathetic nerves in the myenteric plexus of the C57Bl6 mouse jejunum. Neuroscience 166, 564–579 (2010).
Timmermans, J.-P. et al. Occurrence, distribution and neurochemical features of small intestinal neurons projecting to the cranial mesenteric ganglion in the pig. Cell Tissue Res. 272, 49–58 (1993).
T***icker, B. C., Hennig, G. W., Costa, M. & Brookes, S. J. H. Rapid anterograde and retrograde tracing from mesenteric nerve trunks to the guinea-pig small intestine in vitro. Cell Tissue Res. 295, 437–452 (1999).
Preibisch, S., Saalfeld, S., Schindelin, J. & Tomancak, P. Software for bead-based registration of selective plane illumination microscopy data. Nat. Methods 7, 418–419 (2010).
Ventura, E. E., Davis, J. N. & Goran, M. I. Sugar content of popular sweetened beverages based on objective laboratory ***ysis: focus on fructose content. Obesity 19, 868–874 (2011).
Akiba, Y. et al. Short-chain fatty acid sensing in rat duodenum. J. Physiol. 593, 585–599 (2015).
Reitelseder, S. et al. Phenylalanine stable isotope tracer labeling of cow milk and meat and human experimental applications to study dietary protein-derived amino acid availability. Clin. Nutr. 39, 3652–3662 (2020).
Li, Z. et al. Regional complexity in enteric neuron wiring reflects diversity of motility patterns in the mouse large intestine. eLife 8, e42914 (2019).
Wang, Y. et al. Accurate quantification of astrocyte and neurotransmitter fluorescence dynamics for single-cell and population-level physiology. Nat. Neurosci. 22, 1936–1944 (2019).