Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Bitter taste receptors as sensors of gut luminal contents

Nature Reviews Gastroenterology & Hepatology volume 22, pages 39–53 (2025)Cite this article

Subjects

Abstract

Taste is important in the selection of food and is orchestrated by a group of distinct receptors, the taste G protein-coupled receptors (GPCRs). Taste 1 receptors (Tas1rs in mice and TAS1Rs in humans; also known as T1Rs) detect sweet and umami tastes, and taste 2 receptors (Tas2rs in mice and TAS2Rs in humans; also known as T2Rs) detect bitterness. These receptors are also expressed in extraoral sites, including the gastrointestinal mucosa. Tas2rs/TAS2Rs have gained interest as potential targets to prevent or treat metabolic disorders. These bitter taste receptors are expressed in functionally distinct types of gastrointestinal mucosal cells, including enteroendocrine cells, which, upon stimulation, increase intracellular Ca2+ and release signalling molecules that regulate gut chemosensory processes critical for digestion and absorption of nutrients, for neutralization and expulsion of harmful substances, and for metabolic regulation. Expression of Tas2rs/TAS2Rs in gut mucosa is upregulated by high-fat diets, and intraluminal bitter ‘tastants’ affect gastrointestinal functions and ingestive behaviour through local and gut–brain axis signalling. Tas2rs/TAS2Rs are also found in Paneth and goblet cells, which release antimicrobial peptides and glycoproteins, and in tuft cells, which trigger type 2 immune response against parasites, thus providing a direct line of defence against pathogens. This Review will focus on gut Tas2r/TAS2R distribution, signalling and regulation in enteroendocrine cells, supporting their role as chemosensors of luminal content that serve distinct functions as regulators of body homeostasis and immune response.

Key points

  • Bitter taste receptors (type 2 taste receptors; Tas2rs/TAS2Rs) are G protein-coupled receptors (GPCRs) that detect bitter, potentially harmful substances, although bitterness does not predict toxicity and is not always aversive.

  • Functional genes exist for approximately 25 human bitter taste receptors (TAS2Rs) and ~36 rodent bitter taste receptors (Tas2rs); these genes detect a large number of natural and synthetic, structurally divergent compounds.

  • Tas2rs/TAS2Rs differ in their tuning broadness: some sense just a few or single ligands, and others are broadly tuned to recognize multiple tastants many of which activate multiple receptors.

  • Human TAS2Rs and mouse Tas2rs are found in many extraoral locations, where they serve various extragustatory functions, depending on the site of expression.

  • Multiple TAS2Rs/Tas2rs have been identified in the human and rodent gastrointestinal tract, where they are localized to distinct cell types, including enteroendocrine, goblet, Paneth and tuft cells.

  • Gut Tas2rs/TAS2Rs have been proposed as sensors of bile acids, bacteria, bacterial products, parasites and plant alkaloids; they might also serve as regulators of gut homeostasis in conditions of dysbiosis associated with obesity and metabolic syndrome and as defence mechanisms against infection.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Taste buds and the specialized cells that detect different tastes.
Fig. 2: Pathways involved in nutrient sensing by EECs.
Fig. 3: Schematic representation of EECs with neuropods.
Fig. 4: Cellular sites of expression of TAS2R38.
Fig. 5: Schematic illustration of Tas2r/TAS2R signalling in enteroendocrine cells.
Fig. 6: The putative functions of bitter taste receptor subtypes based on their known cellular localization and functional studies.

Similar content being viewed by others

References

  1. Chaudhari, N. & Roper, S. D. The cell biology of taste. J. Cell Biol. 190, 285–296 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Roper, S. D. Taste buds as peripheral chemosensory processors. Semin. Cell Dev. Biol. 24, 71–79 (2013).

    Article  CAS  PubMed  Google Scholar 

  3. Kinnamon, S. & Finger, T. The role of ATP and purinergic receptors in taste signaling. Handb. Exp. Pharmacol. 275, 91–107 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ma, Z., Tanis, J. E., Taruno, A. & Foskett, J. K. Calcium homeostasis modulator (CALHM) ion channels. Pflug. Arch. 468, 395–403 (2016).

    Article  CAS  Google Scholar 

  5. Taruno, A. et al. CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495, 223–226 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen, X., Gabitto, M., Peng, Y., Ryba, N. J. & Zuker, C. S. A gustotopic map of taste qualities in the mammalian brain. Science 333, 1262–1266 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Scott, T. R. & Verhagen, J. V. Taste as a factor in the management of nutrition. Nutrition 16, 874–885 (2000).

    Article  CAS  PubMed  Google Scholar 

  8. Nissim, I., Dagan-Wiener, A. & Niv, M. Y. The taste of toxicity: a quantitative analysis of bitter and toxic molecules. IUBMB Life 69, 938–946 (2017).

    Article  CAS  PubMed  Google Scholar 

  9. Glendinning, J. I. Is the bitter rejection response always adaptive? Physiol. Behav. 56, 1217–1227 (1994).

    Article  CAS  PubMed  Google Scholar 

  10. Reed, D. R. & Knaapila, A. Genetics of taste and smell: poisons and pleasures. Prog. Mol. Biol. Transl. Sci. 94, 213–240 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bartoshuk, L. M., Duffy, V. B. & Miller, I. J. PTC/PROP tasting: anatomy, psychophysics, and sex effects. Physiol. Behav. 56, 1165–1171 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Archer, N. et al. Obesity is associated with altered gene expression in human tastebuds. Int. J. Obes. 43, 1475–1484 (2019).

    Article  Google Scholar 

  13. Kaufman, A., Kim, J., Noel, C. & Dando, R. Taste loss with obesity in mice and men. Int. J. Obes. 44, 739–743 (2020).

    Article  CAS  Google Scholar 

  14. Ahart, Z. C. et al. Differential effects of diet and weight on taste responses in diet-induced obese mice. Obesity 28, 284–292 (2020).

    Article  CAS  PubMed  Google Scholar 

  15. Maliphol, A. B., Garth, D. J. & Medler, K. F. Diet-induced obesity reduces the responsiveness of the peripheral taste receptor cells. PLoS One 8, e79403 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chaudhari, N., Pereira, E. & Roper, S. D. Taste receptors for umami: the case for multiple receptors. Am. J. Clin. Nutr. 90, 738S–742S (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nelson, G. et al. Mammalian sweet taste receptors. Cell 106, 381–390 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Chandrashekar, J. et al. T2Rs function as bitter taste receptors. Cell 100, 703–711 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Wooding, S. P., Ramirez, V. A. & Behrens, M. Bitter taste receptors: genes, evolution and health. Evol. Med. Public Health 9, 431–447 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wu, S. V., Chen, M. C. & Rozengurt, E. Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat. Physiol. Genomics 22, 139–149 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. Rozengurt, N. et al. Co-localization of the α-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am. J. Physiol. Gastrointest. Liver Physiol. 291, G792–G802 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Lang, T., Di Pizio, A., Risso, D., Drayna, D. & Behrens, M. Activation profile of TAS2R2, the 26th human bitter taste receptor. Mol. Nutr. Food Res. 67, e2200775 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lossow, K. et al. Comprehensive analysis of mouse bitter taste receptors reveals different molecular receptive ranges for orthologous receptors in mice and humans. J. Biol. Chem. 291, 15358–15377 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Meyerhof, W. et al. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem. Senses 35, 157–170 (2010).

    Article  CAS  PubMed  Google Scholar 

  25. Dagan-Wiener, A. et al. BitterDB: taste ligands and receptors database in 2019. Nucleic Acids Res. 47, D1179–D1185 (2019).

    Article  PubMed  Google Scholar 

  26. Bayer, S. et al. Chemoinformatics view on bitter taste receptor agonists in food. J. Agric. Food Chem. 69, 13916–13924 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Di Pizio, A. & Niv, M. Y. Promiscuity and selectivity of bitter molecules and their receptors. Bioorg. Med. Chem. 23, 4082–4091 (2015).

    Article  PubMed  Google Scholar 

  28. Yang, M. Y., Kim, S. K., Kim, D., Liggett, S. B. & Goddard, W. A. 3rd. Structures and agonist binding sites of bitter taste receptor TAS2R5 complexed with Gi protein and validated against experiment. J. Phys. Chem. Lett. 12, 9293–9300 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim, Y. et al. Bitter taste receptor activation by cholesterol and an intracellular tastant. Nature 628, 664–671 (2024).

    Article  CAS  PubMed  Google Scholar 

  30. Hu, X. et al. Bitter taste TAS2R14 activation by intracellular tastants and cholesterol. Nature 631, 459–466 (2024).

    Article  CAS  PubMed  Google Scholar 

  31. Avau, B. & Depoortere, I. The bitter truth about bitter taste receptors: beyond sensing bitter in the oral cavity. Acta Physiol. 216, 407–420 (2016).

    Article  CAS  Google Scholar 

  32. Behrens, M. & Lang, T. Extra-oral taste receptors-function, disease, and perspectives. Front. Nutr. 9, 881177 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Behrens, M. & Meyerhof, W. Gustatory and extragustatory functions of mammalian taste receptors. Physiol. Behav. 105, 4–13 (2011).

    Article  CAS  PubMed  Google Scholar 

  34. Depoortere, I. Taste receptors of the gut: emerging roles in health and disease. Gut 63, 179–190 (2014).

    Article  CAS  PubMed  Google Scholar 

  35. Lee, S.-J., Depoortere, I. & Hatt, H. Therapeutic potential of ectopic olfactory and taste receptors. Nat. Rev. 18, 116–138 (2019).

    CAS  Google Scholar 

  36. Rozengurt, E. Taste receptors in the gastrointestinal tract. I. Bitter taste receptors and α-gustducin in the mammalian gut. Am. J. Physiol. Gastrointest. Liver Physiol. 291, G171–G177 (2006).

    Article  CAS  PubMed  Google Scholar 

  37. Sternini, C. Taste receptors in the gastrointestinal tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G457–G461 (2007).

    Article  PubMed  Google Scholar 

  38. Wang, Q., Liszt, K. I. & Depoortere, I. Extra-oral bitter taste receptors: new targets against obesity? Peptides 127, 170284 (2020).

    Article  CAS  PubMed  Google Scholar 

  39. Lu, P., Zhang, C. H., Lifshitz, L. M. & ZhuGe, R. Extraoral bitter taste receptors in health and disease. J. Gen. Physiol. 149, 181–197 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bakar, R., Reimann, F. & Gribble, F. M. The intestine as an endocrine organ and the role of gut hormones in metabolic regulation. Nat. Rev. Gastroenterol. Hepatol. 20, 784–796 (2023).

    Article  Google Scholar 

  41. 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, 729–740 (2013).

    Article  CAS  PubMed  Google Scholar 

  42. Steensels, S. & Depoortere, I. Chemoreceptors in the gut. Annu. Rev. Physiol. 80, 117–141 (2018).

    Article  CAS  PubMed  Google Scholar 

  43. Margolskee, R. F. et al. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc. Natl Acad. Sci. USA 104, 15075–15080 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Young, R. L. et al. Disordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes. Diabetes 62, 3532–3541 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gorboulev, V. et al. Na+-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61, 187–196 (2012).

    Article  CAS  PubMed  Google Scholar 

  46. Gribble, F. M., Williams, L., Simpson, A. K. & Reimann, F. A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line. Diabetes 52, 1147–1154 (2003).

    Article  CAS  PubMed  Google Scholar 

  47. Kuhre, R. E., Frost, C. R., Svendsen, B. & Holst, J. J. Molecular mechanisms of glucose-stimulated GLP-1 secretion from perfused rat small intestine. Diabetes 64, 370–382 (2015).

    Article  CAS  PubMed  Google Scholar 

  48. Sternini, C., Anselmi, L. & Rozengurt, E. Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing. Curr. Opin. Endocrinol. Diabetes Obes. 15, 73–78 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ye, L. et al. Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways. Cell Host Microbe 29, 179–196.e9 (2021).

    Article  CAS  PubMed  Google Scholar 

  50. Latorre, R., Sternini, C., De Giorgio, R. & Greenwood-Van Meerveld, B. Enteroendocrine cells: a review of their role in brain-gut communication. Neurogastroenterol. Motil. 28, 620–630 (2016).

    Article  CAS  PubMed  Google Scholar 

  51. Liddle, R. A. Interactions of gut endocrine cells with epithelium and neurons. Compr. Physiol. 8, 1019–1030 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Gerbe, F., Legraverend, C. & Jay, P. The intestinal epithelium tuft cells: specification and function. Cell Mol. Life Sci. 69, 2907–2917 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Howitt, M. R. et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351, 1329–1333 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Janssen, S. & Depoortere, I. Nutrient sensing in the gut: new roads to therapeutics? Trends Endocrinol. Metab. 24, 92–100 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. Psichas, A., Reimann, F. & Gribble, F. M. Gut chemosensing mechanisms. J. Clin. Invest. 125, 908–917 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Bohorquez, D. V., Chandra, R., Samsa, L. A., Vigna, S. R. & Liddle, R. A. Characterization of basal pseudopod-like processes in ileal and colonic PYY cells. J. Mol. Histol. 42, 3–13 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Bohorquez, D. V. & Liddle, R. A. Axon-like basal processes in enteroendocrine cells: characteristics and potential targets. Clin. Transl. Sci. 4, 387–391 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Liddle, R. A. Neuropods. Cell Mol. Gastroenterol. Hepatol. 7, 739–747 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Bohorquez, D. V. et al. An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy. PLoS One 9, e89881 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Kaelberer, M. M., Rupprecht, L. E., Liu, W. W., Weng, P. & Bohorquez, D. V. Neuropod cells: the emerging biology of gut-brain sensory transduction. Annu. Rev. Neurosci. 43, 337–353 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kaelberer, M. M. et al. A gut-brain neural circuit for nutrient sensory transduction. Science 361, eaat5236 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Bezencon, C., le Coutre, J. & Damak, S. Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem. Senses 32, 41–49 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Hofer, D. & Drenckhahn, D. Identification of the taste cell G-protein, α-gustducin, in brush cells of the rat pancreatic duct system. Histochem. Cell Biol. 110, 303–309 (1998).

    Article  CAS  PubMed  Google Scholar 

  64. Hofer, D., Puschel, B. & Drenckhahn, D. Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc. Natl Acad. Sci. USA 93, 6631–6634 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sutherland, K., Young, R. L., Cooper, N. J., Horowitz, M. & Blackshaw, L. A. Phenotypic characterization of taste cells of the mouse intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G1420–G1428 (2007).

    Article  CAS  PubMed  Google Scholar 

  66. Wu, S. V. et al. Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc. Natl Acad. Sci. USA 99, 2392–2397 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Latorre, R. et al. Enteroendocrine profile of α-transducin immunoreactive cells in the gastrointestinal tract of the European sea bass (Dicentrarchus labrax). Fish Physiol. Biochem. 39, 1555–1565 (2013).

    Article  CAS  PubMed  Google Scholar 

  68. Mazzoni, M. et al. Expression and regulation of α-transducin in the pig gastrointestinal tract. J. Cell Mol. Med. 17, 466–474 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mazzoni, M. et al. Distribution of α-transducin and α-gustducin immunoreactive cells in the chicken (Gallus domesticus) gastrointestinal tract. Poult. Sci. 95, 1624–1630 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Janssen, S. et al. Bitter taste receptors and a-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc. Natl Acad. Sci. USA 108, 2094–2099 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. De Giorgio, R. et al. Regulation of α-transducin and α-gustducin expression by a high protein diet in the pig gastrointestinal tract. PLoS One 11, e0148954 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Gaida, M. M. et al. Expression of the bitter receptor T2R38 in pancreatic cancer: localization in lipid droplets and activation by a bacteria-derived quorum-sensing molecule. Oncotarget 7, 12623–12632 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Liszt, K. I. et al. Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells. Proc. Natl Acad. Sci. USA 114, E6260–E6269 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Le Neve, B., Foltz, M., Daniel, H. & Gouka, R. The steroid glycoside H.g.-12 from Hoodia gordonii activates the human bitter receptor TAS2R14 and induces CCK release from HuTu-80 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G1368–G1375 (2010).

    Article  PubMed  Google Scholar 

  75. Gu, F. et al. Bitter taste receptor mTas2r105 is expressed in small intestinal villus and crypts. Biochem. Biophys. Res. Commun. 463, 934–941 (2015).

    Article  CAS  PubMed  Google Scholar 

  76. Prandi, S., Voigt, A., Meyerhof, W. & Behrens, M. Expression profiling of Tas2r genes reveals a complex pattern along the mouse GI tract and the presence of Tas2r131 in a subset of intestinal Paneth cells. Cell Mol. Life Sci. 75, 49–65 (2018).

    Article  CAS  PubMed  Google Scholar 

  77. Kurtz, R., Steinberg, L. G., Betcher, M., Fowler, D. & Shepard, B. D. The sensing liver: localization and ligands for hepatic murine olfactory and taste receptors. Front. Physiol. 11, 574082 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Vegezzi, G. et al. Diet-induced regulation of bitter taste receptor subtypes in the mouse gastrointestinal tract. PLoS One 9, e107732 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Caremoli, F. et al. Microbiota-dependent upregulation of bitter taste receptor subtypes in the mouse large intestine in high-fat diet-induced obesity. Nutrients 15, 4145 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Jeon, T. I., Zhu, B., Larson, J. L. & Osborne, T. F. SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice. J. Clin. Invest. 118, 3693–3700 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Latorre, R. et al. Expression of the bitter taste receptor, T2R38, in enteroendocrine cells of the colonic mucosa of overweight/obese vs. lean subjects. PLoS One 11, e0147468 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Kok, B. P. et al. Intestinal bitter taste receptor activation alters hormone secretion and imparts metabolic benefits. Mol. Metab. 16, 76–87 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Hayashi, M. et al. Expression of TAS2R14 in the intestinal endocrine cells of non-human primates. Genes Genomics 43, 259–267 (2021).

    Article  CAS  PubMed  Google Scholar 

  84. Widmayer, P. et al. Distinct cell types with the bitter receptor Tas2r126 in different compartments of the stomach. Front. Physiol. 11, 32 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Prandi, S. et al. A subset of mouse colonic goblet cells expresses the bitter taste receptor Tas2r131. PLoS One 8, e82820 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Liszt, K. I. et al. Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity. J. Clin. Invest. 132, e144828 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Chen, M. C., Wu, V., Reeve, J. R. & Rozengurt, E. Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels. Am. J. Physiol. Cell Physiol. 291, C726–C739 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Jang, H. J. et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc. Natl Acad. Sci. USA 104, 15069–15074 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Luo, X. C. et al. Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells. Proc. Natl Acad. Sci. USA 116, 5564–5569 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Masuho, I., Tateyama, M. & Saitoh, O. Characterization of bitter taste responses of intestinal STC-1 cells. Chem. Senses 30, 281–290 (2005).

    Article  CAS  PubMed  Google Scholar 

  91. Catterall, W. A., Striessnig, J., Snutch, T. P. & Perez-Reyes, E. International Union of Pharmacology. XL. Compendium of voltage-gated ion channels: calcium channels. Pharmacol. Rev. 55, 579–581 (2003).

    Article  CAS  PubMed  Google Scholar 

  92. Mangel, A. W., Scott, L. & Liddle, R. A. Depolarization-stimulated cholecystokinin secretion is mediated by L-type calcium channels in STC-1 cells. Am. J. Physiol. 270, G287–G290 (1996).

    CAS  PubMed  Google Scholar 

  93. Prawitt, D. et al. TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proc. Natl Acad. Sci. USA 100, 15166–15171 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Dutta Banik, D., Martin, L. E., Freichel, M., Torregrossa, A. M. & Medler, K. F. TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells. Proc. Natl Acad. Sci. USA 115, E772–E781 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Shah, B. P., Liu, P., Yu, T., Hansen, D. R. & Gilbertson, T. A. TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1. Am. J. Physiol. Cell Physiol. 302, C210–C219 (2012).

    Article  CAS  PubMed  Google Scholar 

  96. Lu, V. B. et al. Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons. Nat. Commun. 10, 1029 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Moran, T. H. Gut peptides in the control of food intake. Int. J. Obes. 33, S7–S10 (2009).

    Article  CAS  Google Scholar 

  98. Toshinai, K. et al. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem. Biophys. Res. Commun. 281, 1220–1225 (2001).

    Article  CAS  PubMed  Google Scholar 

  99. Lee, R. J. et al. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J. Clin. Invest. 122, 4145–4159 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Lee, R. J., Chen, B., Redding, K. M., Margolskee, R. F. & Cohen, N. A. Mouse nasal epithelial innate immune responses to Pseudomonas aeruginosa quorum-sensing molecules require taste signaling components. Innate Immun. 20, 606–617 (2014).

    Article  PubMed  Google Scholar 

  101. Tizzano, M., Cristofoletti, M., Sbarbati, A. & Finger, T. E. Expression of taste receptors in solitary chemosensory cells of rodent airways. BMC Pulm. Med. 11, 3 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Tizzano, M. et al. Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc. Natl Acad. Sci. USA 107, 3210–3215 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Cooley, M., Chhabra, S. R. & Williams, P. N-Acylhomoserine lactone-mediated quorum sensing: a twist in the tail and a blow for host immunity. Chem. Biol. 15, 1141–1147 (2008).

    Article  CAS  PubMed  Google Scholar 

  104. Deep, A., Chaudhary, U. & Gupta, V. Quorum sensing and bacterial pathogenicity: from molecules to disease. J. Lab. Physicians 3, 4–11 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Sbarbati, A. et al. Acyl homoserine lactones induce early response in the airway. Anat. Rec. 292, 439–448 (2009).

    Article  Google Scholar 

  106. Kendall, M. M. & Sperandio, V. Quorum sensing by enteric pathogens. Curr. Opin. Gastroenterol. 23, 10–15 (2007).

    Article  PubMed  Google Scholar 

  107. Rubio-Gomez, J. M. et al. Full transcriptomic response of Pseudomonas aeruginosa to an inulin-derived fructooligosaccharide. Front. Microbiol. 11, 202 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Huynh, J. et al. Bitter taste receptor T2R138 in mouse enteroendocrine cells is a sensor for the quorum sensing molecule, acyl-homoserine lactone. Gastroenterology 152, S823 (2017).

    Article  Google Scholar 

  109. Greene, T. A. et al. Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One 6, e20123 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Kohl, S., Behrens, M., Dunkel, A., Hofmann, T. & Meyerhof, W. Amino acids and peptides activate at least five members of the human bitter taste receptor family. J. Agric. Food Chem. 61, 53–60 (2013).

    Article  CAS  PubMed  Google Scholar 

  111. Schaefer, S. et al. Membrane-bound chemoreception of bitter bile acids and peptides is mediated by the same subset of bitter taste receptors. Cell Mol. Life Sci. 81, 217 (2024).

    Article  CAS  PubMed  Google Scholar 

  112. Ziegler, F., Steuer, A., Di Pizio, A. & Behrens, M. Physiological activation of human and mouse bitter taste receptors by bile acids. Commun. Biol. 6, 612 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Albaugh, V. L. et al. Role of bile acids and GLP-1 in mediating the metabolic improvements of bariatric surgery. Gastroenterology 156, 1041–1051.e4 (2019).

    Article  CAS  PubMed  Google Scholar 

  114. Behrens, M., Di Pizio, A., Redel, U., Meyerhof, W. & Korsching, S. I. At the root of T2R gene evolution: recognition profiles of coelacanth and zebrafish bitter receptors. Genome Biol. Evol. 13, evaa264 (2021).

    Article  PubMed  Google Scholar 

  115. Rezaie, P., Bitarafan, V., Horowitz, M. & Feinle-Bisset, C. Effects of bitter substances on GI function, energy intake and glycaemia — do preclinical findings translate to outcomes in humans? Nutrients 13, 1317 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Xie, C. et al. Role of intestinal bitter sensing in enteroendocrine hormone secretion and metabolic control. Front. Endocrinol. 9, 576 (2018).

    Article  Google Scholar 

  117. Pham, H. et al. A bitter pill for type 2 diabetes? The activation of bitter taste receptor TAS2R38 can stimulate GLP-1 release from enteroendocrine L-cells. Biochem. Biophys. Res. Commun. 475, 295–300 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Steinert, R. E., Beglinger, C. & Langhans, W. Intestinal GLP-1 and satiation: from man to rodents and back. Int. J. Obes. 40, 198–205 (2016).

    Article  CAS  Google Scholar 

  119. Muller, T. D. et al. Glucagon-like peptide 1 (GLP-1). Mol. Metab. 30, 72–130 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Deacon, C. F., Mannucci, E. & Ahren, B. Glycaemic efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors as add-on therapy to metformin in subjects with type 2 diabetes — a review and meta analysis. Diabetes Obes. Metab. 14, 762–767 (2012).

    Article  CAS  PubMed  Google Scholar 

  121. Drucker, D. J. & Nauck, M. A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368, 1696–1705 (2006).

    Article  CAS  PubMed  Google Scholar 

  122. Phillips, A. & Clements, J. N. Clinical review of subcutaneous semaglutide for obesity. J. Clin. Pharm. Ther. 47, 184–193 (2022).

    Article  PubMed  Google Scholar 

  123. Park, J. et al. GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell. Biochem. Biophys. Res. Commun. 468, 306–311 (2015).

    Article  CAS  PubMed  Google Scholar 

  124. Dotson, C. D. et al. Bitter taste receptors influence glucose homeostasis. PLoS One 3, e3974 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Kim, K. H. et al. Cucurbitacin B induces hypoglycemic effect in diabetic mice by regulation of AMP-activated protein kinase alpha and glucagon-like peptide-1 via bitter taste receptor signaling. Front. Pharmacol. 9, 1071 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Kim, K. S., Egan, J. M. & Jang, H. J. Denatonium induces secretion of glucagon-like peptide-1 through activation of bitter taste receptor pathways. Diabetologia 57, 2117–2125 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Saltiel, M. Y. et al. Sweet taste receptor activation in the gut is of limited importance for glucose-stimulated GLP-1 and GIP secretion. Nutrients 9, 418 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Di Pizio, A., Ben Shoshan-Galeczki, Y., Hayes, J. E. & Niv, M. Y. Bitter and sweet tasting molecules: It’s complicated. Neurosci. Lett. 700, 56–63 (2019).

    Article  PubMed  Google Scholar 

  129. Wang, Q. et al. Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut. FASEB J. 33, 4907–4920 (2019).

    Article  CAS  PubMed  Google Scholar 

  130. Tschop, M. et al. Circulating ghrelin levels are decreased in human obesity. Diabetes 50, 707–709 (2001).

    Article  CAS  PubMed  Google Scholar 

  131. Lee, R. J. et al. Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J. Clin. Invest. 124, 1393–1405 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Gershon, M. D. Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel. Aliment. Pharmacol. Ther. 13, 15–30 (1999).

    Article  PubMed  Google Scholar 

  133. Kaji, I., Karaki, S., Fukami, Y., Terasaki, M. & Kuwahara, A. Secretory effects of a luminal bitter tastant and expressions of bitter taste receptors, T2Rs, in the human and rat large intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G971–G981 (2009).

    Article  CAS  PubMed  Google Scholar 

  134. Glendinning, J. I., Yiin, Y. M., Ackroff, K. & Sclafani, A. Intragastric infusion of denatonium conditions flavor aversions and delays gastric emptying in rodents. Physiol. Behav. 93, 757–765 (2008).

    Article  CAS  PubMed  Google Scholar 

  135. Kim, Y. S. & Ho, S. B. Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr. Gastroenterol. Rep. 12, 319–330 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  136. McGuckin, M. A., Linden, S. K., Sutton, P. & Florin, T. H. Mucin dynamics and enteric pathogens. Nat. Rev. Microbiol. 9, 265–278 (2011).

    Article  CAS  PubMed  Google Scholar 

  137. Clevers, H. C. & Bevins, C. L. Paneth cells: maestros of the small intestinal crypts. Annu. Rev. Physiol. 75, 289–311 (2013).

    Article  CAS  PubMed  Google Scholar 

  138. Vaishnava, S., Behrendt, C. L., Ismail, A. S., Eckmann, L. & Hooper, L. V. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc. Natl Acad. Sci. USA 105, 20858–20863 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Gerbe, F. et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529, 226–230 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Nadjsombati, M. S. et al. Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit. Immunity 49, 33–41.e7 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Haber, A. L. et al. A single-cell survey of the small intestinal epithelium. Nature 551, 333–339 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Kratz, C. M., Levitsky, D. A. & Lustick, S. L. Long term effects of quinine on food intake and body weight in the rat. Physiol. Behav. 21, 321–324 (1978).

    Article  CAS  PubMed  Google Scholar 

  143. Leng, S. H., Lu, F. E. & Xu, L. J. Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacol. Sin. 25, 496–502 (2004).

    CAS  PubMed  Google Scholar 

  144. van Heerden, F. R. et al. An appetite suppressant from Hoodia species. Phytochemistry 68, 2545–2553 (2007).

    Article  PubMed  Google Scholar 

  145. Nauck, M. A. et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 741–744 (1993).

    Article  CAS  PubMed  Google Scholar 

  146. Yajima, H. et al. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor α and γ and reduce insulin resistance. J. Biol. Chem. 279, 33456–33462 (2004).

    Article  CAS  PubMed  Google Scholar 

  147. Andreozzi, P. et al. The bitter taste receptor agonist quinine reduces calorie intake and increases the postprandial release of cholecystokinin in healthy subjects. J. Neurogastroenterol. Motil. 21, 511–519 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Iven, J. et al. Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms. Nutr. Neurosci. 22, 850–862 (2019).

    Article  CAS  PubMed  Google Scholar 

  149. Bitarafan, V. et al. Intragastric administration of the bitter tastant quinine lowers the glycemic response to a nutrient drink without slowing gastric emptying in healthy men. Am. J. Physiol. Regul. Integr. Comp. Physiol. 318, R263–R273 (2020).

    Article  CAS  PubMed  Google Scholar 

  150. Bitarafan, V. et al. Effects of intraduodenal infusion of the bitter tastant, quinine, on antropyloroduodenal motility, plasma cholecystokinin, and energy intake in healthy men. J. Neurogastroenterol. Motil. 25, 413–422 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Deloose, E. et al. Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers. Am. J. Clin. Nutr. 105, 580–588 (2017).

    Article  CAS  PubMed  Google Scholar 

  152. van Avesaat, M. et al. Intraduodenal infusion of a combination of tastants decreases food intake in humans. Am. J. Clin. Nutr. 102, 729–735 (2015).

    Article  PubMed  Google Scholar 

  153. Huang, T. N., Lu, K. N., Pai, Y. P., Chin, H. & Huang, C. J. Role of GLP-1 in the hypoglycemic effects of wild bitter gourd. Evid. Based Complement. Altern. Med. 2013, 625892 (2013).

    Article  Google Scholar 

  154. Suh, H. W. et al. A bitter herbal medicine Gentiana scabra root extract stimulates glucagon-like peptide-1 secretion and regulates blood glucose in db/db mouse. J. Ethnopharmacol. 172, 219–226 (2015).

    Article  PubMed  Google Scholar 

  155. Rose, B. D. et al. Comparative effects of intragastric and intraduodenal administration of quinine on the plasma glucose response to a mixed-nutrient drink in healthy men: relations with glucoregulatory hormones and gastric emptying. J. Nutr. 151, 1453–1461 (2021).

    Article  CAS  PubMed  Google Scholar 

  156. Mennella, I. et al. Microencapsulated bitter compounds (from Gentiana lutea) reduce daily energy intakes in humans. Br. J. Nutr. 116, 1841–1850 (2016).

    Article  CAS  PubMed  Google Scholar 

  157. Niethammer, A., Zheng, Z., Timmer, A. & Lee, T.-L. First-in-human evaluation of oral denatonium acetate (ARD-101), a potential bitter taste receptor agonist: a randomized, double-blind, placebo-controlled phase 1 trial in healthy adults. Clin. Pharmacol. Drug Dev. 11, 997–1006 (2022).

    Article  CAS  PubMed  Google Scholar 

  158. Behrens, M., Foerster, S., Staehler, F., Raguse, J. D. & Meyerhof, W. Gustatory expression pattern of the human TAS2R bitter receptor gene family reveals a heterogenous population of bitter responsive taste receptor cells. J. Neurosci. 27, 12630–12640 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Lu, P. et al. Genetic deletion of the Tas2r143/Tas2r135/Tas2r126 cluster reveals that TAS2Rs may not mediate bitter tastant-induced bronchodilation. J. Cell Physiol. 236, 6407–6423 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Zhang, C. H. et al. The cellular and molecular basis of bitter tastant-induced bronchodilation. PLoS Biol. 11, e1001501 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Bufe, B. et al. The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr. Biol. 15, 322–327 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Kim, U., Wooding, S., Ricci, D., Jorde, L. B. & Drayna, D. Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci. Hum. Mutat. 26, 199–204 (2005).

    Article  CAS  PubMed  Google Scholar 

  163. Soranzo, N. et al. Positive selection on a high-sensitivity allele of the human bitter-taste receptor TAS2R16. Curr. Biol. 15, 1257–1265 (2005).

    Article  CAS  PubMed  Google Scholar 

  164. Ueda, T. et al. Identification of coding single-nucleotide polymorphisms in human taste receptor genes involving bitter tasting. Biochem. Biophys. Res. Commun. 285, 147–151 (2001).

    Article  CAS  PubMed  Google Scholar 

  165. Roudnitzky, N. et al. Copy number variation in TAS2R bitter taste receptor genes: structure, origin, and population genetics. Chem. Senses 41, 649–659 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Dotson, C. D., Shaw, H. L., Mitchell, B. D., Munger, S. D. & Steinle, N. I. Variation in the gene TAS2R38 is associated with the eating behavior disinhibition in Old Order Amish women. Appetite 54, 93–99 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Tepper, B. J. Nutritional implications of genetic taste variation: the role of PROP sensitivity and other taste phenotypes. Annu. Rev. Nutr. 28, 367–388 (2008).

    Article  CAS  PubMed  Google Scholar 

  168. Behrens, M., Gunn, H. C., Ramos, P. C., Meyerhof, W. & Wooding, S. P. Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception. Chem. Senses 38, 475–484 (2013).

    Article  CAS  PubMed  Google Scholar 

  169. Garneau, N. L. et al. Crowdsourcing taste research: genetic and phenotypic predictors of bitter taste perception as a model. Front. Integr. Neurosci. 8, 33 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  170. Risso, D. S. et al. Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal. Sci. Rep. 6, 25506 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Mennella, J. A., Pepino, M. Y., Duke, F. F. & Reed, D. R. Age modifies the genotype-phenotype relationship for the bitter receptor TAS2R38. BMC Genet. 11, 60 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Anliker, J. A., Bartoshuk, L., Ferris, A. M. & Hooks, L. D. Children’s food preferences and genetic sensitivity to the bitter taste of 6-n-propylthiouracil (PROP). Am. J. Clin. Nutr. 54, 316–320 (1991).

    Article  CAS  PubMed  Google Scholar 

  173. Guo, S. W. & Reed, D. R. The genetics of phenylthiocarbamide perception. Ann. Hum. Biol. 28, 111–142 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Chupeerach, C. et al. The influence of TAS2R38 bitter taste gene polymorphisms on obesity risk in three racially diverse groups. Biomedicine 11, 43–49 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Duffy, V. B. et al. Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake. Alcohol Clin. Exp. Res. 28, 1629–1637 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Psichas, A. et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. 39, 424–429 (2015).

    Article  CAS  Google Scholar 

  177. Tolhurst, G. et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364–371 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Lin, H. V. et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One7, e35240 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Canfora, E. E., Meex, R. C. R., Venema, K. & Blaak, E. E. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat. Rev. Endocrinol. 15, 261–273 (2019).

    Article  CAS  PubMed  Google Scholar 

  180. Derrien, M., Vaughan, E. E., Plugge, C. M. & de Vos, W. M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol. 54, 1469–1476 (2004).

    Article  CAS  PubMed  Google Scholar 

  181. Khan, A. S., Murtaza, B., Hichami, A. & Khan, N. A. A cross-talk between fat and bitter taste modalities. Biochimie 159, 3–8 (2019).

    Article  CAS  PubMed  Google Scholar 

  182. Lee, R. J. & Cohen, N. A. Taste receptors in innate immunity. Cell Mol. Life Sci. 72, 217–236 (2015).

    Article  CAS  PubMed  Google Scholar 

  183. Liu, C. L. & Shi, G. P. Calcium-activated chloride channel regulator 1 (CLCA1): more than a regulator of chloride transport and mucus production. World Allergy Organ. J. 12, 100077 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Yule, A., Sills, D., Smith, S., Spiller, R. & Smyth, A. R. Thinking outside the box: a review of gastrointestinal symptoms and complications in cystic fibrosis. Expert Rev. Respir. Med. 17, 547–561 (2023).

    Article  CAS  PubMed  Google Scholar 

  185. Di Pizio, A., Behrens, M. & Krautwurst, D. Beyond the flavour: the potential druggability of chemosensory G protein-coupled receptors. Int. J. Mol. Sci. 20, 1402 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Sternini, C. In search of a role for carbonation: is this a good or bad taste? Gastroenterology 145, 500–503 (2013).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors were in part funded by NIH DK09844 (C.S.) and P30 DK41301 (E.R.), Imaging and Stem Cell Biology Core (C.S.).

Author information

Authors and Affiliations

  1. Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Catia Sternini & Enrique Rozengurt

  2. Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Catia Sternini & Enrique Rozengurt

  3. Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Catia Sternini

  4. Molecular Biology Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Enrique Rozengurt

Authors
  1. Catia Sternini
    View author publications

    Search author on:PubMed Google Scholar

  2. Enrique Rozengurt
    View author publications

    Search author on:PubMed Google Scholar

Contributions

C.S. researched data for the article and wrote the article. Both authors contributed substantially to discussion of content and reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Catia Sternini.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Gastroenterology & Hepatology thanks Antonella Di Pizio, who co-reviewed with Malgorzata Kogut-Günthel, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sternini, C., Rozengurt, E. Bitter taste receptors as sensors of gut luminal contents. Nat Rev Gastroenterol Hepatol 22, 39–53 (2025). https://doi.org/10.1038/s41575-024-01005-z

Download citation

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41575-024-01005-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing