{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:49:07Z","timestamp":1788580147163,"version":"build-2803163510"},"reference-count":132,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK128190"],"award-info":[{"award-number":["R01DK128190"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Histochemical Society","award":["Cornerstone Award"],"award-info":[{"award-number":["Cornerstone Award"]}]},{"name":"Vanderbilt Digestive Research Center","award":["P30 058404"],"award-info":[{"award-number":["P30 058404"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>In addition to the small intestine\u2019s well-known function of nutrient absorption, the small intestine also plays a major role in nutrient sensing. Similar to taste sensors seen on the tongue, GPCR-coupled nutrient sensors are expressed throughout the intestinal epithelium and respond to nutrients found in the lumen. These taste receptors respond to specific ligands, such as digested carbohydrates, fats, and proteins. The activation of nutrient sensors in the intestine allows for the induction of signaling pathways needed for the digestive system to process an influx of nutrients. Such processes include those related to glucose homeostasis and satiety. Defects in intestinal nutrient sensing have been linked to a variety of metabolic disorders, such as type 2 diabetes and obesity. Here, we review recent updates in the mechanisms related to intestinal nutrient sensors, particularly in enteroendocrine cells, and their pathological roles in disease. Additionally, we highlight the emerging nutrient sensing role of tuft cells and recent work using enteroids as a sensory organ model.<\/jats:p>","DOI":"10.3390\/nu13113712","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T22:07:11Z","timestamp":1635113231000},"page":"3712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Luminal Chemosensory Cells in the Small Intestine"],"prefix":"10.3390","volume":"13","author":[{"given":"Andreanna","family":"Burman","sequence":"first","affiliation":[{"name":"Cell and Developmental Biology and Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-0497","authenticated-orcid":false,"given":"Izumi","family":"Kaji","sequence":"additional","affiliation":[{"name":"Epithelial Biology Center and Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1017\/S0029665120007120","article-title":"Nutrient sensing of gut luminal environment","volume":"80","author":"Moran","year":"2020","journal-title":"Proc. Nutr. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lu, V.B., Gribble, F.M., and Reimann, F. (2021). Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion. Nutrients, 13.","DOI":"10.3390\/nu13030883"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1042\/BST0330302","article-title":"Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells","volume":"33","author":"Dyer","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref_4","first-page":"41","article-title":"Taste-Signaling Proteins Are Coexpressed in Solitary Intestinal Epithelial Cells","volume":"32","author":"Damak","year":"2006","journal-title":"Chem. Senses"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"568991","DOI":"10.3389\/fnut.2020.568991","article-title":"Short Chain Fatty Acids Enhance Expression and Activity of the Umami Taste Receptor in Enteroendocrine Cells via a G\u03b1(i\/o) Pathway","volume":"7","author":"Shackley","year":"2020","journal-title":"Front Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15075","DOI":"10.1073\/pnas.0706678104","article-title":"T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1","volume":"104","author":"Margolskee","year":"2007","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1073\/pnas.072090199","article-title":"Human receptors for sweet and umami taste","volume":"99","author":"Li","year":"2002","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15069","DOI":"10.1073\/pnas.0706890104","article-title":"Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1","volume":"104","author":"Jang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1749-6632.2009.04485.x","article-title":"T1r3 and \u03b1-Gustducin in Gut Regulate Secretion of Glucagon-like Peptide-1","volume":"1170","author":"Kokrashvili","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.molmet.2018.08.009","article-title":"T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways","volume":"17","author":"Smith","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.clnu.2011.01.007","article-title":"The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)","volume":"30","author":"Steinert","year":"2011","journal-title":"Clin. Nutr."},{"key":"ref_12","first-page":"E317","article-title":"The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans","volume":"301","author":"Gerspach","year":"2011","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_13","first-page":"E1053","article-title":"Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects","volume":"310","author":"Woelnerhanssen","year":"2016","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/357563a0","article-title":"Gustducin is a taste-cell-specific G protein closely related to the transducins","volume":"357","author":"McLaughlin","year":"1992","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6631","DOI":"10.1073\/pnas.93.13.6631","article-title":"Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin","volume":"93","author":"Hofer","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"C742","DOI":"10.1152\/ajpcell.2001.280.4.C742","article-title":"Bitter taste transduced by PLC-\u03b22-dependent rise in IP3 and \u03b1-gustducin-dependent fall in cyclic nucleotides","volume":"280","author":"Yan","year":"2001","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0092-8674(03)00071-0","article-title":"Coding of Sweet, Bitter, and Umami Tastes: Different Receptor Cells Sharing Similar Signaling Pathways","volume":"112","author":"Zhang","year":"2003","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15166","DOI":"10.1073\/pnas.2334624100","article-title":"TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i","volume":"100","author":"Prawitt","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15160","DOI":"10.1073\/pnas.2334159100","article-title":"Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5","volume":"100","author":"Liu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Saltiel, M.Y., Kuhre, R.E., Christiansen, C.B., Eliasen, R., Conde-Frieboes, K.W., Rosenkilde, M.M., and Holst, J.J. (2017). Sweet Taste Receptor Ac-tivation in the Gut Is of Limited Importance for Glucose-Stimulated GLP-1 and GIP Secretion. Nutrients, 9.","DOI":"10.3390\/nu9040418"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"G439","DOI":"10.1152\/ajpgi.00079.2006","article-title":"Luminal glucose sensing in the rat intestine has characteristics of a so-dium-glucose cotransporter","volume":"291","author":"Freeman","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_22","first-page":"E1358","article-title":"Activation of sodium-glucose cotransporter 1 ameliorates hyperglycemia by mediating incretin secretion in mice","volume":"297","author":"Moriya","year":"2009","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_23","first-page":"118974","article-title":"Intestinal sodium\/glucose cotransporter 3 expression is epithelial and downregulated in obesity","volume":"267","author":"Casselbrant","year":"2020","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2337\/db11-1029","article-title":"Na+-d-glucose Cotransporter SGLT1 is Pivotal for Intestinal Glucose Absorption and Glucose-Dependent Incretin Secretion","volume":"61","author":"Gorboulev","year":"2011","journal-title":"Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"R\u00f6der, P.V., Geillinger, K.E., Zietek, T.S., Thorens, B., Koepsell, H., and Daniel, H. (2014). The Role of SGLT1 and GLUT2 in Intestinal Glucose Transport and Sensing. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089977"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1124\/jpet.112.193045","article-title":"KGA-2727, a Novel Selective Inhibitor of a High-Affinity Sodium Glucose Cotransporter (SGLT1), Exhibits Antidiabetic Efficacy in Rodent Models","volume":"342","author":"Shibazaki","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1124\/jpet.113.203364","article-title":"LX4211 Increases Serum Glucagon-Like Peptide 1 and Peptide YY Levels by Reducing Sodium\/Glucose Cotransporter 1 (SGLT1)\u2013Mediated Absorption of Intestinal Glucose","volume":"345","author":"Powell","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R1965","DOI":"10.1152\/ajpregu.1997.273.6.R1965","article-title":"Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo","volume":"273","author":"Cheeseman","year":"1997","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1042\/bj20020393","article-title":"Rapid insertion of GLUT2 into the rat jejunal brush-border membrane pro-moted by glucagon-like peptide 2","volume":"367","author":"Au","year":"2002","journal-title":"Biochem. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1113\/jphysiol.2011.223800","article-title":"The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine","volume":"590","author":"Mace","year":"2012","journal-title":"J. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mce.2007.06.003","article-title":"GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion","volume":"276","author":"Cani","year":"2007","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1113\/jphysiol.2008.159616","article-title":"An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine","volume":"587","author":"Mace","year":"2009","journal-title":"J. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1136\/gut.2008.148932","article-title":"Expression of taste molecules in the upper gastrointestinal tract in humans with and without type 2 diabetes","volume":"58","author":"Young","year":"2008","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1358\/dnp.1998.11.2.659947","article-title":"Glucagon-like peptide-1 in the pathogenesis of obesity","volume":"11","author":"Naslund","year":"1998","journal-title":"Drug News Perspect."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1159\/000497122","article-title":"Secretion of Gut Hormones and Expression of Sweet Taste Receptors and Glucose Transporters in a Rat Model of Obesity","volume":"12","author":"Feng","year":"2019","journal-title":"Obes. Facts"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1021\/acs.jafc.9b04995","article-title":"Consumption of a Natural High-Intensity Sweetener Enhances Activity and Expression of Rabbit Intestinal Na+\/Glucose Cotransporter 1 (SGLT1) and Improves Colibacillosis-Induced Enteric Disorders","volume":"68","author":"Moran","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"C1168","DOI":"10.1152\/ajpcell.1997.273.4.C1168","article-title":"Ca2+-sensing receptors in intestinal epithelium","volume":"273","author":"Gama","year":"1997","journal-title":"Am. J. Physiol. Content"},{"key":"ref_38","first-page":"G122","article-title":"Identification and localization of extracellular Ca2+-sensing receptor in rat intestine","volume":"274","author":"Chattopadhyay","year":"1998","journal-title":"Am. J. Physiol. Content"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1177\/002215540004800503","article-title":"Immunocytochemical Localization of the Extracellular Calcium-Sensing Receptor in Normal and Malignant Human Large Intestinal Mucosa","volume":"48","author":"Sheinin","year":"2000","journal-title":"J. Histochem. Cytochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1002\/oby.21083","article-title":"GPRC6a is not required for the effects of a high-protein diet on body weight in mice","volume":"23","author":"Alamshah","year":"2015","journal-title":"Obesity"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Baumard, L., Weerts, Z., Masclee, A., Keszthelyi, D., Michael-Titus, A., and Peiris, M. (2021). Effect of Obesity on the Expression of Nutrient Receptors and Satiety Hormones in the Human Colon. Nutrients, 13.","DOI":"10.3390\/nu13041271"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/sj.bjp.0702980","article-title":"Functional group I metabotropic glutamate receptors in submucous plexus of guinea-pig ileum","volume":"128","author":"Hu","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_43","first-page":"G992","article-title":"Localization and function of metabotropic glutamate receptor 8 in the enteric nervous system","volume":"285","author":"Tong","year":"2003","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1053\/j.gastro.2009.09.055","article-title":"Lysophosphatidic Acid Stimulates the Intestinal Brush Border Na+\/H+ Exchanger 3 and Fluid Absorption via LPA5 and NHERF2","volume":"138","author":"Lin","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1136\/gutjnl-2014-306834","article-title":"Mechanisms of activation of mouse and human en-teroendocrine cells by nutrients","volume":"64","author":"Symonds","year":"2015","journal-title":"Gut"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/72053","article-title":"A metabotropic glutamate receptor variant functions as a taste receptor","volume":"3","author":"Chaudhari","year":"2000","journal-title":"Nat. Neurosci."},{"key":"ref_47","first-page":"G781","article-title":"Luminal l-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats","volume":"297","author":"Akiba","year":"2009","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_48","first-page":"G98","article-title":"Identification of a protein hydrolysate responsive G protein-coupled receptor in enterocytes","volume":"292","author":"Choi","year":"2007","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_49","first-page":"G1366","article-title":"GPR93 activation by protein hydrolysate induces CCK transcription and secretion in STC-1 cells","volume":"292","author":"Choi","year":"2007","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/sj.bjp.0707121","article-title":"Pharmacological characterization of mouse GPRC6A, an L-alpha-amino-acid receptor modulated by divalent cations","volume":"150","author":"Christiansen","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Mizokami, A., Yasutake, Y., Gao, J., Matsuda, M., Takahashi, I., Takeuchi, H., and Hirata, M. (2013). Osteocalcin Induces Release of Glucagon-Like Peptide-1 and Thereby Stimulates Insulin Secretion in Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057375"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4513","DOI":"10.1074\/jbc.M112.402677","article-title":"The G Protein-coupled Receptor Family C Group 6 Subtype A (GPRC6A) Receptor Is Involved in Amino Acid-induced Glucagon-like Peptide-1 Secretion from GLUTag Cells","volume":"288","author":"Oya","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nature726","article-title":"An amino-acid taste receptor","volume":"416","author":"Nelson","year":"2002","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7674","DOI":"10.1523\/JNEUROSCI.2441-04.2004","article-title":"Umami taste responses are mediated by al-pha-transducin and alpha-gustducin","volume":"24","author":"He","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_55","first-page":"G271","article-title":"Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion","volume":"304","author":"Daly","year":"2013","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_56","first-page":"E874","article-title":"Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms","volume":"320","author":"Modvig","year":"2021","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1007\/s00125-013-3037-3","article-title":"Oligopeptides stimulate glucagon-like peptide-1 secretion in mice through proton-coupled uptake and the calcium-sensing receptor","volume":"56","author":"Diakogiannaki","year":"2013","journal-title":"Diabetologia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"G538","DOI":"10.1152\/ajpgi.00342.2010","article-title":"The extracellular calcium-sensing receptor is required for chole-cystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells","volume":"300","author":"Liou","year":"2011","journal-title":"Am. J. Gastrointest. Liver Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1038\/ijo.2017.164","article-title":"l-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents","volume":"41","author":"Alamshah","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"G753","DOI":"10.1152\/ajpgi.00189.2006","article-title":"Taste receptors in the gastrointestinal tract. II. L-amino acid sensing by calcium-sensing re-ceptors: Implications for GI physiology","volume":"291","author":"Conigrave","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1124\/mol.109.058784","article-title":"Agonists and Allosteric Modulators of the Calcium-Sensing Receptor and Their Therapeutic Applications","volume":"76","author":"Saidak","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.3945\/ajcn.115.114538","article-title":"Comparative effects of intra-duodenal whey protein hydrolysate on antropyloroduodenal motility, gut hormones, glycemia, appetite, and energy intake in lean and obese men","volume":"102","author":"Hutchison","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.metabol.2008.01.015","article-title":"Moderate protein intake improves total and regional body composition and insulin sensitivity in overweight adults","volume":"57","author":"Arciero","year":"2008","journal-title":"Metabolism"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/ajcn\/82.1.76","article-title":"Co-ingestion of a protein hy-drolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes","volume":"82","author":"Manders","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00521","DOI":"10.1002\/prp2.521","article-title":"The calcium-sensing receptor: A novel target for treatment and prophylaxis of neratinib-induced diarrhea","volume":"7","author":"Lysyy","year":"2019","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3389\/fphys.2019.00439","article-title":"Activation of the Calcium Sensing Receptor Decreases Secretagogue-Induced Fluid Secretion in the Rat Small Intestine","volume":"10","author":"Barahona","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_67","first-page":"1091","article-title":"Role of Short Chain Fatty Acid Receptors in Intestinal Physiology and Pathophysiology","volume":"8","author":"Priyadarshini","year":"2011","journal-title":"Compr. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11312","DOI":"10.1074\/jbc.M211609200","article-title":"The Orphan G Protein-coupled Receptors GPR41 and GPR43 Are Activated by Propionate and Other Short Chain Carboxylic Acids","volume":"278","author":"Brown","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nm1168","article-title":"Free fatty acids regulate gut incretin gluca-gon-like peptide-1 secretion through GPR120","volume":"11","author":"Hirasawa","year":"2005","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"11303","DOI":"10.1074\/jbc.M211495200","article-title":"The Orphan G Protein-coupled Receptor GPR40 Is Activated by Medium and Long Chain Fatty Acids","volume":"278","author":"Briscoe","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.cmet.2008.11.002","article-title":"Glucose Sensing in L Cells: A Primary Cell Study","volume":"8","author":"Reimann","year":"2008","journal-title":"Cell Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.cell.2010.07.041","article-title":"GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects","volume":"142","author":"Oh","year":"2010","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"25481","DOI":"10.1074\/jbc.M301403200","article-title":"Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation","volume":"278","author":"Loison","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1073\/pnas.2637002100","article-title":"Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41","volume":"101","author":"Xiong","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1210\/en.2008-0059","article-title":"Activation of G Protein-Coupled Receptor 43 in Adipocytes Leads to Inhibition of Lipolysis and Suppression of Plasma Free Fatty Acids","volume":"149","author":"Ge","year":"2008","journal-title":"Endocrinology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.2337\/db08-0307","article-title":"Gpr40 Is Expressed in Enteroendocrine Cells and Mediates Free Fatty Acid Stimulation of Incretin Secretion","volume":"57","author":"Edfalk","year":"2008","journal-title":"Diabetes"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1111\/jdi.13059","article-title":"Free fatty acid receptors, G protein-coupled receptor 120 and G protein-coupled receptor 40, are essential for oil-induced gastric inhibitory polypeptide secretion","volume":"10","author":"Sankoda","year":"2019","journal-title":"J. Diabetes Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cmet.2006.02.004","article-title":"Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents","volume":"3","author":"Overton","year":"2006","journal-title":"Cell Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.bbrc.2004.11.120","article-title":"Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor","volume":"326","author":"Soga","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1210\/en.2006-1608","article-title":"A Role for \u03b2-Cell-Expressed G Protein-Coupled Re-ceptor 119 in Glycemic Control by Enhancing Glucose-Dependent Insulin Release","volume":"148","author":"Chu","year":"2007","journal-title":"Endocrinology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"17665","DOI":"10.1016\/S0021-9258(17)46753-6","article-title":"Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36","volume":"268","author":"Abumrad","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Masson, C.J., Plat, J., Mensink, R.P., Namiot, A., Kisielewski, W., Namiot, Z., Fullekrug, J., Ehehalt, R., Glatz, J.F.C., and Pelsers, M.M.A.L. (2010). Fatty acid- and cholesterol transporter protein expression along the human intestinal tract. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010380"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"19493","DOI":"10.1074\/jbc.M703330200","article-title":"CD36 Is Important for Fatty Acid and Cholesterol Uptake by the Proximal but Not Distal Intestine","volume":"282","author":"Nassir","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cmet.2008.08.005","article-title":"The Lipid Messenger OEA Links Dietary Fat Intake to Satiety","volume":"8","author":"Schwartz","year":"2008","journal-title":"Cell Metab."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1096\/fj.12-217703","article-title":"CD36-dependent signaling mediates fatty ac-id-induced gut release of secretin and cholecystokinin","volume":"27","author":"Sundaresan","year":"2013","journal-title":"FASEB J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1210\/jc.2017-01982","article-title":"CD36 Modulates Fasting and Preabsorptive Hormone and Bile Acid Levels","volume":"103","author":"Shibao","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_87","first-page":"G438","article-title":"Postabsorptive factors are important for satiation in rats after a lipid meal","volume":"271","author":"Sakata","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"25201","DOI":"10.1074\/jbc.M111.233551","article-title":"Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis","volume":"286","author":"Tran","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"G958","DOI":"10.1152\/ajpgi.00134.2014","article-title":"Characterization of duodenal expression and local-ization of fatty acid-sensing receptors in humans: Relationships with body mass index","volume":"307","author":"Little","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, P., Han, G., Ganpathy, P., Pitre, S., Zhang, Y., Ryan, J., Sim, P.Y., Harding, S.V., Gray, R., and Preedy, V.R. (2020). Chronic Effects of a High Sucrose Diet on Murine Gastro-intestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010137"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"669672","DOI":"10.3389\/fimmu.2021.669672","article-title":"Trans Fatty Acid Intake Induces In-testinal Inflammation and Impaired Glucose Tolerance","volume":"12","author":"Okamura","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.lfs.2013.11.010","article-title":"Novel GPR40 agonist AS2575959 exhibits glucose metabolism improvement and synergistic effect with sitagliptin on insulin and incretin secretion","volume":"94","author":"Tanaka","year":"2014","journal-title":"Life Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1600-0463.1956.tb06739.x","article-title":"On the cellular structures of the epithelial invasions in the glandular stomach of mice caused by intramural application of 20-methylcholantren","volume":"39","author":"Jarvi","year":"1956","journal-title":"Acta Pathol. Microbiol. Scand. Suppl."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/BF00345847","article-title":"Electron microscopy of the tracheal ciliated mucosa in rat","volume":"44","author":"Rhodin","year":"1956","journal-title":"Z. Zellforsch. Mikrosk. Anat."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1083\/jcb.201010127","article-title":"Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium","volume":"192","author":"Gerbe","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8877","DOI":"10.1038\/s41598-020-65469-0","article-title":"Mouse intestinal tuft cells express advillin but not villin","volume":"10","author":"Esmaeilniakooshkghazi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e150416","DOI":"10.1172\/jci.insight.150416","article-title":"Cell differentiation is disrupted by MYO5B loss through Wnt\/Notch imbalance","volume":"6","author":"Kaji","year":"2021","journal-title":"JCI Insight"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nn.2820","article-title":"Skn-1a (Pou2f3) specifies taste receptor cell lineage","volume":"14","author":"Matsumoto","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nature16527","article-title":"Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites","volume":"529","author":"Gerbe","year":"2016","journal-title":"Nature"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature24489","article-title":"A single-cell survey of the small intestinal epithelium","volume":"551","author":"Haber","year":"2017","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"587664","DOI":"10.3389\/fphar.2020.587664","article-title":"G Protein-Coupled Receptors in Taste Physiology and Pharmacology","volume":"11","author":"Ahmad","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"17466","DOI":"10.1038\/s41598-019-53997-3","article-title":"Distribution pattern and molecular signature of cholinergic tuft cells in human gastro-intestinal and pancreatic-biliary tract","volume":"9","author":"Ruppert","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e93487","DOI":"10.1172\/jci.insight.93487","article-title":"Optimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneity","volume":"2","author":"McKinley","year":"2017","journal-title":"JCI Insight"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1369\/0022155417702586","article-title":"Tyrosine Phosphorylation of an Actin-Binding Protein Girdin Specifically Marks Tuft Cells in Human and Mouse Gut","volume":"65","author":"Kuga","year":"2017","journal-title":"J. Histochem. Cytochem."},{"key":"ref_105","first-page":"87","article-title":"Chemical coding and chemosensory prop-erties of cholinergic brush cells in the mouse gastrointestinal and biliary tract","volume":"6","author":"Jurastow","year":"2015","journal-title":"Front Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Zappia, K.J., O\u2019Hara, C.L., Moehring, F., Kwan, K.Y., and Stucky, C.L. (2017). Sensory Neuron-Specific Deletion of TRPA1 Results in Me-chanical Cutaneous Sensory Deficits. eNeuro, 4.","DOI":"10.1523\/ENEURO.0069-16.2017"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/stem.1566","article-title":"Brief Report: Dclk1 Deletion in Tuft Cells Results in Impaired Epithelial Repair After Radiation Injury","volume":"32","author":"May","year":"2013","journal-title":"Stem Cells"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1172\/JCI73434","article-title":"Long-lived intestinal tuft cells serve as colon cancer\u2013initiating cells","volume":"124","author":"Westphalen","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2220\/biomedres.41.113","article-title":"Distribution of duodenal tuft cells is altered in pediatric patients with acute and chronic enteropathy","volume":"41","author":"Huh","year":"2020","journal-title":"Biomed. Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"McSorley, H.J., Gaze, S., Daveson, J., Jones, D., Anderson, R.P., Clouston, A., Ruyssers, N.E., Speare, R., McCarthy, J.S., and Engwerda, C.R. (2011). Suppression of Inflammatory Immune Responses in Celiac Disease by Experimental Hookworm Infection. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024092"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/pim.12175","article-title":"Clinical trials of helminth therapy in autoimmune diseases: Rationale and findings","volume":"37","author":"Fleming","year":"2015","journal-title":"Parasite Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Ryan, S.M., Eichenberger, R.M., Ruscher, R., Giacomin, P.R., and Loukas, A. (2020). Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008508"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature16161","article-title":"Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit","volume":"529","author":"Ji","year":"2016","journal-title":"Nature"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev-immunol-042718-041505","article-title":"Tuft Cells\u2014Systemically Dispersed Sensory Epithelia Integrating Immune and Neural Circuitry","volume":"37","author":"Schneider","year":"2019","journal-title":"Annu. Rev. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.coi.2020.09.006","article-title":"Tuning tuft cells: New ligands and effector functions reveal tissue-specific function","volume":"68","author":"Billipp","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1172\/JCI120330","article-title":"Interpreting heterogeneity in intestinal tuft cell structure and function","volume":"128","author":"Banerjee","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.immuni.2018.06.016","article-title":"Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit","volume":"49","author":"Nadjsombati","year":"2018","journal-title":"Immunity"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2018.05.014","article-title":"A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling","volume":"174","author":"Schneider","year":"2018","journal-title":"Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5552","DOI":"10.1073\/pnas.1720758115","article-title":"Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine","volume":"115","author":"Lei","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4049\/immunohorizons.1900099","article-title":"The Taste Receptor TAS1R3 Regulates Small Intes-tinal Tuft Cell Homeostasis","volume":"4","author":"Howitt","year":"2020","journal-title":"ImmunoHorizons"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41586-021-03852-1","article-title":"Cells of the human intestinal tract mapped across space and time","volume":"597","author":"Elmentaite","year":"2021","journal-title":"Nature"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1074\/jbc.R114.635995","article-title":"Human Enteroids\/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology","volume":"291","author":"Zachos","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1053\/j.gastro.2011.07.050","article-title":"Long-term Expansion of Epithelial Organoids From Human Colon, Adenoma, Adenocarcinoma, and Barrett\u2019s Epithelium","volume":"141","author":"Sato","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.jcmgh.2018.02.002","article-title":"Molecular Basis and Differentiation-Associated Al-terations of Anion Secretion in Human Duodenal Enteroid Monolayers","volume":"5","author":"Yin","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"45270","DOI":"10.1038\/srep45270","article-title":"A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions","volume":"7","author":"Noel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nmeth.2737","article-title":"Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny","volume":"11","author":"Yin","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1242\/dev.070763","article-title":"Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells","volume":"139","author":"VanDussen","year":"2012","journal-title":"Development"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep17185","article-title":"Characterization of stem\/progenitor cell cycle using murine circumvallate papilla taste bud organoid","volume":"5","author":"Aihara","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1038\/s41598-017-04099-5","article-title":"Transcriptome analyses of taste organoids reveal multiple pathways involved in taste cell generation","volume":"7","author":"Ren","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"101129","DOI":"10.1016\/j.molmet.2020.101129","article-title":"Intestinal stem cell-derived enteroids from morbidly obese patients preserve obesity-related phenotypes: Elevated glucose absorption and gluconeogenesis","volume":"44","author":"Hasan","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s10620-017-4867-5","article-title":"Apical Membrane Alterations in Non-intestinal Organs in Microvillus Inclusion Disease","volume":"63","author":"Schlegel","year":"2017","journal-title":"Dig. Dis. Sci."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3712\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:20:53Z","timestamp":1760167253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":132,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nu13113712"],"URL":"https:\/\/doi.org\/10.3390\/nu13113712","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]}}}