Luminal Chemosensory Cells in the Small Intestine

Abstract

In addition to the small intestine’s 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.

Mechanisms Underlying Food-Triggered Symptoms in Disorders of Gut-Brain Interactions

“…In terms of nutrient chemosensing, the upper small bowel expresses a large number of specialized receptors which can detect all the main categories of nutrients. The presence of glucose, fatty acids, and amino acids is monitored through large numbers of specific receptors or transporters ( 1 , 7 , 8 ). These include direct depolarisation through the sodium-glucose co-transporter-1 (SGLT1); G-protein-coupled receptors, FFAR1 (previously GPR40), FFAR3 (previously GPR41), FFAR2 (previously GPR43) and FFAR4 (previously GPR120); CD36; the calcium-sensing receptor; metabotropic glutamate receptors, GPRC6A and GPR93.…”

“…These include direct depolarisation through the sodium-glucose co-transporter-1 (SGLT1); G-protein-coupled receptors, FFAR1 (previously GPR40), FFAR3 (previously GPR41), FFAR2 (previously GPR43) and FFAR4 (previously GPR120); CD36; the calcium-sensing receptor; metabotropic glutamate receptors, GPRC6A and GPR93. Activation of these receptors leads to release of gut peptides and mediators such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), GPCR interacting protein, peptide YY (PYY), 5-hydroxytryptamine (5-HT) and the lipid signaling molecule oleoylethanolamide ( 1 , 7 , 8 ).…”

“…The mucosa also expresses taste receptors of the G-protein coupled families T1R and T2R which are sensitive to stimuli similar to taste cells on the tongue. Taste receptors and several TRP channels seem to be mainly expressed on entero-endocrine cells, where they also modulate the release of gut peptides in response to presence or absence of nutrients in the lumen ( 1 , 7 , 8 , 10 ).…”

Not Only COVID-19: Involvement of Multiple Chemosensory Systems in Human Diseases

“…The olfactory epithelium also hosts microvillous cells, which have been suggested to modulate local responses ( Hansen and Finger, 2008 ). They express the TrpM5 receptor, a calcium-activated voltage- and temperature-dependent channel for monovalent cation influx, which serves as downstream effector in bitter, sweet, and umami transduction both in taste and solitary chemoreceptor cells (see below; Burman and Kaji, 2021 ). Other receptors are present in rodents, but they are either absent or debated in humans, and these include the membrane guanylyl cyclase- D in olfactory and septal organ neurons and the seven transmembrane GPCRs vomeronasal receptors type 1 and 2 ( Fleischer et al, 2009 ), not reviewed here.…”

“…Moreover, they are sensitive to mechanical stimuli and hence regulate gastrointestinal motility ( Martin et al, 2017 ). Enterochromaffin cells are a subset of enteroendocrine cells ( Gunawardene et al, 2011 ), which sense long-chain fatty acids through CD36, GPR40, and GPR120; short-chain fatty acids through GPR41 and GPR43; endogenous lipid metabolites with GPR119; glucose through SGLT1; aminoacids through umami taste receptor, CaSR, and GPRC6A; and peptides through PepT1, leading to GLP1 and cholecystokinin release ( Raka et al, 2019 ; Burman and Kaji, 2021 ; Duca et al, 2021 ). They are innervated by the vagus nerve ( Kaelberer et al, 2018 ), depicting a neural pathway for direct nutrient sensing.…”