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Gut Online First, published on October 16, 2013 as 10.1136/gutjnl-2013-305112
Correspondence to
Professor Inge Depoortere, Gut
Peptide Research Lab,
Translational Research Center
for Gastrointestinal Disorders,
University of Leuven,
Gasthuisberg O&N1, box 701,
Leuven 3000, Belgium; inge.
depoortere@med.kuleuven.be
Received 29 July 2013
Revised 16 September 2013
Accepted 25 September 2013
To cite: Depoortere I. Gut
Published Online First:
[please include Day Month
Year] doi:10.1136/gutjnl-
2013-305112
Copyright
Depoortere I.Article author
Gut 2013;0:1–12.
doi:10.1136/gutjnl-2013-305112
Recent advances in basic science
Taste receptors of the gut: emerging roles in health
and disease
Inge Depoortere
ABSTRACT
Recent progress in unravelling the nutrient-sensing
mechanisms in the taste buds of the tongue has triggered
studies on the existence and role of chemosensory cells in
the gut. Indeed, the gastrointestinal tract is the key
interface between food and the human body and can
sense basic tastes in much the same way as the tongue,
through the use of similar G-protein-coupled taste
receptors. These receptors ‘taste’ the luminal content and
transmit signals that regulate nutrient transporter
expression and nutrient uptake, and also the release of
gut hormones and neurotransmitters involved in the
regulation of energy and glucose homeostasis. Hence,
they play a prominent role in the communication between
the lumen, epithelium, smooth muscle cells, afferent
nerve fibres and the brain to trigger adaptive responses
that affect gastrointestinal function, food intake and
glucose metabolism. This review summarises how sensing
of nutrients by taste receptors along the gut plays a key
role in the process of digestion, and how disturbances or
adaptations of these chemosensory signalling pathways
may contribute to the induction or resolution of a number
of pathological conditions related to diabetes, obesity, or
diet-induced symptom generation in irritable bowel
syndrome. Targeting these receptors may represent a
promising novel route for the treatment of a number of
these diseases.
INTRODUCTION
We choose to eat for many reasons, including to
satisfy our hunger, to invite pleasant sensory
experiences, and as a social ritual. However, we
need to eat to acquire nutrients essential for life
and health. Not surprisingly, the digestive system
contains a diverse array of detectors that help to
regulate ingestive decisions, impact nutrient assimi-
lation, avoid or neutralise toxins, and elicit
complex neural and endocrine responses that affect
metabolism, gastrointestinal (GI) transit, satiation
and satiety. Strikingly, many of the G protein-
coupled receptors (GPCRs) that detect nutrients
and toxins in the oral cavity and function as taste
receptors there, also subserve important functions
throughout the GI tract. Activation of these recep-
tors triggers the release of neurotransmitters (eg,
ATP) that will excite primary sensory afferent fibres
and interact with neighbouring presynaptic cells to
relay information to the hindbrain.1 A similar
system of highly orchestrated interactions also oper-
ates in the gut and further points to the functional
similarity of lingual and intestinal cells. I will
review the state of our knowledge about taste
receptor function along the entirety of the alimen-
tary canal and discuss the implications of these
functions for human physiology and disease.
(or their employer) 2013. Produced by BMJ Publishing Group Ltd (& BSG) under licence.
Key messages
▸ The gut tastes what we eat—bitter, sweet,
umami, fat—in much the same way as the
tongue through the use of similar taste
receptors and chemosensory signalling
pathways
▸ In health, taste receptors sense nutrients from
either a luminal or blood-borne direction and
transmit signals that control the secretion of
gut hormones and the expression of nutrient
transporters to maintain energy and glucose
homeostasis and gastrointestinal function
▸ In disease, disturbances or adaptations in the
expression or sensitivity of these taste receptors
and their signalling pathways may affect
digestive behaviour and metabolism
▸ This is a new and emerging field, future studies
aimed at a better understanding of how the
sensing of nutrients in the gut is finely tuned
by different taste receptors in health and
disease, should help us to define novel drug
targets
TASTE RECEPTORS AND GUSTATORY
FUNCTION
The taste system detects compounds that elicit at
least five perceptual qualities: sweet, umami, bitter,
sour and salty. The latter two are largely mediated
by ion channels, and will not be discussed further
here. By contrast, sweet, umami and bitter-tasting
stimuli are detected by members of two GPCR fam-
ilies, the taste 1 receptor family (TAS1R) and the
taste 2 receptor family (TAS2R), that are expressed
in subpopulations of taste bud cells (figure 1).
Subtypes of the TAS1R family heterodimerise to
detect sweet (TAS1R2-TAS13) and umami
(TAS1R1-TAS1R3).2 3 Animals that lack these subu-
nits are deficient in their ability to taste umami and/
or sweet stimuli.4 The presence of multiple binding
sites on these receptors can explain the synergistic
effects of 50 -ribonucleotides and glutamate in
umami taste, or the ability of many chemically
diverse compounds–including sugars, non-caloric
sweeteners, D-amino acids and some proteins–to
elicit a sweet taste. Consistent with their proposed
evolutionary need to detect foods rich in nutrients,
the umami and sweet receptors are low-affinity
receptors, with EC50s in the millimolar range for
their most common natural ligands.
Alternatively, we are quite sensitive to bitter-
tasting compounds. While this is important for
1
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Recent advances in basic science

Figure 1 Simplified model of the taste GPCR signalling pathways involved in chemosensing by taste cells of the tongue. Subtypes of the TAS1R
family heterodimerize to detect sweet (TAS1R2-TAS13) and umami (TAS1R1-TAS1R3) while bitter is detected by 25 subtypes of the TAS2R family.
Medium-chain and long-chain fatty acids are detected by FFAR1 and GPR120. Taste receptor binding leads to activation of gustatory G-proteins,
release of intracellular Ca2+, activation of TRPM5, depolarisation, activation of voltage-gated Na+ channels (VGNC) and release of ATP which
activates purinergic receptors on afferent nerve fibres leading to taste perception. ATP, adenosine triphosphate; FFAR1, free fatty acid receptor 1;
GPCR, G-protein coupled receptor; GPR120, G-protein coupled receptor 120; PX-1, pannexin 1-hemichannel; TAS1R, taste receptor type 1; TAS1R1,
taste receptor type 1 member 1; TAS1R2, taste receptor type 1 member 2; TAS1R3, taste receptor type 1 member 3; TAS2R, taste receptor type 2;
TRPM5, transient receptor potential cation channel M5; VGNC, voltage-gated Na+ channel.

avoiding potential toxins, it also reduces the oral tolerance for

many common pharmaceuticals.5 Bitter tastants are recognised Table 1 Overview of the different taste receptors involved in
by TAS2Rs.6 The human genome encodes 25 different TAS2Rs, nutrient sensing
which fall into three functional categories: specialists that
Sweet taste receptors/transporters
respond to one or two compounds; generalists that are highly
TAS1R2-TAS1R3 Taste receptor, type 1, member 2-taste
promiscuous in their stimulus responses; and those that are receptor, type 1, member 3
intermediate in their selectivity.7 Many compounds can activate SGLT1 Sodium-dependent glucose transporter 1
more than one receptor, and activation thresholds can vary GLUT Glucose transporter
from millimolar to nanomolar levels. TAS2R polymorphisms are Amino acid/peptide taste receptors
quite common in human populations, and can have pronounced TAS1R1-TAS1R3 (umami, Taste receptor, type 1, member 1-taste
effects on the ability of individuals to detect certain bitter aliphatic amino acids) receptor, type 1, member 3
compounds.8 CaSR (aromatic amino acids) Calcium sensing receptor
Other GPCRs have been implicated in the detection of gusta- GPRC6A (basic and small G-protein coupled receptor family C group 6
tory stimuli. For example, metabotropic glutamate receptors, neutral amino acids) member A
specifically mGluR1 and mGluR4, may contribute to amino mGluR (umami) Metabotropic glutamate receptor
acid taste.9 The Ca2+-sensing receptor (CaSR) and GPRC6A GPR92 (protein hydrolysates) G-protein coupled receptor 92
have been proposed to mediate Ca2+ taste and also amino acid Bitter taste receptors
taste in extraoral tissues such as the gut.10 11 Two receptors for TAS2R Taste receptor type 2
long-chain fatty acids (LCFAs), FFAR1 (a.k.a., GPR40) and Free fatty acid receptors
GPR120 have been localised to taste cells and contribute to oro- Long-chain/medium-chain fatty acids
sensory responses to fats (whether or not fat can be considered GPR120 G-protein coupled receptor 120
as the sixth taste is the subject of ongoing investigation).12 FFAR1 (also known as GPR40) Free fatty acid receptor 1
Additionally, receptors for short-chain fatty acids (SCFA), Short-chain fatty acids
FFAR2 and FFAR3, have been detected outside the oral cavity.11 FFAR2 (also known as GPR43) Free fatty acid receptor 2
An as yet unidentified receptor may mediate the taste of polysac- FFAR3 (also known as GPR41) Free fatty acid receptor 3
charides. An overview of the different taste receptors involved CaSR, calcium sensing receptor; FFAR1, free fatty acid receptor 1; FFAR2, free fatty
in nutrient sensing is represented in table 1. acid receptor 2, FFAR3, free fatty acid receptor 3; GLUT, glucose transporter; GPR92,
G-protein coupled receptor 92; GPR120, G-protein coupled receptor 92; GPRC6A,
TAS1Rs and TAS2Rs are found in Type II taste cells, a mor- G-protein coupled receptor family C group 6; mGluR, metabotropic glutamate
phological class of microvillar taste bud cells. Activation of a receptor; SGLT1, sodium-dependent glucose transporter 1; TAS1R1, taste receptor
gustatory G-protein (eg, gustducin) coupled to these GPCRs type 1 member 1; TAS1R2, taste receptor type 1 member 2; TAS1R3, taste receptor
type 1 member 3; TAS2R, taste receptor type 2.
results in the activation of phospholipase C β2 leading to

2 Depoortere I. Gut 2013;0:1–12. doi:10.1136/gutjnl-2013-305112

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Recent advances in basic science

inositoltriphosphate-mediated release of intracellular Ca2+ and
activation of the transient receptor potential cation channel M5
(TRPM5) (figure 1). These events induce membrane depolarisa-
tion, action potential generation, and the release of ATP, which
acts on purinergic receptors to activate gustatory afferents
leading to activation of brain centres involved in taste percep-
tion. Sweet, umami and bitter taste receptors are differentially
expressed within the Type II taste cells.13 This segregation is a
key component of taste quality coding and hedonic discrimin-
ation in the gustatory periphery. The extent to which these
various taste transduction components are colocalised in gut
cells is unclear, but surely has consequences for how they
impact GI function.
ROLE OF TASTE RECEPTORS IN NUTRIENT DETECTION AND
RESPONSE DURING DIGESTION
‘Gut’ peptides produced in taste cells of the tongue
Taste cells also express a number of bioactive peptides best
known for their roles in metabolism, feeding and satiety, includ-
ing: glucagon-like peptide-1 (GLP-1), glucagon, neuropeptide Y,
peptide YY (PYY), cholecystokinin (CCK), vasoactive intestinal
peptide and ghrelin.14 The functions of these peptides in taste
buds are not fully understood, but at least some may act to
modulate the responsiveness of the peripheral gustatory appar-
atus to certain taste stimuli. Interestingly, stimuli representing
different taste qualities promote the release of different peptide
combinations, suggesting that these peptides could also play a
role in quality coding.15
Cognate receptors for all the peptides expressed in taste cells
can be found on taste cells or on the adjacent afferent nerve
fibres.14 Therefore, these peptides almost certainly have auto-
crine and paracrine functions within the taste bud and, in some
cases, could function as cotransmitters with ATP. However, it is
unclear whether taste bud peptides also reach the bloodstream
and exert endocrine effects. Furthermore, peptide receptors
expressed on taste cells may be targets of circulating peptides
produced in the gut, adipose tissue, or other tissues. For
example, systemic leptin has been shown to decrease sweet taste
responsiveness through actions on leptin receptors present on a
subset of taste cells.16 Thus, postingestive nutrient responses
could feed back onto the peripheral gustatory apparatus to
modulate its responsiveness to subsequent foods.
Nutrient sensing in the stomach
Proximal stomach
Upon ingestion of food, the proximal stomach relaxes to accom-
modate large amounts of food without increasing intragastric
pressure. Tension-sensitive mechanoreceptors are activated by
the arrival of food and relay their information via the vagus to
the hindbrain to induce sensations of satiation.17 Nutrient
sensing in the stomach has been considered to be a less import-
ant factor, but the role of chemosensory receptors should not be
ignored. Indeed, recent studies showed that intragastric adminis-
tration of the bitter agonist, denatonium benzoate (DB), inhib-
ited gastric accommodation to nutrient drink infusion and
tended to increase satiation scores.18 The contractile response
induced by DB was mimicked in vitro in smooth muscle strips
from the mouse fundus and was partially mediated via the gusta-
tory G-protein subunit, α-gustducin, and involved the release of
Ca2+ from intracellular and extracellular stores.19
The proximal stomach is also the major site of production of
the orexigenic hormone, ghrelin, which is considered as a physio-
logical meal initiator.20 How the reduction of plasma ghrelin
during a meal might participate in the induction of satiation is
incompletely explored. The fact that ghrelin levels are suppressed
strongly by ingested proteins, weakly by proteins and biphasically
by carbohydrates, suggests that the ghrelin P/D1 cells contain the
machinery to sense nutrients.21 Recent immunofluorescence
studies confirmed that the ghrelin cell is colocalised with the gus-
tatory G-proteins, α-gustducin and α-transducin, the sweet and

Figure 2 Schematic overview of the expression of taste receptors in different type of endocrine cells along the gut that control the release of
hormones in response to nutrients. CaSR, calcium sensing receptor; FFAR1, free fatty acid receptor 1; FFAR2, free fatty acid receptor 2; FFAR3, fatty
acid receptor 3; GPR92, G-protein coupled receptor 92; GPRC6A, G-protein coupled receptor family C group 6 member A; LCFA, long-chain fatty
acids; TAS1R1, taste receptor type 1 member 1; TAS1R2, taste receptor type 1 member 2; TAS1R3, taste receptor type 1 member 3; TAS2R, taste
receptor type 2.

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Recent advances in basic science
umami receptor subunit, TAS1R3, and the free fatty acid-sensing
receptor, GPR120.22–24 It remains to be investigated whether the
postprandial suppression of ghrelin by nutrients is indeed
mediated via these receptors. However, the first functional
studies showed that α-gustducin is involved in the effect of bitter
compounds on ghrelin release and in sensing of medium-chain
fatty acids in the diet necessary for the octanoylation of
ghrelin.22 23 Additionally, GPR120 seems to play a role in the
lipid-sensing cascade of the ghrelin cell.23 The distribution of
taste receptors involved in nutrient sensing in endocrine cells
along the gut is summarised in figure 2.
Distal stomach
The arrival of food in the stomach stimulates the gastric phase
of acid, pepsinogen and mucus production. The two principal
triggers are distension of the stomach, which initiates local
myenteric and vago-vagal reflexes, and the chemical content of
the food. In the stomach, sensing of protein breakdown pro-
ducts is important as they activate the release of two important
regulators of pepsinogen and acid secretion: gastrin (G-cells)
and somatostatin (D-cells). Indeed, peptone has been shown to
affect gastrin and somatostatin secretion in rats.25 Recent studies
showed that mouse and pig antral G-cells and a subpopulation
of D-cells express GPR92, a receptor activated by dietary
protein hydrolysates.26 In both endocrine cell types, GPR92 is
coupled to different signalling pathways. It is therefore conceiv-
able that GPR92 may play an important role in adjusting the
release of gastrin and somatostatin in response to protein digests
in the chyme. In addition, G and D-cells express the amino acid
taste receptor GPRC6A and the CaSR that act in concert with
each other to sense a broad spectrum of amino acids ranging
from basic and small neutral (GPRC6A) to aromatic (L-Phe)
amino acids and Ca2+.27 28 The stimulation of gastrin after
gavage with L-Phe, peptone, Ca2+ and a neutralising buffer was
abolished in CaSR−/− mice suggesting a regulatory role for this
receptor in gastrin release.29 The TAS1R family is not important
for G-cell sensing of protein and amino acids since TAS1R3 is
not expressed on G-cells and the gastrin response to peptone is
not abolished in TAS1R1/3−/− mice.28 29 Additionally, L-Phe can
induce acid secretion independent of hormonal stimulation via
activation of the CaSR on parietal cells.30
In the distal stomach, the chyme is mixed with the digestive
secretions and ground by powerful peristaltic contractions. The
process of emptying starts and the rate is dependent on the
gastric volume and the chemical nature of the gastric contents.
The major control mechanism for gastric emptying involves
duodenal gastric feedback and the emphasis shifts towards
satiety mechanisms.
When the meal is emptied from the stomach, the upper GI
motility pattern changes from a digestive to an interdigestive
pattern: the migrating motor complex, characterised by a group
of strong phasic contractions migrating distally. Phase 3 contrac-
tions, the most vigorous contractions of the migrating motor
complex (MMC), originating in the stomach, are considered as
a hunger signal. Arrival of nutrients will disrupt this pattern.
Infusion of high doses of amino acids in healthy volunteers
shortens the duration of the MMC length and suppresses antral
phase 3 activity.31 Intragastric administration of the bitter com-
pound, DB, in the fasted state was shown to decrease antral but
not duodenal motility and to shift the origin of phase 3 from
the antrum to the duodenum. This was accompanied by a sig-
nificant decrease in hunger scores.32 In both cases, the mechan-
isms involved are unknown but may involve activation of taste
receptors on endocrine cells, smooth muscle cells and/or nerves.
4 Depoortere I. Gut 2013;0:1–12. doi:10.1136/gutjnl-2013-305112
Whether any stimulus that suppresses or induces gastric phase 3
activity inhibits or stimulates hunger, respectively, requires
further investigation. Furthermore, recent studies showed that
gastric phase 3 activity was less frequently observed in obese
patients, and was associated with fewer hunger peaks suggesting
that the absence of generation of gastric MMCs may be
pro-anorexigenic and may also represent a compensatory mech-
anism to reduce hunger feelings in obesity.33 The motilin
agonist, erythromycin, known to induce gastric phase 3,
restored the association between gastric phase 3 and hunger
peaks in obese patients.
Nutrient sensing in the small intestine
The small intestine is the major site of digestion and absorption
in the GI tract. In the small intestine, carbohydrates, fats and
protein digestion products, as well as osmolarity changes and
physical distention activate inhibitory neural and endocrine
pathways that signal the stomach to delay emptying and to help
limit ingestion by enhancing gastric mechanoreceptor stimula-
tion. However, experiments demonstrated that intestinal nutri-
ent infusions inhibit food intake during sham feeding when
gastric contents were drained via an open gastric cannula to
obviate the gastric filling effects on food intake.34 Thus, while
intestinal signals and gastric emptying interact to control food
intake, a delay of gastric emptying is not required for intestinal
signals to elicit satiation. The small intestine also sends endo-
crine satiety signals to the hypothalamus, either directly, via the
bloodstream and across the incomplete blood-brain barrier to
the arcuate nucleus, or indirectly, through the activation of the
vagus nerve. It is clear that the vagal-brainstem-hypothalamic
pathway plays a major role in the effect of the satiation hor-
mones, CCK and GLP-1, on food intake. Their receptors are
expressed on vagal afferents, they increase vagal afferent firing
and induce cfos expression in the nucleus of the solitary tract
after intraperitoneal injection.35–39 Furthermore the inhibition
of food intake by exogenous GLP-1 and CCK is blocked by
vagotomy and brainstem-hypothalamic pathway
transectioning.40 41
Duodenum
In the duodenum, fat, protein hydrolysates and amino acids
stimulate the secretion of CCK from I-cells. This hormone then
acts to slow gastric emptying and increase satiety. In STC-1
cells, a mouse enteroendocrine-like cell line, LCFAs induce
CCK secretion through the lipid sensor GPR120 and the trans-
duction channel TRPM5.42 43 However, cell lines are incom-
pletely validated as accurate models of native I-cells.
Establishing cultures from endocrine cells remained a challenge
for many years but the generation of transgenic mice with I cell-
specific expression of a fluorescent protein, allowed the isolation
of a pure I-cell population by fluorescence-activated cell sorting.
Native I-cells are also immunoreactive for FFAR1, and the effect
of linolenic acid on the secretion of CCK from isolated I-cells
was abolished in cells from FFAR1−/− mice.44 45 Thus, GPR120
and FFAR1 appear to mediate lipid-induced CCK secretion.
Amino acids and protein hydrolysates similarly appear to use
multiple receptor types to stimulate CCK secretion. In humans,
administration of L-Phe increased CCK secretion and reduced
food intake.46 Two amino acid-responsive receptors,
TAS1R1-TAS1R3 and the CaSR, are expressed in I-cells, and
implicated in CCK release.47 For example, Phe-dependent,
Leu-dependent and Glu-dependent CCK release is dependent
on TAS1R1-TAS1R3, while the CaSR mediates Phe-induced and
Trp-induced responses in mouse intestinal tissue explants.47
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Studies in vitro (STC-1 cells) and in native I-cells also showed
an important role for the CaSR in the effects of aromatic amino
acids on CCK secretion.48–50 Protein hydrolysates stimulate the
release of CCK via GPR92 in STC-cells.51
Bitter tastants can also induce CCK release from STC-1 cells
by affecting Ca2+ influx.52 53
Glucose-induced CCK secretion in humans, although perhaps
not a major phenomenon, was unaffected by the sweet taste
receptor inhibitor lactisole.54 Immunolocalisation studies con-
firmed that the sweet taste receptor-specific subunit, TAS1R2, is
not coexpressed with CCK.47
Jejunum-ileum
GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)
are incretin hormones that augment insulin secretion after inges-
tion of a meal. They are secreted from L-cells and K-cells,
respectively. The mechanisms by which L-cells couple glucose
detection to GLP-1 secretion have been controversial, but some
clarity has begun to emerge (figure 3). Several lines of evidence
support that the sweet taste receptor, TAS1R2-TAS1R3, and the
taste G-protein, α-gustducin, are required for glucose-stimulated
GLP-1 secretion from the small intestine. First, these three pro-
teins are present in human and rodent L-cells of the small intes-
tine.55–57 Second, several sweet taste receptor agonists —
sucrose, glucose, fructose and sucralose — can elicit GLP-1
Figure 3 Mechanisms involved in glucose-stimulated GLP-1 release.
Glucose can stimulate gut peptide secretion by (1) binding to the sweet
taste receptor heterodimer, TAS1R2-TAS1R3, coupling via the G-protein,
gustducin, to increase intracellular Ca2+ resulting in vesicle fusion and
consequent release of GLP-1; (2) Na+-coupled glucose transport via
SGLT1 which will depolarise the membrane resulting in the opening of
voltage-gated Ca2+ channels and influx of Ca2+. Additionally, transport
of glucose into the cell via SGLT1 will lead to increased metabolism
and closure of K ATP-sensitive channels. ATP, adenosine triphosphate;
GLP-1, glucagon-like peptide; KATP, ATP-sensitive potassium channel;
PLCβ2, phospholipase C β2; TAS1R2, taste receptor type 1 member 2;
TAS1R3, taste receptor type 1 member 3; SGLT1, sodium-dependent
glucose transporter 1.
Depoortere I. Gut 2013;0:1–12. doi:10.1136/gutjnl-2013-305112
Recent advances in basic science
secretion from mouse jejunal and ileal explants, and/or mouse
(GLUTag) and human (NCI-H716) enteroendocrine cell
lines.56 58 59 Third, glucose-stimulated GLP-1 secretion is nearly
or fully abolished in α-gustducin−/− and TAS1R2−/− and
TAS1R3−/− mice.56 58 Fourth, sweet taste receptor inhibitors, or
RNA silencing of α-gustducin, reduce sucralose-stimulated
GLP-1 secretion from GLUTag and NCI-H716 cells.56 59
Finally, the sweet taste receptor inhibitor, lactisole, reduced sys-
temic levels of GLP-1 and PYY after intragastric or intraduode-
nal administration of glucose in humans.54 55
Several studies also indicated an important role for the
Na+-glucose cotransporter SGLT1 and the ATP-sensitive K+
(KATP) channel. For example, the KATP channel blocker tolbuta-
mide enhances GLP-1 secretion from GLUTag cells or from iso-
lated L-cells from upper small intestine or colon.60 61
Furthermore, immunoreactivity for one KATP channel subunit,
Kir6.2, has been localised to L-cells.62 By contrast, a related
KATP channel blocker, glibenclamide, had no effect on GLP-1
secretion from mouse ileum explants, but did induce GLP-1
secretion from colonic explants, suggesting that this channel is
involved in GLP-1 secretion from L-cells of the large, but not
small intestine.58 The evidence for a role of SGLT1 is more
intriguing, as SGLT1−/− mice exhibit reduced GLP-1 and GIP
levels after glucose gavage.63 A role for SGLT1 in
glucose-induced GLP-1 release has been confirmed in GLUTag
cells and primary L-cells.61 64 65
A physiological relationship exists between L-cells and entero-
cytes. SGLT1 and another glucose transporter, GLUT2, are
rapidly upregulated in enterocytes in response to the presence
of dietary sugars or sweeteners. However, their expression and/
or translocation is downregulated in TAS1R3−/− and
α-gustducin−/− mice, suggesting a strong correlation between
taste receptor activation in L-cells and the modulation of
glucose transporter expression in enterocytes, likely through the
actions of GLP-2.59 66 67 Cats which cannot taste sugars do not
upregulate SGLT1 expression in response to increased dietary
carbohydrate levels.68 69
It is unclear whether FFAR1 or GPR120 play the more
important role in L-cell and K-cell fatty acid sensing. Both
receptors are expressed in L-cells.44 70 Oral administration of
α-linolenic acid promoted GLP-1 secretion in vivo.70 In STC-1
cells, however, siRNA against GPR120, but not FFAR1,
impaired α-linolenic acid-induced GLP-1 secretion.
Nevertheless, the secretion of GIP and GLP-1 in response to
acute, oral fat diet administration was reduced in FFAR1−/−
mice and was associated with a concomitant reduction in insulin
secretion and glucose clearance.44
Bitter ligands stimulate GLP-1 secretion from TAS2R-expressing
enteroendocrine cell lines (STC-1 and NCI-H716), suggesting that
bitter taste receptors could have an impact on glucose and insulin
regulation.52 71 In fact, in an Amish Family Diabetes Study, a func-
tionally comprised TAS2R was associated with disturbed glucose
homeostasis.71
GPRC6A was recently shown to act as an amino acid sensor
in GLUTag that enhances GLP-1 secretion.72
Nutrient sensing in the colon
The main function of the colon is to store food residues, secrete
mucus and absorb remaining water and electrolytes from the
food residue before defecation. The colon exhibits segmental
movements (haustrations) and phasic propulsive contractions.
The intestinal flora performs fermentation reactions that
produce SCFA and flatus.
5
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SCFAs ( propionate, acetate and butyrate) are sensed in the
lumen by the free fatty acid receptors, FFAR2 and FFAR3.73 In
the human colon, FFAR2 immunoreactive cells were colocalised
with PYY-containing L-cells but not with 5-HT containing endo-
crine cells.74 In the rat colon, 5-HT-containing mucosal mast
cells were immunoreactive for FFAR2.75 FFAR3-positive cells in
the human colon were less abundantly present than FFAR2 cells
and contained PYY but not 5-HT or FFAR2.76 α-gustducin Is
colocalised with several fatty acid receptors present on endo-
crine cells in the mouse colon and is required for
SCFA-mediated GLP-1 release from mucosal explants.77 The
effect of SCFA on the release of GLP-1 was also confirmed in
isolated primary L-cells from mouse colon. In FFAR2−/− and
FFAR3−/− mice reduced SCFA-induced GLP-1 secretion was
observed in vitro and in vivo together with a parallel impair-
ment of glucose tolerance.78
The functional role of TAS1R3 in L-cells of the human colon
is not clear.55 GLP-1-secreting cells of the colon and rectum are
normally not responsive to sugars, suggesting no role for the
sweet taste receptor in hindgut GLP-1 secretion. Even when
these cells become glucose-responsive in association with carbo-
hydrate malabsorption, for instance after gastric bypass surgery,
this glucose sensitivity is sweet taste receptor independent (the
identity of the glucose sensor is unknown).
CONTRIBUTIONS OF TASTE RECEPTORS TO
PATHOPHYSIOLOGY: POSSIBLE TARGETS FOR THERAPY?
Glucose homeostasis and diabetes
Young et al79 80 were the first to compare the intestinal levels of
sweet taste receptors in patients with well-controlled type 2 dia-
betes to those without diabetes. Absolute levels of TAS1R2,
TAS1R3, α-gustducin or TRPM5 transcripts in the duodenum
of healthy people, or patients with type 2 diabetes, were
unaffected by acute variations in glycaemia during fasting.
However, the intestinal sweet taste receptor system was highly
responsive to changes in luminal glucose. During euglycemia,
intraduodenal glucose infusion increased TAS1R2 transcript
levels in both groups but during hyperglycaemia TAS1R2
mRNA expression decreased in healthy volunteers but not in
diabetics. Levels of TAS1R3 did not change significantly. The
TAS1R2 dysregulation in patients with type 2 diabetes may
potentially increase the risk of postprandial hyperglycaemia
since they exhibited increased glucose absorption during hyper-
glycaemia, as evidenced by an increase in the glucose absorption
marker 3-O-methyl-glucose (3-OMG), compared with healthy
subjects. As SGLT1 is responsible for the active transport of
luminal 3-OMG, these studies confirm that TAS1R2 regulates
glucose absorption via SGLT1. The positive association found
between luminal glucose-induced changes in some sweet taste
receptor transcripts and the secretion of GLP-1 and GIP under-
scores that sweet taste receptors do have a regulatory role in the
release of incretins. Although these findings are supported by in
vitro studies, in vivo studies either in rodents or in humans
failed to show an effect of artificial sweeteners on the release of
satiation hormones, thereby questioning the role of sweet taste
receptors in incretin release.56 58 81–83 Nevertheless, chronic
exposure of high-fat fed diabetic mice with the artificial sweet-
ener, oligofructose, increased GLP-1 levels. Thus, the relative
importance of glucose transporters versus sweet taste receptors
in the release of incretins remains a matter of debate.
Glucose and insulin levels are remarkably normal in
TAS1R2−/− and TAS1R3−/− mice, despite the presence of sweet
taste ageusia in both genotypes. However, after an oral glucose
challenge TAS1R3−/− mice, but not TAS1R2−/− mice, showed
6 Depoortere I. Gut 2013;0:1–12. doi:10.1136/gutjnl-2013-305112
increased blood glucose and decreased insulin levels. The
TAS1R3−/− phenotype was less severe after an intraperitoneal
injection of glucose, indicating that some, but not all, of the
glucose dysregulation results from the disruption of normal gut
physiology. These findings are somewhat at variance with the
studies in patients with type 2 diabetes where a dysregulation of
TAS1R2 but not of TAS1R3 was observed during a luminal
glucose challenge and resulted in an increased glucose
absorption.
It is clear that the regulation of sweet taste receptors and
glucose transporters during different glycemic conditions is
complex. More studies using different models and conditions
are therefore warranted.
Gastric bypass
Gastric bypass surgery is one of the most effective methods for
inducing a marked and sustained weight loss in morbidly obese
patients. This procedure also results in amelioration or even
complete remission of type 2 diabetes mellitus independent
from weight loss.84 The mechanisms involved are incompletely
understood but involve restriction, malabsorption and humoral
changes. Indeed, bypass surgery decreases the release of the
orexigenic hormone, ghrelin, and increases the release of sati-
ation hormones PYY and GLP-1. After gastric bypass surgery,
the contact of nutrients with much of the stomach, duodenum
and part of the jejunum is bypassed. It can be hypothesised that
nutrient sensors on the ghrelin cell are isolated from contact
with nutrients thereby probably affecting ghrelin release and,
consequently, energy and glucose homeostasis. Additionally, the
rapid delivery of undigested nutrients to the lower small intes-
tine may affect the regulation of taste receptors and/or glucose
transporters on L-cells, resulting in enhanced release of PYY and
GLP-1. Indeed, duodenal–jejunal bypass surgery in a rat model
of type 2 diabetes decreased SGLT1 mRNA and
SGLT1-mediated transport in jejunum distal to the duodenojeju-
nostomy and improved diabetes independent from body weight
loss.85 A similar observation was made in non-obese mice after
duodenojejunal bypass surgery.86 Sweet taste receptors regulate
SGLT1 and a significant decrease in TAS1R2 and TAS1R3
protein levels in the alimentary limb after gastric bypass have
been demonstrated in rats.87 These results suggest that TAS1R3
antagonists or SGLT1 inhibitors may represent a promising
target for the treatment of obesity. In fact, LX4211, a dual intes-
tinal SGLT1/renal SGLT2 inhibitor increased GLP-1 levels and
PYY levels in patients with type 2 diabetes and improved blood
glucose levels and, therefore, mimicked the effects of gastric
bypass surgery.88 These results are inconsistent with studies
showing that SGLT1 is required for glucose-mediated GLP-1
release by L-cells in vitro.61 63 However, due to the carbohy-
drate malabsorption induced by SGLT1 inhibition, L-cells in the
colon also become glucose sensitive and increase GLP-1 levels.89
The authors suggested that this may be mediated by SCFAs pro-
duced by colonic fermentation of unabsorbed glucose that inter-
act with FFARs on L-cells to induce GLP-1 and PYY release. A
KATP channel-dependent mechanism involving an unknown
glucose sensor has also been suggested in glucose-induced
hindgut GLP-1 secretion during carbohydrate malabsorption.58
After gastric bypass surgery, patients show a decreased prefer-
ence for sweet and fatty foods, but the factors involved are
unclear. The decision of what to eat is modulated by taste, olfac-
tion and oral textural perception. Taste, in particular, has an
important input into food preference because it has direct
effects on brain reward circuits that drive eating. It has been sug-
gested that the acuity for sweet taste increases after gastric
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Recent advances in basic science

bypass, potentially leading to increased intensity of percep-
tion.90 It remains to be investigated whether endocrine cells in
the gut also show changes in sweet taste sensitivity after gastric
bypass surgery. Roux en-Y gastric bypass (RYGB) could further
reset the food reward system through changes in the release of
gut hormones, known to modify activity in brain reward
systems and dopaminergic signalling, but also known to modu-
late taste sensitivity in taste buds.91 92 Indeed, a recent study
showed that obese patients, after RYGB, had lower brain-
hedonic responses to food than patients after gastric banding.93
Additionally, aversive conditioning during the early postsurgical
period where unpleasant feelings (eg, dumping) associated with
particular foods can lead to conditioning of food aversion, may
also play a role.
Irritable bowel syndrome (IBS): FODMAPS and gluten
sensitivity
Patients with irritable bowel syndrome (IBS) claim that diet plays
a major role in triggering GI symptoms.94 The most common
approaches to manage food intolerance in IBS include: (1) the
low-FODMAP (fermentable, oligosaccharides disaccharides,
monosaccharides and polyols) diet, (2) the gluten-free diet, (3)
the elimination diet for food chemicals. How foods trigger func-
tional gut symptoms is unclear.
The low-FODMAP diet
Recent trials showed that dietary FODMAPs, especially fructose
and fructans, are dietary triggers for symptom generation, and
that restricting their level of intake might lead to durable
symptom improvement in patients with IBS.95 96 Two
mechanisms of action have been put forward for the FODMAP
diet: (1) FODMAPs are poorly absorbed in the small intestine
and are osmotically active, thereby drawing fluid through the
large bowel leading to diarrhoea97; (2) fermentation of the
FODMAPs in the colon will generate gases that may be incorpo-
rated in volatile end-products.98 The increase in fluid and gas
components will lead to luminal distension and may, in the pres-
ence of visceral hypersensitivity, induce bloating, flatulence,
abdominal pain and motility disturbances.
In this review, we speculate that alterations in nutrient-sensing
mechanisms may also play a role in symptom generation in
patients with IBS.
Altered short-chain fatty acid sensing?
Fermentation of FODMAPs, such as fructans, in the colon will
also result in the production of SCFAs, known to affect local
ion secretion99–101 and colonic motility.102 103 Indeed, intralum-
inal application of SCFA in the rat proximal colon accelerated
colonic transit by inducing the release of 5-HT that stimulates
5-HT3 receptors located on vagal sensory fibres, resulting in
muscle contraction via a vagal reflex pathway involving the
release of ACh from the myenteric plexus (figure 4).104 105 The
role of 5-HT in SCFAs-induced contractions was confirmed in
contractility studies with smooth muscle strips in vitro.106 In
fact, use of 5-HT3 antagonists has been shown to improve
symptoms in patients with IBS.107 We hypothesise that FFAR2
receptors on mucosal mast cells mediate the effect of SCFA on
5-HT release, since enterochromaffin cells and smooth muscle
cells do not contain FFARs (figure 4).74 75 Cremon et al108
showed that 5-HT release from mucosal biopsy specimens of

Figure 4 Proposed model for a role of altered short-chain fatty acid sensing that might contribute to symptom generation in patients with IBS in
response to ingestion of FODMAPs. Bacterial overgrowth in the small intestine of patients with IBS may result in the generation of short-chain fatty
acids (SCFAs) that may increase the sensitivity of FFAR2/3 on I-cells. The resulting increased release of CCK is known to alter intestinal motor activity
and to reduce pain thresholds in patients with IBS. In the colon, fermentation of fructans leads to the production of gases and SCFAs. Increased
FFAR2/3 sensing may enhance the secretion of GLP-1 and PYY from L-cells and 5-HT from mast cells, and may modulate visceral sensation and
motility by activation of extrinsic sensory neurons. ACh, acetylcholine; CCK, cholecystokinin; CCK1R, cholecystokinin 1 receptor; FFAR2/3, free fatty
acid receptor 2/3; FODMAPs, fermentable, oligosaccharides, disaccharides, monosaccharides and polyols; GLP-1, glucagon-like peptide 1; GLP-1 R,
glucagon-like peptide 1 receptor; 5-HT, 5-hydroxytryptamine; 5HT3, 5-hydroxytryptamine 3 receptor; IBS, irritable bowel syndrome; PYY, peptide YY;
SCFA, short-chain fatty acids; Y2R, Y2 receptor.

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Recent advances in basic science

patients with IBS was increased and correlated with mast cell
counts and the severity of the abdominal pain. It can be
hypothesised that in patients with IBS, alterations in the sensitiv-
ity or number of free fatty acid receptors involved in the
SCFA-induced release of 5-HT from mast cells, may play an
important role.
As already outlined, FFAR2 and FFAR3 sense SCFAs to affect
the release of gut peptides. Patients with IBS have increased
fasting and postprandial CCK levels.109 Isolated duodenal I-cells
are highly enriched in FFAR2 and FFAR3 mRNA transcripts.105
Under normal conditions these cells mainly sense circulating
SCFAs. The concept that small intestinal bacterial overgrowth is
a major pathogenic mechanism underlying IBS is still a matter
of debate.110–112 Nevertheless, in those patients with IBS with
bacterial overgrowth, luminal SCFA may also be sensed by the
I-cells and increase CCK secretion (figure 4). Infusion of CCK
in patients with IBS can lead to excessive intestinal motor activ-
ity and reduced pain thresholds.113 114
The postprandial PYY response is significantly increased in
hypersensitive compared to normosensitive patients with IBS.109
We propose that FFAR2 activation by SCFAs might be an import-
ant trigger for the release PYY/GLP-1 from colonic L-cells (figure
4). Indeed, feeding rats a fructo-oligosaccharide-enriched diet
selectively induced the proliferation of FFAR2-positive
L-cells.115 Additionally, colonic infusion of SCFA stimulated PPY
release in rats. Immunoneutralisation of circulating PYY abolished
the effect of SCFA on colonic motility while the effect was mim-
icked by exogenous PYY infusion.116 In FFAR3−/− mice, charac-
terised by a decrease in PYY expression, intestinal transit rate was
increased.117
In conclusion, the low FODMAP diet might also improve
symptoms by reducing the levels of SCFAs that act via FFAR2,
FFAR3 and transporters to affect ion secretion and GI motility
by releasing hormones and neurotransmitters. Studies are war-
ranted to investigate whether alterations in the number or sensi-
tivity of these FFARs occur in patients with IBS. If so, FFAR2
and FFAR3 antagonists, currently under development, may
therefore become promising tools for the treatment of IBS.118
Since SCFAs induce neutrophil chemotaxis through FFAR2, a
low FODMAP diet or FFAR2 antagonists may, therefore, also
help to control inflammation in subsets of patients with IBS
with low-grade inflammation.119
Altered carbohydrate sensing?
Effects observed in TAS1R3−/− and GLUT5−/− mice mimic the
effects observed in patients with IBS. Due to duodenal carbohy-
drate malabsorption, both genotypes display a distended prox-
imal colon with the development of gas pockets as a result of
subsequent fermentation by intestinal microflora.58 120
Additionally, the increased carbohydrate content in the colon of
TAS1R3−/− mice, induced robust glucose-induced GLP-1 secre-
tion from the colon which may induce alterations in transit
(figure 5). Fructose interacts with TAS1R3 and GLUT5.58 120
We hypothesise that the fructose malabsorption in some patients
with IBS may be due to alterations in the basal expression of
TAS1R3 and GLUT5 or in their regulation in response to
dietary fructose. Therefore, future studies are warranted to
investigate the mechanisms of altered glucose sensing in patients
with IBS.
The gluten-free diet
Gluten is a well known trigger for GI symptoms in the setting
of coeliac disease. The existence of gluten intolerance was
demonstrated in patients with IBS without celiac disease.121

Figure 5 Possible role of changes in carbohydrate sensing that may contribute to symptom generation in patients with IBS in response to
ingestion of FODMAPs. Decreased expression or sensitivity of sweet taste receptors and/or concomitant alterations in GLUT5 expression may
contribute to fructose malabsorption in patients with IBS. Due to the increased carbohydrate content in the colon, the L-cells become glucose
sensitive through a sweet taste receptor-independent pathway involving closure of KATP channels and influx of Ca2+ through voltage-gated Ca2+
channels. The resulting increase in GLP-1 release may induce changes in transit due to the ileal brake effect. ATP, adenosine triphosphate;
FODMAPs, fermentable oligosaccharides, disaccharides, monosaccharides and polyols; GLP-1, glucagon-like peptide 1; GLUT2, glucose transporter 2;
GLUT5, glucose transporter 5; KATP, ATP-sensitive potassium channel; TAS1R2, taste receptor type 1 member 2; TAS1R3, taste receptor type 1
member 3; SGLT1, sodium-dependent glucose transporter.

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However, the same authors recently reported that gluten might
not be a specific trigger of functional gut symptoms once
dietary FODMAPs are reduced.122 Another controlled trial of
gluten-free diet showed that gluten alters small bowel perme-
ability in diarrhoea-predominant patients with IBS, particularly
in HLA-DQ2/8-positive patients.123 This may result in greater
fluid flux toward the lumen and may elicit immune responses
that affect afferent nerves resulting in hypersensitivity.
Altered glutamate sensing?
Glutamic acid (Glu) and proline together account for one half
or more of the peptide-bound amino acids in gluten. Ingestion
of a protein diet rich in L-Glu does not lead to appreciable
changes in plasma glutamate concentrations, since glutamate is
extensively metabolised by enterocytes and does not reach the
portal vein.124 Thus, once proteins such as wheat are digested,
dietary Glu may stimulate Glu sensors (e.g TAS1R -TAS1R3,
CaSR and metabotropic glutamate receptors (mGluR)) in the
stomach and intestine producing local effects on gut function.
For example, in dogs, intragastric, but not intraduodenal,
administration of monosodium glutamate (MSG) stimulated
gastric emptying and induced phasic non-propagating contrac-
tions in the upper gut which were blocked by vagotomy.125
Contradictory results have been reported concerning the effect
of MSG on gastric emptying in humans.126 127
Among 20 natural amino acids investigated, only L-Glu
evoked firing of afferent fibres of the vagal gastric branch in
rats. The effect is mediated via metabotropic L-Glu receptors
that induce the release of 5-HT from mucosal cells interacting
with 5-HT3 receptors on afferent fibres.128 Additionally, intra-
gastric infusion of Glu activated brain regions that are directly
or indirectly targeted by these vagal inputs.129 Nevertheless, the
effect of glutamate on vagal afferent firing seems not to be
straightforward, since inhibitory effects of exogenous and
endogenous glutamate have been reported on vagal afferent
mechanosensitivity involving group II (mGluR2 and 3) and
group III mGluR (mGlu R4, 6, 7, 8).130
In view of the beneficial effects that are observed with a
gluten-free diet in patients with IBS, we hypothesise that altera-
tions in luminal glutamate sensing may occur that affect vagal
nerve activity resulting in altered brain–gut interactions and
symptom generation.
The elimination diet for food chemicals
The elimination diet involves restriction of common food aller-
gens, specific chemical substances in foods or medications that
contain these chemicals.
Coffee is commonly reported as a trigger for symptoms in
patients with IBS.131 It is not clear whether salicylates or caf-
feine in coffee are the triggers but both components taste bitter
and could alter gut function via TAS2Rs.
Functional dyspepsia
According to the Rome III classification, functional dyspepsia
can be divided into two categories: postprandial distress syn-
drome and epigastric pain syndrome, suggesting that at least in
some patients the disorder is related to food ingestion. While
most of the patients report that their symptoms are triggered
within 30 min after meal ingestion, few studies have been per-
formed to evaluate the role of specific foods.132 Particularly,
meals containing fat seem to induce or exacerbate symptoms.133
Pilichiewicz et al134 reported that ingestion of a high-fat meal,
but not of a high-carbohydrate meal, was associated with a sub-
stantially greater increase in nausea and pain immediately after
Depoortere I. Gut 2013;0:1–12. doi:10.1136/gutjnl-2013-305112
Recent advances in basic science
completion of ingestion. Furthermore the scores for nausea and
pain were related directly to the increased plasma CCK concen-
trations in patients with functional dyspepsia. It is known that
exogenous CCK administration can mimic dyspeptic symp-
toms.135 It is therefore conceivable that similar to patients with
IBS, who frequently overlap with functional dyspepsia patients,
alterations in the expression or sensitivity of free fatty acid
receptors on endocrine cells may render them more sensitive to
dietary fat and exacerbate symptoms.136 Diet-intervention
studies, similar to what has been performed in patients with
IBS, are warranted to investigate the role of nutrients and,
hence, of taste receptors in symptom generation in patients with
functional dyspepsia.
CONCLUSIONS AND PERSPECTIVES
The observation, and now compelling evidence, for the pres-
ence and function of taste receptors in extraoral tissues offers
exciting new possibilities for targeted therapeutics in the battle
against diseases of and involving the GI tract. Several taste
receptor families involved in nutrient sensing in the gut offer
potential advantages as drug targets.
Sweet taste receptors
This long history of sweetener chemistry suggests that new com-
pounds of exceptional specificity and high efficacy could be
designed. The beneficial effects of artificial sweeteners in the
control of body weight and glucose homeostasis are still a
matter of debate, but advances in our understanding of the
sweet taste receptor biology may therefore help to design new
artificial sweeteners with favourable effects.137 Indeed, in con-
trast with in vitro studies, in vivo studies either in rodents or in
humans failed to show an effect of artificial sweeteners on the
release of satiation hormones. 56 58 81–83 Advances in our under-
standing of the sweet taste receptor biology may therefore help
to design new artificial sweeteners with favourable effects.
However, their effectiveness may be complicated by the
complex interaction between sweet taste receptors and glucose
transporters that cross-regulate each other’s expression.
Additionally, the evidence provided for altered sweet taste recep-
tor control in type 2 diabetes may open new opportunities for
drugs that interfere with sweet taste receptor regulation.
In gastric bypass patients, additional studies should help to
provide insight to what the effect is of shunting nutrients to
more distal regions of the gut in the control of taste receptor
expression/glucose transporter regulation, and the release of
hormones involved in the regulation of energy and glucose
homeostasis. It is tempting to speculate that targeting these
receptors/transporters may mimic the effects of gastric bypass
surgery in a non-surgical manner. In fact, ongoing trials with
SGLT1 inhibitors already show promising results.88
Bitter taste receptors
Evidence suggests that bitter agonists could be considered as
good targets to reduce hunger and motility.18 22 32 However,
the design of new bitter drugs may be complicated by the fact
that in humans, 25 receptor subtypes exist, each with different
ligand selectivities and a different distribution pattern.
Nevertheless, there are also some opportunities. Thousands of
plant-derived bitter tastants and metabolites are available that
could be tested in appropriate physiological models to select
those with favourable therapeutic profiles.
9
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Recent advances in basic science
Amino acid and free fatty acid receptors
Recent evidence suggests that food choice (low FODMAPs,
gluten-free diet) is a key management strategy for the treatment
of symptoms in patients with IBS. These studies underscore
claims made for many years by alternative practitioners. The
mechanisms involved are not completely understood, but indir-
ect evidence suggests that altered carbohydrate sensing, exacer-
bated sensing of SCFAs by FFARs or of Glu by amino acid
receptors may be involved. Determining alterations in basal
expression levels of these receptors or in their regulation in
response to a diet may help to provide a rationale for the use of
FFAR antagonists or Glu receptor antagonists in these patients
and may help to predict whether a patient will be responsive to
the diet or not. Similar strategies may be useful in patients with
functional dyspepsia.
It is clear that the existence and functional role of taste recep-
tors in the gut is a new and fascinating field of research that
may lead to the development of new therapeutic drugs that may
benefit from the progress made in our understanding of taste
receptor function in the tongue.
Acknowledgements The author wishes to thank S. Munger for providing helpful
discussion.
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.
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Taste receptors of the gut: emerging roles in

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Inge Depoortere

Gut published online October 16, 2013

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