Search

Human taste cells are a heterogeneous population of specialized epithelial cells that are constantly generated from progenitor taste cells. Type I and type III taste cells express some neural markers, and studies have reported that direct innervation by neurons is not required for taste cell development. To our knowledge, no previous study has demonstrated that taste cells can differentiate into neuron-like cells or any other non-taste cell type. Here, for the first time, we describe a simple in vitro method that uses a serum-free neural induction medium to differentiate cultured physiologically functional primary human taste (HBO) cells into neuron-like cells in 2-3 wk with high efficiency. We verified neural attributes of these HBO-derived neuron-like with immunocytochemistry, single-cell calcium imaging, and DiI staining and examined cell morphology using transmission electron microscopy. Induced neuron-like cells demonstrated neuron-specific proteins, dendritic and axonal morphology, and networking behaviors. This technique will open new avenues for translational medicine, autologous cell therapy, regenerative medicine, therapy for neurodegenerative disorders, and drug screening.

Tongue fungiform papillae contain taste buds crucial for taste and hormone-producing taste receptor cells; therefore, they may be considered as endocrine organs and have important age-associated physiological implications. We examine the cross-sectional and longitudinal trajectories of fungiform papillae density in 1084 participants from the Baltimore Longitudinal Study of Aging using linear regression models and mixed effects models. At baseline, the mean age was 67.86 ± 14.20 years, with a mean follow-up time among those with repeat visits of 4.24 ± 1.70 years. Women (53%) were younger (66.85 ± 13.78 vs. 69.04 ± 14.61 years, p < 0.001) and had a higher fungiform papillae density than men (16.14 ± 9.54 vs. 13.77 ± 8.61 papillae/cm2, p < 0.001). Whites (67%) had a lower fungiform papillae density than non-Whites after adjusting for age and sex. Factors cross-sectionally associated with a lower fungiform papillae density included a higher waist-hip ratio (β = −8.525, p = 0.029), current smoking status (β = −5.133, p = 0.014), and alcohol use within the past 12 months (β = −1.571, p = 0.025). Longitudinally, fungiform papillae density decreased linearly with follow-up time (β = −0.646, p < 0.001). The rate of decline was not affected by sex, race, BMI, waist-hip ratio, smoking, or alcohol use. The longitudinal decline of fungiform papillae density over time needs to be explored further in order to identify other possible age-associated physiological determinants.

Food compounds with a bitter taste have a role in human health, both for their capability to influence food choice and preferences and for their possible systemic effect due to the modulation of extra-oral bitter taste receptors (TAS2Rs). Investigating the interaction of bitter food compounds with TAS2Rs is a key step to unravel their complex effects on health and to pave the way to rationally design new additives for food formulation or drugs. Here, we propose a collection of food bitter compounds, for which in vitro activity data against TAS2Rs are available. The patterns of TAS2R subtype-specific agonists were analyzed using scaffold decomposition and chemical space analysis, providing a detailed characterization of the associations between food bitter tastants and TAS2Rs.

Taste and smell play a key role in our ability to perceive foods. Overconsumption of highly palatable energy-dense foods can lead to increased caloric intake and obesity. Thus there is growing interest in the study of the biological mediators of fat taste and associated olfaction as potential targets for pharmacologic and nutritional interventions in the context of obesity and health. The number of studies examining mechanisms underlying fat taste and smell has grown rapidly in the last 5 years. Therefore, the purpose of this systematic review is to summarize emerging evidence examining the biological mechanisms of fat taste and smell. A literature search was conducted of studies published in English between 2014 and 2021 in adult humans and animal models. Database searches were conducted using PubMed, EMBASE, Scopus, and Web of Science for key terms including fat/lipid, taste, and olfaction. Initially, 4,062 articles were identified through database searches, and a total of 84 relevant articles met inclusion and exclusion criteria and are included in this review. Existing literature suggests that there are several proteins integral to fat chemosensation, including cluster of differentiation 36 (CD36) and G protein-coupled receptor 120 (GPR120). This systematic review will discuss these proteins and the signal transduction pathways involved in fat detection. We also review neural circuits, key brain regions, ingestive cues, postingestive signals, and genetic polymorphism that play a role in fat perception and consumption. Finally, we discuss the role of fat taste and smell in the context of eating behavior and obesity.

Zinc is an essential trace element, and its deficiency causes taste dysfunction. Zinc accumulates in zinc transporter (ZnT)3-expressing presynaptic vesicles in hippocampal neurons and acts as a neurotransmitter in the central nervous system. However, the distribution of zinc and its role as a signal transmitter in taste buds remain unknown. Therefore, we examined the distribution of zinc and expression profiles of ZnT3 in taste cells and evaluated zinc release from isolated taste cells upon taste stimuli. Taste cells with a spindle or pyriform morphology were revealed by staining with the fluorescent zinc dye ZnAF-2DA and autometallography in the taste buds of rat circumvallate papillae. Znt3 mRNA levels were detected in isolated taste buds. ZnT3-immunoreactivity was found in phospholipase-β2-immunopositive type II taste cells and aromatic amino acid decarboxylase-immunopositive type III cells but not in nucleoside triphosphate diphosphohydrolase 2-immunopositive type I cells. Moreover, we examined zinc release from taste cells using human transient receptor potential A1-overexpressing HEK293 as zinc-sensor cells. These cells exhibited a clear response to isolated taste cells exposed to taste stimuli. However, pretreatment with magnesium-ethylenediaminetetraacetic acid, an extracellular zinc chelator - but not with zinc-ethylenediaminetetraacetic acid, used as a negative control - significantly decreased the response ratio of zinc-sensor cells. These findings suggest that taste cells release zinc to the intercellular area in response to taste stimuli and that zinc may affect signaling within taste buds.

Amino acids contribute to the taste of foods. Previous studies on the taste of amino acids focused mainly on α-amino acids, and therefore, the taste characteristics of amino acid derivatives remain unclear. In the present study, we targeted 6 different amino acid derivatives, β-alanine, citrulline, creatine, γ-aminobutyric acid, taurine, and ornithine, and evaluated their taste characteristics in a human sensory study. All tested amino acid derivatives showed multiple taste qualities; no derivatives had only a single taste quality. However, their taste intensities were relatively weak even at high concentrations. Given that the interactions between amino acid derivatives and nucleotide result in taste enhancements, we investigated the effect of inosine 5'-monophosphate (IMP) on the taste characteristics and found that the taste intensity of ornithine increased in the presence of IMP. This finding will be useful for understanding the role of amino acid derivatives as taste substances in daily foods.

The gustatory system detects and informs us about the nature of various chemicals we put in our mouth. Some of these have nutritive value (sugars, amino acids, salts, and fats) and are appetitive and avidly ingested, whereas others (atropine, quinine, nicotine) are aversive and rapidly rejected. However, the gustatory system is mainly responsible for evoking the perception of a limited number of qualities that humans taste as sweet, umami, bitter, sour, salty, and perhaps fat [free fatty acids (FFA)] and starch (malto-oligosaccharides). The complex flavors and mouthfeel that we experience while eating food result from the integration of taste, odor, texture, pungency, and temperature. The latter three arise primarily from the somatosensory (trigeminal) system. The sensory organs used for detecting and transducing many chemicals are found in taste buds (TBs) located throughout the tongue, soft palate esophagus, and epiglottis. In parallel with the taste system, the trigeminal nerve innervates the peri-gemmal epithelium to transmit temperature, mechanical stimuli, and painful or cooling sensations such as those produced by changes in temperature as well as from chemicals like capsaicin and menthol, respectively. This article gives an overview of the current knowledge about these TB cells' anatomy and physiology and their trigeminal induced sensations. We then discuss how taste is represented across gustatory cortices using an intermingled and spatially distributed population code. Finally, we review postingestion processing (interoception) and central integration of the tongue-gut-brain interaction, ultimately determining our sensations as well as preferences toward the wholesomeness of nutritious foods. © 2021 American Physiological Society. Compr Physiol 11:1-35, 2021.

Taste is one of the essential senses in providing the organism a faithful representation of the external world. Taste perception is responsible for basic food and drink appraisal and bestows the organism with valuable discriminatory power. Umami and sweet are "good" tastes that promote consumption of nutritive food, whereas bitter and sour are "bad" tastes that alert the organism to toxins and low pH, promoting rejection of foods containing harmful substances. Not every animal has the same sense of taste as humans. Variation in the taste receptor genes contributes to inter and intra organism differences of taste (sweet/bitter) sensation and preferences. Therefore a deeper understanding was needed to comprehend taste perception by various vertebrates and accordingly elucidate a possible proximity among them. In this study, a total 20 Type-1 (sweet) and 189 Type-2 (bitter) taste receptor complete-amino acid sequences were taken from the 20 vertebrate organisms (18 mammalian, 1 Aves, and 1 amphibian). Among 10 primates, 8 including humans were very close based on genomics of taste receptors and rodent organisms viz. the rat and mouse were away from them. This investigation throws light on the similitude and dissimilitude of perception of sweet and bitter taste among 20 different organisms, steered by quantitative analysis of their genomic data. Furthermore, it enlightened that ligand binding affinity of sweet/bitter taste molecules in the taste receptors of any proximal pair of organisms would be similar.

Bitter taste receptors (T2Rs) are G protein-coupled receptors involved in the perception of bitter taste on the tongue. In humans, T2Rs have been found in several sites outside the oral cavity. Although T2R38 has been reported to be expressed on peripheral lymphocytes, it is poorly understood whether T2R38 plays immunological roles in inflammatory skin diseases such as atopic dermatitis (AD). Then, we first confirmed that T2R38 gene expression was higher in lesional skin of AD subjects than healthy controls. Furthermore, skin T2R38 expression levels were correlated with serum thymus and activation-regulated chemokine and IgE levels in AD patients. In lesional skin of AD, section staining revealed that CD3+ T cells in the dermis were T2R38 positive. In addition, flow cytometry analysis showed T2R38 expression in skin T cells. Migration assays using T2R38-transduced Jurkat T cell leukemia cells revealed that T2R38 agonists exerted a dose-dependent migration inhibitory effect. Moreover, skin tissue extracts, as well as supernatants of cultured HaCaT keratinocytes, caused T2R38-dependent migration inhibition, indicating that there should be an endogenous ligand for T2R38 in the skin epidermis. These findings implicate T2R38 as a migratory inhibitory receptor on the skin-infiltrating lymphocytes and as a therapeutic target for allergic/inflammatory skin diseases.

Purpose of Review From single cells to entire organisms, biological entities are in constant communication with their surroundings, deciding what to ‘allow’ in, and what to reject. In very different ways, the immune and taste systems both fulfill this function, with growing evidence suggesting a relationship between the two, through shared signaling pathways, receptors, and feedback loops. The purpose of this review was to explore recent reports on taste and immunity in model animals and in humans to explore our understanding of the interplay between these systems. Recent Findings Acute infections in the upper airway, as with SARS-CoV-2, are associated with a proinflammatory state, and blunted taste perception. Further, recent findings highlight taste receptors working as immune sentinels throughout the body. Work in humans and mice also points to inflammation from obesity impacting taste, altering taste bud abundance and composition. Summary There is accumulating evidence that taste cells, and particularly their receptors, play a role in airway and gut immunity, responsive to invading organisms. Inflammation itself may further act on taste buds and other taste receptor expressing cells throughout the body as a form of homeostatic control.

In addition to the α, β, and γ subunits of ENaC, human salt-sensing taste receptor cells (TRCs) also express the δ-subunit. At present, it is not clear if the expression and function of the ENaC δ-subunit in human salt-sensing TRCs is also modulated by the ENaC regulatory hormones and intracellular signaling effectors known to modulate salt responses in rodent TRCs. Here, we used molecular techniques to demonstrate that the G-protein-coupled estrogen receptor (GPER1), the transient receptor potential cation channel subfamily V member 1 (TRPV1), and components of the renin-angiotensin-aldosterone system (RAAS) are expressed in δ-ENaC-positive cultured adult human fungiform (HBO) taste cells. Our results suggest that RAAS components function in a complex with ENaC and TRPV1 to modulate salt sensing and thus salt intake in humans. Early, but often prolonged, symptoms of COVID-19 infection are the loss of taste, smell, and chemesthesis. The SARS-CoV-2 spike protein contains two subunits, S1 and S2. S1 contains a receptor-binding domain, which is responsible for recognizing and binding to the ACE2 receptor, a component of RAAS. Our results show that the binding of a mutated S1 protein to ACE2 decreases ACE2 expression in HBO cells. We hypothesize that changes in ACE2 receptor expression can alter the balance between the two major RAAS pathways, ACE1/Ang II/AT1R and ACE2/Ang-(1–7)/MASR1, leading to changes in ENaC expression and responses to NaCl in salt-sensing human fungiform taste cells.

Differences in the ability to identify and perceive tastes and smells might influence food consumption and, ultimately, chronic nutrition-related conditions such as overweightness and obesity. This study aimed to investigate the associations between taste sensitivity and odour function, anthropometry, and quantity of fungiform papillae in children at age 11–15. Taste strips (4 base tastes), U-Sniff sticks (12 selected smells), and a filter paper strip impregnated with 6-n-propylthiouracil (PROP) were used. The photographic method was used to estimate the number of fungiform papillae (FP) on the tongue. The results showed that the quantity of FP was not related to anthropometry or gender. The taste test total scores were higher for girls, for whom the median score was 14 (12.0–15.0), than for boys, for whom the median score was 12 (9.0–13.0). Of the children, 13.9% had some difficulty in identifying odours. The Mann–Whitney U test showed that children who were most sensitive to bitter taste had more FP (p = 0.0001). The median score for this group (score = 4) was 34.0 (27.0–37.0). For those who had some problems with correctly assessing all bitter taste strips (score = 0–3), the median score was 24.0 (20.0–31.0). Higher numbers of FP were also observed in tasters, that is, people sensitive to PROP, than in nontasters. Only some measures of the taste function correlated with each other, but not very significantly. We concluded that there are multiple perceptual phases of taste, with no single measure able to entirely represent the sense of taste.

Originally identified on the tongue for their chemosensory role, the receptors for sweet, umami, and bitter taste are expressed in some cancers where they regulate important cellular processes including apoptosis and proliferation. We examined DNA mutations (n = 5103), structural variation (n = 7545), and expression (n = 6224) of genes encoding sweet or umami receptors (TAS1Rs) and bitter receptors (TAS2Rs) in 45 solid tumors subtypes compared to corresponding normal tissue using The Cancer Genome Atlas and the Genotype Tissue Expression Project databases. Expression of TAS1R and TAS2R genes differed between normal and cancer tissue, and nonsilent mutations occurred in many solid tumor taste receptor genes (~ 1–7%). Expression levels of certain TAS1Rs/TAS2Rs were associated with survival differences in 12 solid tumor subtypes. Increased TAS1R1 expression was associated with improved survival in lung adenocarcinoma (mean survival difference + 1185 days, p = 0.0191). Increased TAS2R14 expression was associated with worse survival in adrenocortical carcinoma (−1757 days, p p = 0.0041), but improved survival in non-papillary bladder cancer (+ 343 days, p = 0.0436). Certain taste receptor genes may be associated with important oncologic pathways and could serve as biomarkers for disease outcomes.

The chapter presents an argument supporting the view that taste, defined as the receptor-mediated signaling of taste cells and consequent sensory events, is proper subject matter for the field of pharmacology. The argument develops through a consideration of how the field of pharmacology itself is to be defined. Though its application toward the discovery and development of therapeutics is of obvious value, pharmacology nevertheless is a basic science committed to examining biological phenomena controlled by the selective interactions between chemicals - regardless of their sources or uses - and receptors. The basic science of pharmacology is founded on the theory of receptor occupancy, detailed here in the context of taste. The discussion then will turn to consideration of the measurement of human taste and how well the results agree with the predictions of receptor theory.

COVID-19, a recently emerged disease caused by SARS-CoV-2 infection, can present with different degrees of severity and a large variety of signs and symptoms. The oral manifestations of COVID-19 often involve the tongue, with loss of taste being one of the most common symptoms of the disease. This study aimed to detect SARS-CoV-2 RNA and assess possible morphological and immunopathological alterations in the lingual tissue of patients who died with a history of SARS-CoV-2 infection. Sixteen cadavers from 8 SARS-CoV-2 positive (COVID-19+) and 8 negative (COVID-19−) subjects provided 16 tongues, that were biopsied. Samples underwent molecular analysis through Real-Time RT-PCR for the detection of SARS-CoV-2 RNA. Lingual papillae were harvested and processed for histological analysis and for immunohistochemical evaluation for ACE2, IFN-γ and factor VIII. Real-Time RT-PCR revealed the presence of SARS-CoV-2 RNA in filiform, foliate, and circumvallate papillae in 6 out of 8 COVID-19+ subjects while all COVID-19− samples resulted negative. Histology showed a severe inflammation of COVID-19+ papillae with destruction of the taste buds. ACE2 and IFN-γ resulted downregulated in COVID-19+ and no differences were evidenced for factor VIII between the two groups. The virus was detectable in most COVID-19+ tongues. An inflammatory damage to the lingual papillae, putatively mediated by ACE2 and IFN-γ in tongues from COVID-19+ cadavers, was observed. Further investigations are needed to confirm these findings and deepen the association between taste disorders and inflammation in SARS-CoV-2 infection.

Understanding taste is key for optimizing the palatability of seaweeds and other non-animal-based foods rich in protein. The lingual papillae in the mouth hold taste buds with taste receptors for the five gustatory taste qualities. Each taste bud contains three distinct cell types, of which Type II cells carry various G protein-coupled receptors that can detect sweet, bitter, or umami tastants, while type III cells detect sour, and likely salty stimuli. Upon ligand binding, receptor-linked intracellular heterotrimeric G proteins initiate a cascade of downstream events which activate the afferent nerve fibers for taste perception in the brain. The taste of amino acids depends on the hydrophobicity, size, charge, isoelectric point, chirality of the alpha carbon, and the functional groups on their side chains. The principal umami ingredient monosodium l-glutamate, broadly known as MSG, loses umami taste upon acetylation, esterification, or methylation, but is able to form flat configurations that bind well to the umami taste receptor. Ribonucleotides such as guanosine monophosphate and inosine monophosphate strongly enhance umami taste when l-glutamate is present. Ribonucleotides bind to the outer section of the venus flytrap domain of the receptor dimer and stabilize the closed conformation. Concentrations of glutamate, aspartate, arginate, and other compounds in food products may enhance saltiness and overall flavor. Umami ingredients may help to reduce the consumption of salts and fats in the general population and increase food consumption in the elderly.

Background: Although duodenal diverticula are associated with less frequent pathology than the colonic diverticula in the large intestine, their periampullary position may have significant clinical implications. The aim of the study was to identify any possible correlation between the type of localisation of the major duodenal papilla, duodenal diverticula, and some particular clinical issues. Materials and methods: In total, 628 patients (408 females and 220 males; aged 21–91 years), who underwent endoscopic retrograde cholangiopancreatography were included in this study. The patients were divided into two groups: a study group comprising 66 (10.5%) patients with periampullary position of diverticula (group A), and a control group comprising 562 (89.5%) patients without diverticula (group B). Results: A duodenal diverticulum was diagnosed in the periampullary position in 66/628 (10.5%) patients: 41 women (aged 52–91 years) and 25 men (aged 54–83 years). Conclusions: Three types of localisation were observed for the major duodenal papilla with regard to the diverticula, with the most common type being next to each other (type III). In patients with diverticula, similar frequencies of gallstone occurrence are observed in men and women. Patients with papilla in the diverticulum who underwent cholecystectomy are more prone to develop lithiasis.

This study investigated the individual variability in oral tactile sensitivity considering touch, by means of Von Frey Hair monofilaments (VFH) and spatial resolution, using the grating orientation test (GOT). The relationships of the two measures with 6-n-propylthiouracil (PROP) responsiveness and fungiform papillae density and size were investigated. One hundred and forty-four subjects (48.6% women, aged 18-30) participated in the study. VFH and GOT thresholds were assessed by three-down/one-up staircase method. Responsiveness to 3.2 mM PROP was assessed on the general Labeled Magnitude Scale. Fungiform papillae density (FPD) and size were determined from automated counting. VFH thresholds appeared unsuitable to reveal individual variation in responsiveness to point-pressure on the tongue. The frequency of GOT thresholds approximated a normal distribution and covered the whole range of variation, thus indicating an ability to measure individual variation in oral tactile sensitivity. No significant linear correlations were found between any of the oral tactile sensitivity measures and PROP responsiveness, FPD total and size class. VFH and GOT thresholds were not significantly associated. Agglomerative hierarchical clustering was used to classify participants for their PROP responsiveness, total FPD and GOT threshold. Three clusters were identified, C1 (n = 67), Cl2 (n = 42), and Cl3 (n = 35), differing for PROP responsiveness and FPD only. Results encourage future studies to explore association between GOT and both perception and preference for different food texture. Furthermore, deeper investigation of individual variability in sensitivity to different types of oral tactile stimuli would be helpful to capture differences in tactile sensitivity among the most sensitive individuals.

Obesity is characterized by chronic low-grade inflammation that could lead to other health complications, such as cardiovascular disease, diabetes, and various forms of cancer. Emerging evidence has shown that taste perception is altered during the development of obesity. Moreover, suppression of taste receptor or taste signaling molecules potentiate the inflammatory response, and the progression of inflammation attenuates the expression of taste receptors in vivo. Together, these findings suggest a possible interplay between taste signaling and inflammation. This review summarizes the interactions between type 1 (T1Rs) and type 2 taste receptors (T2Rs) and inflammation, as well as the impact of obesity on T1R- and T2R-mediated signaling. Furthermore, we evaluate the possible role that taste receptors play in regulating the inflammatory response during obesity as a therapeutic target to prevent the progression of comorbidities associated with obesity.

Several studies have used taste sensitivity to 6-n-propylthiouracil (PROP) to evaluate interindividual taste variability and its impact on food preferences, nutrition, and health. We used a supervised learning (SL) approach for the automatic identification of the PROP taster categories (super taster (ST); medium taster (MT); and non-taster (NT)) of 84 subjects (aged 18–40 years). Biological features determined from subjects were included for the training system. Results showed that SL enables the automatic identification of objective PROP taster status, with high precision (97%). The biological features were classified in order of importance in facilitating learning and as prediction factors. The ratings of perceived taste intensity for PROP paper disks (50 mM) and PROP solution (3.2 mM), along with fungiform papilla density, were the most important features, and high estimated values pushed toward ST prediction, while low values leaned toward NT prediction. Furthermore, TAS2R38 genotypes were significant features (AVI/AVI, PAV/PAV, and PAV/AVI to classify NTs, STs, and MTs, respectively). These results, in showing that the SL approach enables an automatic, immediate, scalable, and high-precision classification of PROP taster status, suggest that it may represent an objective and reliable tool in taste physiology studies, with applications ranging from basic science and medicine to food sciences.

Sensitivity of the somatosensory system may be influenced by multiple physiological parameters. Variations in oral physiology can arise from cross-cultural differences which may potentially affect sensory sensitivity. The aim of this case study was to quantify texture and taste sensitivity in Dutch (Caucasian) and Chinese (Asian) adults living in the Netherlands. Eighty-five healthy subjects were recruited including 44 Dutch (Caucasian) adults (29 females, 22.8 ± 2.3 yrs) and 41 Chinese (Asian) adults (30 females, 24.5 ± 2.1 yrs) living in the Netherlands for less than 1 year. Three sets of stimuli were used to quantify sensitivity of thickness (maltodextrin solutions differing in viscosity), firmness (agar gels differing in fracture stress) and sweetness (sucrose solutions differing in concentration). The 2-Alternative Forced Choice (2-AFC) ascending staircase method was used to determine texture and taste sensitivity. Unstimulated and stimulated saliva flow rate, fungiform papillae density (FPD), lingual tactile threshold and PROP taster status were determined and are referred to as physiological and sensory consumer characteristics. No significant differences were observed between Chinese and Dutch adults for thickness (Dutch 2.60 mPas, Chinese 2.19 mPas), firmness (Dutch 10.5 kPa, Chinese 10.3 kPa) and sweetness sensitivity (Dutch 0.012 g/mL, Chinese 0.017 g/mL). No significant differences were observed between Chinese and Dutch adults for saliva flow rate, lingual tactile threshold and PROP taster status. The relationships between the three sensory sensitivities (thickness, firmness, sweetness) and five physiological and sensory consumer characteristics (unstimulated and stimulated saliva flow rate, FPD, lingual tactile threshold, PROP taster status) were analyzed. Only one out of 15 relationships, firmness sensitivity and FPD, was significantly and weakly related suggesting that inter-individual variation in these consumer characteristics is almost unrelated to sensory sensitivity. We conclude that in this case study thickness, firmness and sweetness sensitivities do not differ between Dutch and Chinese adults living in the Netherlands. Saliva flow rate, fungiform papillae density, lingual tactile threshold and PROP taster status do not explain inter-individual variation in sensory sensitivity between these consumers.

Bitterness is perceived in humans by 25 subtypes of bitter taste receptors (hTAS2R) that range from broadly tuned to more narrowly tuned receptors. hTAS2R5 is one of the most narrowly tuned bitter taste receptors in humans. In this study, we review the literature on this receptor and show there is no consensus about its role. We then compare the possible role of hTAS2R5 with that of the proteins of the TAS2R family in rat, mouse, and pig. A phylogenetic tree of all mammalian TAS2R domain-containing proteins showed that human hTAS2R5 has no ortholog in pig, mouse, or rat genomes. By comparing the agonists that are common to hTAS2R5 and other members of the family, we observed that hTAS2R39 is the receptor that shares most agonists with hTAS2R5. In mouse, some of these agonists activate mTas2r105 and mTas2r144, which are distant paralogs of hTAS2R5. mTas2r144 seems to be the receptor that is most similar to hTAS2R5 because they are both activated by the same agonists and have affinities in the same range of values. Then, we can conclude that hTAS2R5 has a unique functional specificity in humans as it is activated by selective agonists and that its closest functional homolog in mouse is the phylogenetically distant mTas2r144. This research was funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa”, grant number AGL2017-83477-R, C. Grau-Bové received a doctoral research grant from the Martí Franqués program of the Universitat Rovira i Virgili. M. Pinent and X. Terra are Serra Húnter fellows. We would like to express our thanks to Judith Pérez for her contribution to this work.

The prototypical stimuli for umami taste is monosodium glutamate (MSG), which is the sodium salt form of glutamic acid. A proportion of the population has a reduced or complete inability to taste l-glutamate independent to the sodium ion. To determine individuals’ umami discrimination status, many studies use a series of triangle tests containing isomolar (29 mM) sodium chloride (NaCl) and MSG, requiring participants to correctly identify the odd sample. Across studies, inconsistent categorization criteria have been applied. The aim of this study was to determine the optimal classification criterion based on the number of tests assessed to ascertain an individual’s ability to discriminate between MSG and NaCl. Thirty-eight participants attended 3 taste assessment sessions, each involving 24 triangle tests (2 blocks of 12 tests) containing 29 mM NaCl and 29 mM MSG, detection and recognition threshold were measured for MSG, monopotassium glutamate (MPG), and sweet (sucrose) tastes. There was no learning, or fatigue trend over n = 24 (P = 0.228), and n = 12 (P = 0.940) triangle tests across each testing session. Twenty-four triangle tests produced the most consistent categorization of tasters across sessions (68.4%). The test–retest correlation across each testing session was highest for n = 24 triangle tests (ICC = 0.50), in comparison to 12 (ICC = 0.37). Overall, conducting n = 24 compared with n = 12 triangle tests provided the optimal classification to determine an individual’s ability to discriminate l-glutamate from NaCl and thus their umami discrimination status, based on the number of tests assessed in this study.

Bitter taste receptors (hTAS2R) are expressed ectopically in various tissues, raising the possibility of a pharmacological exploitation. This seems of particular relevance in airways, since hTAS2Rs are involved in the protection of the aerial tissues from infections and in bronchodilation. The bis-guaianolide absinthin (1), one of the most bitter compounds known, targets the hTAS2R46 bitter receptor. Absinthin (1), an unstable compound, readily turns into anabsinthin (2) with substantial retention of the bitter properties, and this compound was used as a starting material to explore the chemical space around the bis-guaianolide bitter pharmacophore. Capitalizing on the chemoselective opening of the allylic lactone ring, the esters 3 and 4, and the nor-azide 6 were prepared and assayed on human bronchoepithelial (BEAS-2B) cells expressing hTAS2R46. Anti-inflammatory activity was evaluated by measuring the expression of MUC5AC, iNOS, and cytokines, as well as the production of superoxide anion, qualifying the methyl ester 3 as the best candidate for additional studies.

The aim of this study was to examine taste function in patients who reported improvement in their pain level after treatment to determine if pain reduction is associated with change in taste function in patients with burning mouth syndrome (BMS).This retrospective study of patients with BMS was conducted at a private oral medicine clinic.Thirty-nine patients with BMS (31 females and 8 males; mean age 56.1 ± 9.4 years) reported improvement in their pain in 1 to 22 months after the initial visit (mean 5.13 ± 4.18). The most commonly used medication was clonazepam 0.25 to 0.5 mg/day. Twenty-eight patients were treated with a combination of medications. "Salt" and "bitter" responses at the fungiform papillae were increased after treatment (P = .026 and P = .044, respectively). "Salt" responses at the circumvallate papillae also increased (P.001). Pain reduction was significant after treatment in the morning (P = .002) and in the evening (P.001).Treatment of BMS can significantly decrease pain symptoms, resulting in improvement in taste function. Pain reduction often requires a combination of medications.

Inborn genetic differences in chemosensory receptors can lead to differences in perception and preference for foods and beverages. These differences can drive market segmentation for food products as well as contribute to nutritional status. This knowledge may be essential in the development of foods and beverages because the sensory profiles may not be experienced in the same way across individuals. Rather, distinct consumer groups may exist with different underlying genetic variations. Identifying genetic factors associated with individual variability can help better meet consumer needs through an enhanced understanding of perception and preferences. This review provides an overview of taste and chemesthetic sensations and their receptors, highlighting recent advances linking genetic variations in chemosensory genes to perception, food preference and intake, and health. With growing interest in personalized foods, this information is useful for both food product developers and nutrition health professionals alike.

Numerous fatty acid receptors have proven to play critical roles in normal physiology. Interactions among these receptor types and their subsequent membrane trafficking has not been fully elucidated, due in part to the lack of efficient tools to track these cellular events. In this study, we fabricated the surface-enhanced Raman scattering (SERS)-based molecular sensors for detection of two putative fatty acid receptors, G protein-coupled receptor 120 (GPR120) and cluster of differentiation 36 (CD36), in a spatiotemporal manner in single cells. These SERS probes allowed multiplex detection of GPR120 and CD36, as well as a peak that represented the cell. This multiplexed sensing system enabled the real-time monitoring of fatty acid-induced receptor activation and dynamic distributions on the cell surface, as well as tracking of the receptors’ internalization processes on the addition of fatty acid. Increased SERS signals were seen in engineered HEK293 cells with higher fatty acid concentrations, while decreased responses were found in cell line TBDc1, suggesting that the endocytic process requires innate cellular components. SERS mapping results confirm that GPR120 is the primary receptor and may work synergistically with CD36 in sensing polyunsaturated fatty acids and promoting Ca 2+ mobilization, further activating the process of fatty acid uptake. The ability to detect receptors’ locations and monitor fatty acid-induced receptor redistribution demonstrates the specificity and potential of our multiplexed SERS imaging platform in the study of fatty acid–receptor interactions and might provide functional information for better understanding their roles in fat intake and development of fat-induced obesity.

Salt taste is one of the 5 basic taste qualities. Depending on the concentration, table salt is perceived either as appetitive or aversive, suggesting the contribution of several mechanisms to salt taste, distinguishable by their sensitivity to the epithelial sodium channel (ENaC) blocker amiloride. A taste-specific knockout of the α-subunit of the ENaC revealed the relevance of this polypeptide for low-salt transduction, whereas the response to other taste qualities remained normal. The fully functional ENaC is composed of α-, β-, and γ-subunits. In taste tissue, however, the precise constitution of the channel and the cell population responsible for detecting table salt remain uncertain. In order to examine the cells and subunits building the ENaC, we generated mice carrying modified alleles allowing the synthesis of green and red fluorescent proteins in cells expressing the α- and β-subunit, respectively. Fluorescence signals were detected in all types of taste papillae and in taste buds of the soft palate and naso-incisor duct. However, the lingual expression patterns of the reporters differed depending on tongue topography. Additionally, immunohistochemistry for the γ-subunit of the ENaC revealed a lack of overlap between all potential subunits. The data suggest that amiloride-sensitive recognition of table salt is unlikely to depend on the classical ENaCs formed by α-, β-, and γ-subunits and ask for a careful investigation of the channel composition.

Fungiform papillae are raised lingual structures which contain taste buds and thus play an important role in taste perception. These structures vary in number due to their relative sensitivity to a range of systemic and local factors which affect the dorsum of the tongue. Taste sensation can be measured using both chemical and electrical methods; however, the number of fungiform papillae has a direct effect on chemogustometric and electrogustometric values during evaluation. This review provides a general overview of fungiform papillae, their quantification methods and the various factors which may affect these structures. In addition, numerous methods of recording taste sensation and their clinical applications are highlighted.

Considering that nutrients are required in health and diseases, the detection and ingestion of food to meet the requirements is attributable to the sense of taste. Altered taste sensations lead to a decreased appetite, which is usually one of the frequent causes of malnutrition in patients with diseases. Ongoing taste research has identified a variety of drug pathways that cause changes in taste perceptions in cancer, increasing our understanding of taste disturbances attributable to aberrant mechanisms of taste sensation. The evidence discussed in this review, which addresses the implications of innate immune responses in the modulation of taste functions, focuses on the adverse effects on taste transmission from taste buds by immune modulators responsible for alterations in the perceived intensity of some taste modalities. Another factor, damage to taste progenitor cells that directly results in local effects on taste buds, must also be considered in relation to taste disturbances in patients with cancer. Recent discoveries discussed have provided new insights into the pathophysiology of taste dysfunctions associated with the specific treatments. SIGNIFICANCE STATEMENT The paradigm that taste signals transmitted to the brain are determined only by tastant-mediated activation via taste receptors has been challenged by the immune modification of taste transmission through drugs during the processing of gustatory information in taste buds. This article reports the findings in a model system (mouse taste buds) that explain the basis for the taste dysfunctions in patients with cancer that has long been observed but never understood.

Taste-signaling proteins, which are expressed throughout the digestive tract, are involved in regulating metabolism and immunity. This study aimed to determine if these genes are expressed and altered in jejunal tissues from patients with extreme obesity who received bariatric surgery. Reverse transcription polymerase chain reaction revealed that phospholipase C beta 2 and transient receptor potential channel M5 expression was downregulated in the jejunum of patients with a body mass index above 50, whereas gustducin expression remained unchanged. Our data suggest that taste-signaling dysregulation might contribute to obesity.

Sweet taste perception is mediated by a heterodimeric receptor formed by the assembly of the TAS1R2 and TAS1R3 subunits. TAS1R2 and TAS1R3 are class C G-protein-coupled receptors whose members share a common topology, including a large extracellular N-terminal domain (NTD) linked to a seven transmembrane domain (TMD) by a cysteine-rich domain. TAS1R2-NTD contains the primary binding site for sweet compounds, including natural sugars and high-potency sweeteners, whereas the TAS1R2-TMD has been shown to bind a limited number of sweet tasting compounds. To understand the molecular mechanisms governing receptor–ligand interactions, we overexpressed the human TAS1R2 (hTAS1R2) in a stable tetracycline-inducible HEK293S cell line and purified the detergent-solubilized receptor. Circular dichroism spectroscopic studies revealed that hTAS1R2 was properly folded with evidence of secondary structures. Using size exclusion chromatography coupled to light scattering, we found that the hTAS1R2 subunit is a dimer. Ligand binding properties were quantified by intrinsic tryptophan fluorescence. Due to technical limitations, natural sugars have not been tested. However, we showed that hTAS1R2 is capable of binding high potency sweeteners with Kd values that are in agreement with physiological detection. This study offers a new experimental strategy to identify new sweeteners or taste modulators that act on the hTAS1R2 and is a prerequisite for structural query and biophysical studies.

Taste is one of the most basic and important sensations that is able to monitor the food quality and avoid intake of potential danger materials. Whether as an inevitable symptom of aging or a complication of cancer treatment, taste loss so seriously affects the patient’s life quality. Taste bud organoids provide a great convenience for the research of taste functions and the underlying mechanisms due to their characteristics of availability, strong maneuverability, and high similarity to the in-vivo taste buds. This review gives a systemic and comprehensive introduction to the preparation and application of taste bud organoids towards chemical sensing mechanisms. For the first, the basic structure and function of taste buds in biomedicine will be brief introduced. Then, the currently available approaches for the preparation of taste bud organoids are summarized and discussed, which are mainly divided into two categories, i.e. stem/progenitor cell-derived approach and tissue-derived approach. For the next, different applications of taste bud organoids in biomedicine are outlined based on their central roles such as disease modeling, biological sensing, gene regulation, and signal transduction. Finally, the current challenges, future development trends and prospects of research in taste bud organoids are proposed and discussed.

Taste receptors, originally identified in taste buds, function as the periphery receptors for taste stimuli and play an important role in food choice. Cohort studies have revealed that single nucleotide polymorphisms of taste receptors such as T1R1, T1R2, T2R38 are associated with susceptibility to oral diseases like dental caries. Recent studies have demonstrated the wide expression of taste receptors in various tissues, including intestinal epithelia, respiratory tract, and gingiva, with an emerging role of participating in the interaction between mucosa surface and microorganisms via monitoring a wide range of metabolites. On the one hand, individuals with different oral microbiomes exhibited varied taste sensitivity, suggesting a potential impact of the oral microbiota composition on taste receptor function. On the other hand, animal studies and in vitro studies have uncovered that a variety of oral cells expressing taste receptors such as gingival solitary chemosensory cells, gingival epithelial cells (GECs), and gingival fibroblasts can detect bacterial signals through bitter taste receptors to trigger host innate immune responses, thus regulating oral microbial homeostasis. This review focuses on how taste receptors, particularly bitter and sweet taste receptors, mediate the oral microbiota-host interaction as well as impact the occurrence and development of oral diseases. Further studies delineating the role of taste receptors in mediating oral microbiota-host interaction will advance our knowledge in oral ecological homeostasis establishment, providing a novel paradigm and treatment target for the better management of dental infectious diseases.

As the most favoured animal companion of humans, dogs occupy a unique place in society. Understanding the senses of the dog can bring benefits to both the dogs themselves and their owners. In the case of bitter taste, research may provide useful information on sensitivity to, and acceptance of, diets containing bitter tasting materials. It may also help to protect dogs from the accidental ingestion of toxic substances, as in some instances bitter tasting additives are used as deterrents to ingestion. In this study we examined the receptive range of dog bitter taste receptors (Tas2rs). We found that orthologous dog and human receptors do not always share the same receptive ranges using in vitro assays. One bitter chemical often used as a deterrent, denatonium benzoate, is only moderately active against dTas2r4, and is almost completely inactive against other dog Tas2rs, including dTas2r10, a highly sensitive receptor in humans. We substituted amino acids to create chimeric dog-human versions of the Tas2r10 receptor and found the ECL2 region partly determined denatonium sensitivity. We further confirmed the reduced sensitivity of dogs to this compound in vivo. A concentration of 100μM (44.7ppm) denatonium benzoate was effective as a deterrent to dog ingestion in a two-bottle choice test indicating higher concentrations may increase efficacy for dogs. These data can inform the choice and concentration of bitter deterrents added to toxic substances to help reduce the occurrence of accidental dog poisonings.

Vitamins are known to generate bitterness, which may contribute to an off-taste or aftertaste for some nutritional supplements. This negative sensation can lead to a reduction in their consumption. Little is known about the bitter taste threshold and taste sensing system for the bitter taste detection of vitamins. To better understand the mechanisms involved in bitterness perception, we combined taste receptor functional assays and sensory analysis. In humans, bitter taste detection is mediated by 25 G-protein-coupled receptors belonging to the TAS2R family. First, we studied the bitterness of thirteen vitamins using a cellular-based functional taste receptor assay. We found four vitamins that can stimulate one or more TAS2Rs. For each positive molecule–receptor combination, we tested seven increasing concentrations to determine the half-maximal effective concentration (EC50) and the cellular bitter taste threshold. Second, we measured the bitter taste detection threshold for four vitamins that exhibit a strong bitter taste using a combination of ascending series and sensory difference tests. A combination of sensory and biological data can provide useful results that explain the perception of vitamin bitterness and its real contribution to the off-taste of nutritional supplements.

This review summarizes our understanding of ATP signaling in taste and describes new directions for research. ATP meets all requisite criteria to be considered a neurotransmitter: (1) presence in taste cells, as in all cells; (2) release upon appropriate taste stimulation; (3) binding to cognate purinergic receptors P2X2 and P2X3 on gustatory afferent neurons, and (4) after release, enzymatic degradation to adenosine and other nucleotides by the ectonucleotidase, NTPDase2, expressed on the Type I, glial-like cells in the taste bud. Importantly, double knockout of P2X2 and P2X3 or pharmacological inhibition of P2X3 abolishes transmission of all taste qualities. In Type II taste cells (those that respond to sweet, bitter, or umami stimuli), ATP is released non-vesicularly by a large conductance ion channel composed of CALHM1 and CALHM3, which form a so-called channel synapse at areas of contact with afferent taste nerve fibers. Although ATP release has been detected only from Type II cells, it is also required for the transmission of salty and sour stimuli, which are mediated primarily by the Type III taste cells. The source of the ATP required for Type III cell signaling to afferent fibers is still unclear and is a focus for future experiments. The ionotropic purinergic receptor, P2X3, is widely expressed on many sensory afferents and has been a therapeutic target for treating chronic cough and pain. However, its requirement for taste signaling has complicated efforts at treatment since patients given P2X3 antagonists report substantial disturbances of taste and become non-compliant.

Many reports detail taste dysfunction in humans and animals with obesity. For example, mice consuming an obesogenic diet for a short period have fewer taste buds than their lean littermates. Further, rats with diet-induced obesity (DIO) show blunted electrophysiological responses to taste in the brainstem. Here, we studied the effects of high energy diet (HED)-induced peripheral taste damage in rats, and whether this deficiency could be reversed by returning to a regular chow diet. Separate groups of rats consumed a standard chow diet (Chow), a HED for 10 weeks followed by a return to chow (HED/chow), or a HED for 10 weeks followed by a restricted HED that was isocaloric with consumption by the HED/chow group (HED/isocal). Fungiform taste papilla (FP) and circumvallate taste bud abundance were quantified several months after HED groups switched diets. Results showed that both HED/chow and HED/isocal rats had significantly fewer FP and lower CV taste bud abundance than control rats fed only chow. Neutrophil infiltration into taste tissues was also quantified, but did not vary with treatment on this timeline. Finally, the number of cells undergoing programmed cell death, measured with caspase-3 staining, inversely correlated with taste bud counts, suggesting taste buds may be lost to apoptosis as a potential mechanism for the taste dysfunction observed in obesity. Collectively, these data show that DIO has lasting deleterious effects on the peripheral taste system, despite a change from a HED to a healthy diet, underscoring the idea that obesity rather than diet predicts damage to the taste system.

The umami taste receptor is a heterodimer composed of two members of the T1R taste receptor family: T1R1 (taste receptor type 1 member 1) and T1R3 (taste receptor type 1 member 3). Taste receptor T1R1-T1R3 can be activated, or modulated, by binding to several natural ligands, such as L-glutamate, inosine-5'-monophosphate (IMP), and guanosine-5'-monophosphate (GMP). Because no structure of the umami taste receptor has been solved until now, in silico techniques, such as homology modelling, molecular docking, and molecular dynamics (MD) simulations, are used to generate a 3D structure model of this receptor and to understand its molecular mechanisms. The purpose of this chapter is to highlight how computational methods can provide a better deciphering of the mechanisms of action of umami ligands in activating the umami taste receptors leading to advancements in the taste research field.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for the coronavirus disease 2019 (COVID-19), has imposed unprecedented morbidity and mortality worldwide. As of June 2021, globally over 163 million individuals are infected and nearly 3.4 million individuals have died. Emerging concerns include complaints of persistent symptoms for extended periods in recovered individuals. Cellular damage due to disease and/or treatment, prolonged viral shedding, chronic immune inflammatory response, and pro-coagulant state induced by SARS-CoV-2 infection are suggested mechanisms contributing to the symptom sequelae (Estiri et al., 2021; Tran et al., 2021).

The molecules that elicit taste sensation are perceived by interacting with the taste receptors located in the taste buds. Enzymes involved in the detoxification processes are found in saliva as well as in type II cells, where taste receptors, including bitter taste receptors, are located. These enzymes are known to interact with a large panel of molecules. To explore a possible link between these enzymes and bitter taste perception, we demonstrate that salivary glutathione transferases (GSTA1 and GSTP1) can metabolize bitter molecules. To support these abilities, we solve three X-ray structures of these enzymes in complexes with isothiocyanates. Salivary GSTA1 and GSTP1 are expressed in a large panel of subjects. Additionally, GSTA1 levels in the saliva of people suffering from taste disorders are significantly lower than those in the saliva of the control group.

Sour, the taste of acids, provides important sensory information to prevent the ingestion of unripe, spoiled, or fermented foods. In mammals, acids elicit disgust and pain by simultaneously activating taste and somatosensory neurons innervating the oral cavity. Early researchers detected electrical activity in taste nerves upon presenting acids to the tongue, establishing this as the bona fide sour taste. Recent studies have made significant contributions to our understanding of the mechanisms underlying acid sensing in the taste receptor cells at the periphery and the neural circuitry that convey this information to the brain. In this chapter, we discuss the characterization of sour taste receptor cells, the twists and turns eventually leading to the identification of Otopetrin1 (OTOP1) as the sour taste receptor, the pathway of sour taste signaling from the tongue to the brainstem, and other roles sour taste receptor cells play in the taste bud.

It has recently been shown that taste receptors, in addition to being present in the oral cavity, exist in various extra-oral organs and tissues such as the thyroid, lungs, skin, stomach, intestines, and pancreas. Although their physiological function is not yet fully understood, it appears that they can help regulate the body's homeostasis and provide an additional defense function against pathogens. Since the vast majority of drugs are bitter, the greatest pharmacological interest is in the bitter taste receptors. In this review, we describe how bitter taste 2 receptors (TAS2Rs) induce bronchodilation and mucociliary clearance in the airways, muscle relaxation in various tissues, inhibition of thyroid stimulating hormone (TSH) in thyrocytes, and release of glucagon-like peptide-1 (GLP-1) and ghrelin in the digestive system. In fact, substances such as dextromethorphan, chloroquine, methimazole and probably glimepiride, being agonists of TAS2Rs, lead to these effects. TAS2Rs and taste 1 receptors (TAS1R2/3) are G protein-coupled receptors (GPCR). TAS1R2/3 are responsible for sweet taste perception and may induce GLP-1 release and insulin secretion. Umami taste receptors, belonging to the same superfamily of receptors, perform a similar function with regard to insulin. The sour and salty taste receptors work in a similar way, both being channel receptors sensitive to amiloride. Finally, gene-protein coupled receptor 40 (GPR40) and GPR120 for fatty taste perception are also protein-coupled receptors and may induce GLP-1 secretion and insulin release, similar to those of other receptors belonging to the same superfamily.

Taste buds consist of specialized epithelial cells which detect particular tastants and synapse onto the afferent taste nerve innervating the endorgan. The nature of the neurotransmitter released by taste cells onto the nerve fiber was enigmatic early in this century although neurotransmitters for other sensory receptor cell types, e.g. hair cells, photoreceptors, was known for at least a decade. A 1999 paper by Burnstock and co-workers (Bo et al., 1999) showing the presence of P2X receptors on the afferent nerves served as a springboard for research that ultimately led to the discovery of ATP as the crucial neurotransmitter in the taste system (Finger et al., 2005). Subsequent work showed that a subpopulation of taste cells utilize a unique release channel, CALHM1/3, to release ATP in a voltage-dependent manner. Despite these advances, several aspects of purinergic transmission in this system remain to be elucidated.

(Background) We investigated the effect of dietary supplementation with monosodium glutamate (MSG) on chemotherapy-induced downregulation of the T1R3 taste receptor subunit expression in the tongue of patients with advanced head and neck cancer. (Methods) Patients undergoing two rounds of chemoradiotherapy were randomly allocated to a control or intervention group (dietary supplementation with MSG at 2.7 g/day during the second round of chemotherapy). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative polymerase chain reaction analysis. Dysgeusia was assessed with a visual analog scale and daily energy intake was evaluated. (Results) T1R3 expression levels in the tongue, taste sensitivity, and daily energy intake were significantly reduced after the first round of chemotherapy compared with before treatment. Furthermore, these parameters significantly decreased after the second round of chemotherapy, but the extent of decrease was significantly attenuated in the MSG group compared with the control group. (Conclusions) MSG supplementation suppresses chemotherapy-induced dysgeusia, possibly due to the inhibition of the T1R3-containing taste receptor downregulation in the tongue, thereby increasing energy intake in patients with advanced head and neck cancer.