Bitter Taste Sensitivity Research Articles

Rare haplotypes of the gene TAS2R38 confer bitter taste sensitivity in humans.

BackgroundThe TAS2R38 gene is widely responsible for the well-known bimodal response to a family of bitter chemicals which includes 6-n-propylthiouracial (PROP). There are two common haplotypes of this gene, the recessive AVI and the dominant PAV, both of which are well studied. Conversely, the role of rare TAS2R38 haplotypes on bitter taste sensitivity has been notoriously difficult to study due to small sample sizes. Here we present PROP sensitivity data of 97 individuals that have been observed to carry rare haplotypes (AAV, AAI, PAI, PVI) of the TAS2R38 gene.ResultsParticipants rated their bitter taste perception to a PROP filter disc then provided a buccal DNA sample from which the TAS2R38 gene was sequenced and analyzed. We found the prevalence of the PAV haplotype to be 42.3 %, AVI 53.1 %, AAV 2.5 %, AAI 1.2 %, PAI 0.8 % and PVI 0.1 %. We found that the AAI, AAV, and PAI haplotypes present intermediate taste sensitivity.ConclusionsThese data are further evidence that bitter taste sensitivity to PROP exists as a broad range, and not exclusively as nontasters, medium tasters, and supertasters.

Variability in Human Bitter Taste Sensitivity to Chemically Diverse Compounds Can Be Accounted for by Differential TAS2R Activation.

The human population displays high variation in taste perception. Differences in individual taste sensitivity may also impact on nutrient intake and overall appetite. A well-characterized example is the variable perception of bitter compounds such as 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC), which can be accounted for at the molecular level by polymorphic variants in the specific type 2 taste receptor (TAS2R38). This phenotypic variation has been associated with influencing dietary preference and other behaviors, although the generalization of PROP/PTC taster status as a predictor of sensitivity to other tastes is controversial. Here, we proposed that the taste sensitivities of different bitter compounds would be correlated only when they activate the same bitter taste receptor. Thirty-four volunteers were exposed to 8 bitter compounds that were selected based on their potential to activate overlapping and distinct repertoires of TAS2Rs. Taste intensity ratings were evaluated using the general Labeled Magnitude Scale. Our data demonstrate a strong interaction between the intensity for bitter substances when they activate common TAS2Rs. Consequently, PROP/PTC sensitivity was not a reliable predictor of general bitter sensitivity. In addition, our findings provide a novel framework to predict taste sensitivity based on their specific T2R activation profile.

Phenylthiocarbamide taste sensitivity is associated with sinonasal symptoms in healthy adults.

The bitter taste receptor T2R38, expressed in the tongue and nasal epithelium, has been shown to trigger sinonasal innate immunity contributing to the prevention of gram-negative upper airway bacterial infections. Common polymorphisms of the T2R38 gene, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been linked to differences in sinonasal innate immune response, with specific genotypes significantly more common in medically recalcitrant chronic rhinosinusitis patients. The purpose of this study was to examine this association between T2R38 function and sinonasal infection or symptoms in a healthy population. A survey of the frequency of sinus infections, as well as other nasal symptoms such as colds, allergies, and overall nasal quality of life (nQOL), was administered to healthy adult participants. nQOL was measured using a 0 to 3 scale of worsening symptoms. A PTC compound taste strip was administered with T2R38 taste sensitivity classified as extremely, somewhat, or not sensitive. Among 217 participants (55% female, 70% Caucasian, 42% age 21 to 25 years), 30% did not detect bitterness (nontasters), 34% were moderate tasters, and 36% were "supertasters," experiencing a strong, unpalatable bitterness. Supertasters were associated with less frequent sinus infections (p = 0.04), and PTC sensitivity was predictive of nasal symptoms: Supertasters had the best nQOL scores, followed by moderate tasters and nontasters (means: 0.65, 0.81, 1.00, respectively; p = 0.014 for trend). There were no significant associations with other variables. This study provides evidence that T2R38 functionality in the tongue correlates with nasal symptoms in healthy individuals.

Independent, Reciprocal Neuromodulatory Control of Sweet and Bitter Taste Sensitivity during Starvation in Drosophila

An organism's behavioral decisions often depend upon the relative strength of appetitive and aversive sensory stimuli, the relative sensitivity to which can be modified by internal states like hunger. However, whether sensitivity to such opposing influences is modulated in a unidirectional or bidirectional manner is not clear. Starved flies exhibit increased sugar and decreased bitter sensitivity. It is widely believed that only sugar sensitivity changes, and that this masks bitter sensitivity. Here we use gene- and circuit-level manipulations to show that sweet and bitter sensitivity are independently and reciprocally regulated by starvation in Drosophila. We identify orthogonal neuromodulatory cascades that oppositely control peripheral taste sensitivity for each modality. Moreover, these pathways are recruited at increasing hunger levels, such that low-risk changes (higher sugar sensitivity) precede high-risk changes (lower sensitivity to potentially toxic resources). In this way, state-intensity-dependent, reciprocal regulation of appetitive and aversive peripheral gustatory sensitivity permits flexible, adaptive feeding decisions.

Effects of sucrose detection threshold and weight status on intake of fruit and vegetables in children

Past research on the relationship between taste sensitivity and fruit and vegetable (FV) intake in children has focused on sensitivity to bitter taste. The effects of sensitivity to sweet taste on intake of FV have never been investigated. Furthermore, the effects of children's weight on intake of FV are inconclusive. This study measured the effects of Sucrose Detection Threshold (SDT) and weight status on intake of FV in children. The participants of this study were 99 children between 5–9 years old. Parents reported their own and their children's 24 hour intake of FV and completed a measure of children's sensory sensitivity. Children completed the triangle test with suprathreshold concentrations of sucrose ranging between 0.2% and 1.6%, in 0.2% increments. Two MANCOVAs showed that, controlling for parental intake and children's sensory sensitivity, there was a main effect of SDT on intake of fruit (p < 0.05), which was exclusive to non-astringent fruit (p < 0.05), and cruciferous vegetables (p < 0.01). Weight status had no effect on intake of FV. Mechanisms behind the effects of SDT are discussed in the context of past research on bitter taste sensitivity.

Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa

Bitter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. To better understand the genetic architecture and patterns of phenotypic variability of bitter taste perception, we sequenced a 996 bp region, encompassing the coding exon of TAS2R16, a bitter taste receptor gene, in 595 individuals from 74 African populations and in 94 non-Africans from 11 populations. We also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from Central and East Africa. In addition, we characterized TAS2R16 mutants in vitro to investigate the effects of polymorphic loci identified at this locus on receptor function. Here, we report striking signatures of positive selection, including significant Fay and Wu's H statistics predominantly in East Africa, indicating strong local adaptation and greater genetic structure among African populations than expected under neutrality. Furthermore, we observed a "star-like" phylogeny for haplotypes with the derived allele at polymorphic site 516 associated with increased bitter taste perception that is consistent with a model of selection for "high-sensitivity" variation. In contrast, haplotypes carrying the "low-sensitivity" ancestral allele at site 516 showed evidence of strong purifying selection. We also demonstrated, for the first time, the functional effect of nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse Africans and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression in vitro, suggesting that one main polymorphism at TAS2R16 influences salicin recognition. Additionally, we detected geographic differences in levels of bitter taste perception in Africa not previously reported and infer an East African origin for high salicin sensitivity in human populations.

Change of Taste Sensitivity of Clove Cigarette Smokers in Medan

Tongue has taste buds that contain taste receptor which affected by many factors, including smoking habit. Objective: To analyze the differences of sweet and bitter taste sensitivity in the pedicab driver clove cigarette smokers compared to non-smokers in Medan Padang Bulan. Methods: This study was conducted by placing the sweet taste strips and bitter taste strips on four taste receptors of the tongue, with increasing solution concentration in 74 subjects. This was a cross sectional study on pedicab driver population in Medan Padang Bulan. Results: There were differences between clove cigarette smokers and non-smokers on sweet taste examination (p<0.005). There was a difference between clove cigarette smokers and non-smokers on examination bitter taste receptors (p<0.005). On the clove cigarette smokers, there was no significant difference between sweet taste and bitter taste on the receptors itself. Conclusion: Non-smokers are more sensitive to sweet taste than the clove cigarette smokers. Bitter taste sensitivity is greater in cigarettes smokers than in non-smokers. Taste receptors on all location of the tongue could taste sweet and bitter substances, but a certain location of taste receptors were more sensitive compared to others.

In Pursuit of Taste Phenotypes

Notable progress has been made relating individual differences in bitter taste sensitivity to specific alleles and TAS2R receptors, but psychophysical evidence of reliable phenotypes for other tastes has been more elusive. In this issue, Wise and Breslin report a study of individual differences in threshold sensitivity to sour and salty taste, which, though failing to find clear phenotypes, exemplifies the type of approach and analysis necessary to disentangle sources of variance inherent in the psychophysical measures applied from those attributable to true differences in sensitivity. Methodological and theoretical lessons that can be taken from this work are discussed in the context of the early and dramatic evidence of chemosensory phenotypes that belied the complexity of taste receptor genetics and focused attention solely on peripheral determinants of sensitivity.

Variation in the Gene TAS2R13 is Associated with Differences in Alcohol Consumption in Patients with Head and Neck Cancer

Variation in responsiveness to bitter-tasting compounds has been associated with differences in alcohol consumption. One strong genetic determinant of variation in bitter taste sensitivity is alleles of the TAS2R gene family, which encode chemosensory receptors sensitive to a diverse array of natural and synthetic compounds. Members of the TAS2R family, when expressed in the gustatory system, function as bitter taste receptors. To better understand the relationship between TAS2R function and alcohol consumption, we asked if TAS2R variants are associated with measures of alcohol consumption in a head and neck cancer patient cohort. Factors associated with increased alcohol intake are of strong interest to those concerned with decreasing the incidence of cancers of oral and pharyngeal structures. We found a single nucleotide polymorphism (SNP) located within the TAS2R13 gene (rs1015443 [C1040T, Ser259Asn]), which showed a significant association with measures of alcohol consumption assessed via the Alcohol Use Disorders Identification Test (AUDIT). Analyses with other SNPs in close proximity to rs1015443 suggest that this locus is principally responsible for the association. Thus, our results provide additional support to the emerging hypothesis that genetic variation in bitter taste receptors can impact upon alcohol consumption.

Functional diversity of bitter taste receptor TAS2R16 in primates

In mammals, bitter taste is mediated by TAS2R genes, which belong to the large family of seven transmembrane G protein-coupled receptors. Because TAS2Rs are directly involved in the interaction between mammals and their dietary sources, it is likely that these genes evolved to reflect species-specific diets during mammalian evolution. Here, we investigated the sensitivities of TAS2R16s of various primates by using a cultured cell expression system, and found that the sensitivity of each primate species varied according to the ligand. Especially, the sensitivity of TAS2R16 of Japanese macaques to salicin was much lower than that of human TAS2R16, which was supported by behavioural tests. These results suggest the possibility that bitter-taste sensitivities evolved independently by replacing specific amino acid residues of TAS2Rs in different primate species to adapt to food items they use.

Offering “Dip” Promotes Intake of a Moderately-Liked Raw Vegetable among Preschoolers with Genetic Sensitivity to Bitterness

BackgroundEvidence-based strategies for promoting vegetable consumption among children are limited. ObjectiveTo determine the effects of providing a palatable “dip” along with repeated exposure to a raw vegetable on preschoolers' liking and intake. ParticipantsOne hundred fifty-two predominately Hispanic preschool-aged children studied in Head Start classrooms in 2008. DesignA between-subjects, quasiexperimental design was used. A moderately-liked raw vegetable (broccoli) was offered twice weekly at afternoon snacks for 7 weeks. Classrooms were randomized to receive broccoli in one of four conditions differing in the provision of dip. Bitter taste sensitivity was assessed using 6-n-propylthiouracil. InterventionBroccoli was provided in four conditions: with regular salad dressing as a dip, with a light (reduced energy/fat) version of the dressing as a dip, mixed with the regular dressing as a sauce, or plain (without dressing). Main outcome measuresMean broccoli intake during 7 weeks of exposure and broccoli liking following exposure. Statistical analysesDescriptive statistics were generated. Multilevel models for repeated measures tested effects of condition and bitter sensitivity on mean broccoli intake during exposure and on pre- and post-exposure liking while adjusting for classroom effects and potential covariates. ResultsThe majority of Hispanic preschoolers (70%) showed sensitivity to the bitter taste of 6-n-propylthiouracil. Children's broccoli liking increased following exposure but did not vary by dip condition or bitter sensitivity. Bitter-sensitive children, however, ate 80% more broccoli with dressing than when served plain (P<0.001); effects did vary based on whether regular or light dressing was provided as a dip or sauce. Dip did not promote broccoli intake among bitter-insensitive children. ConclusionsProviding dip—regular, light, or as a sauce—increased raw broccoli intake among bitter-sensitive Hispanic preschoolers. Findings suggest that offering low-fat dips can promote vegetable intake among some children who are sensitive to bitter tastes.

Evolution of Functionally Diverse Alleles Associated with PTC Bitter Taste Sensitivity in Africa

Although human bitter taste perception is hypothesized to be a dietary adaptation, little is known about genetic signatures of selection and patterns of bitter taste perception variability in ethnically diverse populations with different diets, particularly from Africa. To better understand the genetic basis and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from 57 populations in West Central and East Africa with diverse subsistence patterns, as well as in a comparative sample of 132 non-Africans. We also examined the association between genetic variability at this locus and threshold levels of phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations to determine how variation influences bitter taste perception. Here, we report striking patterns of variation at TAS2R38, including a significant excess of novel rare nonsynonymous polymorphisms that recently arose only in Africa, high frequencies of haplotypes in Africa associated with intermediate bitter taste sensitivity, a remarkably similar frequency of common haplotypes across genetically and culturally distinct Africans, and an ancient coalescence time of common variation in global populations. Additionally, several of the rare nonsynonymous substitutions significantly modified levels of PTC bitter taste sensitivity in diverse Africans. While ancient balancing selection likely maintained common haplotype variation across global populations, we suggest that recent selection pressures may have also resulted in the unusually high level of rare nonsynonymous variants in Africa, implying a complex model of selection at the TAS2R38 locus in African populations. Furthermore, the distribution of common haplotypes in Africa is not correlated with diet, raising the possibility that common variation may be under selection due to their role in nondietary biological processes. In addition, our data indicate that novel rare mutations contribute to the phenotypic variance of PTC sensitivity, illustrating the influence of rare variation on a common trait, as well as the relatively recent evolution of functionally diverse alleles at this locus.

Bitter taste induces nausea

Summary Nausea is the most characteristic negative experience that typically accompanies toxin-induced illness. Because most plant-derived toxins taste bitter, there is a rational link between bitter tasting compounds in the mouth and nausea that often results from their ingestion. It is surprising then that there are no experimental data demonstrating this connection. There are, however, data consistent with this notion. For example, people who are the most sensitive to bitter stimuli are more prone to motion sickness [1], and bitter taste sensitivity and pregnancy associated nausea are positively related, a response postulated to protect the fetus from poisoning [2]. Moreover, we know that bitter taste slows gastric emptying, a correlate of nausea [3]. Bitter taste is strongly sensed by the glossopharyngeal and vagus nerves [4], which innervate the posterior oral cavity and the gastrointestinal tract, respectively. The two projection fields of these sensory nerves are immediately adjacent within the nucleus of the solitary tract as well as in other brain relays [5], thus establishing a neuro-anatomical substrate for taste inputs to influence gastrointestinal states. Here, we report the first direct demonstration that bitter taste stimulation, but not sweet, salty, or umami taste, induces nausea, showing that the body not only detects potential toxins but anticipates their ingestion by inducing a prophylactic aversive state.

The number of taste buds is related to bitter taste sensitivity in layer and broiler chickens

The relationship between taste sensitivity and the number of taste buds using a bitter tastant, quinine hydrochloride, was investigated in White Leghorn, Rhode Island Red, and broiler chickens. The White Leghorn and Rhode Island Red strains were able to perceive 2.0 mmol/L quinine hydrochloride, but the taste sensitivity of Rhode Island Red chickens was higher than that of White Leghorn chickens. Broiler chickens perceived 0.5 mmol/L quinine hydrochloride. The number of taste buds in the White Leghorn strain was the lowest, then the Rhode Island Red strain, with the number of taste buds highest in the broiler chickens. The number of taste buds was well correlated with bitter taste sensitivity. Therefore, we suggest that the number of taste buds is a vital factor in the perception of bitter taste and may be useful in selecting appropriate feeds for chickens.

The gourmet ape: evolution and human food preferences

This review explores the relation between evolution, ecology, and culture in determining human food preferences. The basic physiology and morphology of Homo sapiens sets boundaries to our eating habits, but within these boundaries human food preferences are remarkably varied, both within and between populations. This does not mean that variation is entirely cultural or learned, because genes and culture may coevolve to determine variation in dietary habits. This coevolution has been well elucidated in some cases, such as lactose tolerance (lactase persistence) in adults, but is less well understood in others, such as in favism in the Mediterranean and other regions. Genetic variation in bitter taste sensitivity has been well documented, and it affects food preferences (eg, avoidance of cruciferous vegetables). The selective advantage of this variation is not clear. In African populations, there is an association between insensitivity to bitter taste and the prevalence of malaria, which suggests that insensitivity may have been selected for in regions in which eating bitter plants would confer some protection against malaria. Another, more general, hypothesis is that variation in bitter taste sensitivity has coevolved with the use of spices in cooking, which, in turn, is thought to be a cultural tradition that reduces the dangers of microbial contamination of food. Our evolutionary heritage of food preferences and eating habits leaves us mismatched with the food environments we have created, which leads to problems such as obesity and type 2 diabetes.

Lack of Relation Between Bitter Taste Receptor TAS2R38 and BMI in Adults

TO THE EDITOR: Recently, Tepper et al. in their article titled “Variation in the bitter-taste receptor gene TAS2R38, and adiposity in a genetically isolated population in Southern Italy” speculated whether polymorphisms in the bitter-taste receptor gene TAS2R38 are associated with adiposity. The authors concluded that BMI does not vary with genetically determined taster status although a statistically significant positive association was observed in men (1). Because the power of the study was low, we analyzed the association between TAS2R38 haplotypes and BMI in a larger study population to test whether the findings can be replicated, in particular for men. Present study population included 1,252 individuals with complete data aged 20–64 years participating in the European Community Respiratory Health Survey in 1990–1992 from the German study centre Erfurt. Study design and population sampling are described in detail elsewhere (2). Anthropometric measurements were performed at the study centre at the time of lung function testing. BMI was calculated as weight (kg)/height (m2). Information about smoking and education were taken from an interviewer-administered questionnaire. Blood samples were collected and DNA was extracted for genotyping. Genotyping of single-nucleotide polymorphisms (SNPs) was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry according to manufacturers' instructions (Mass Array; Sequenom, San Diego, CA). Haplotypes were reconstructed based on the three SNPs A49P (rs713598), V262A (rs1726866), and I296V (rs10246939) in the gene receptor TAS2R38. As demonstrated previously, PAV (homozygote and heterozygote) and AVI (homozygote) haplotypes refer to taster and nontaster status, respectively. Other variants are rare and are considered as being associated with intermediate bitter taste sensitivity (3,4). Allele frequencies in % were for rs713598 C/G: 39/61, for rs1726866 C/T: 42/58, and for rs10246939 G/A (C/T): 42/58. We conducted the same statistical analyses as Tepper et al. Analysis of covariance was applied to analyze differences in BMI by TAS2R38 haplotypes with adjustment for age. Multiple regression analysis was used to model BMI using TAS2R38 haplotype as a predictor adjusting for age, education, and current smoking. TAS2R38 haplotype frequencies in our study population are shown in Table 1. The prevalence of nontasters (AVI/AVI) was 33.1% in the whole study population and thus similar to the frequencies reported by Tepper et al. (28.3%) (ref. 1). Homozygote tasters (PAV/PAV) occurred less frequently with 14.5% in our study population compared to the study by Tepper et al. (with 22.5%). The major haplotype was the PAV/AVI haplotype (44.8%), which was grouped with other rare haplotype combinations accounting altogether for 52.5%. This table also shows that BMI did not differ between the three groups of TAS2R38 haplotypes neither for men (P = 0.338) nor for women (P = 0.797). According to the study by Tepper et al., we further performed a regression analysis to estimate the predictive effect of TAS2R38 haplotypes on BMI, stratified for sex (Table 2). All parameter estimates were adjusted for age, education, and smoking. Similar to the findings from Tepper et al., age had a strong positive influence on BMI in men and women. However, TAS2R38 haplotypes were not statistically significantly related to BMI, neither in men nor in women. The percent of variance explained by the model for men and women was R2 = 0.10 and R2 = 0.18, respectively. Additionally, we performed a stepwise multiple regression analysis with similar results. Even though our study was based on a larger study population than the one by Tepper et al., and applying the same statistical methods, we did not observe any relationship between this genetically determined bitter taste polymorphism and BMI, in either the entire cohort or in sex-stratified subgroups. Therefore, we conclude that there is no evidence that TAS2R38 haplotypes are associated with BMI in adult subjects. The authors declared no conflict of interest.

ＰＲＯＰ味覚感受性と苦味のある食品の嗜好との関係

The relationship between the bitter food preference and taste sensitivity to PROP (6-n-propylthiouracil) was examined in 108 university students. A taste test indicated that the preference for a straight coffee solution and caffeine fell with higher taste sensitivity to PROP; however, the preference for coffee with added milk and sugar, and for powdered tea (maccha) was not correlated with the taste sensitivity to PROP. The answers to a questionnaire showed that the preference for coffee and beer was not correlated with the taste sensitivity to PROP. These results suggest that the taste sensitivity to PROP may be related to bitter food preferences, but that the correlation may not be strong.

Variation in Nicotine Consumption in Inbred Mice Is Not Linked to Orosensory Ability

Genetic studies of nicotine addiction in mice have utilized the oral self-administration model. However, it is unclear if strain differences in nicotine consumption are influenced by variation in bitter taste sensitivity. We measured both nicotine consumption and nicotine brief-access licking behavior in several commonly used inbred strains of mice that were previously shown to differ in nicotine consumption. A/J (A), C57BL/6J (B6), and DBA/2J (D2) mice were given a 2-bottle choice test with a single concentration of nicotine (75 microg/ml; nicotine vs. water). Mice of these strains were also tested with a range of nicotine concentrations (5-400 microg/ml) using a brief-access test, which measures orosensory response and minimizes postingestive effects. Although B6 mice consumed more 75-microg/ml nicotine than A or D2 mice in the 2-bottle test, these strains did not differ in level of aversion to nicotine when tested with the brief-access procedure. Strain differences in orosensory response to nicotine were not found; yet, differences emerged during the 2-bottle tests. This study provides evidence that variation in intake level of nicotine is likely not due to differences in taste or trigeminal sensitivity but likely due to postingestive factors.

Are Dietary Preferences Linked To Genes?

When many choices are available, humans chose foods that ‘taste good’. The concept of good taste for most people encompasses both flavor and texture of food. Although we acknowledge the universality of the goodness (sweet) or badness (bitter) of basic taste qualities, we also find that people differ, sometimes extremely so, in their ability to perceive these qualities. There is great variability in dietary habits both within and between various cultures. The interindividual differences in the quantity and quality of foods we chose to consume appear to be partially genetic and partially acquired or imposed by social or economic influences [1]. The contribution of genetics to dietary behaviors has been derived from family studies. The heritability estimates for macronutrients, including total energy intake range anywhere from 10 to 70% [2–6]. The different analytical and dietary assessment methods may explain the wide range of these estimates. These studies support the role of genetics in food consumption, but also point to the complexity of human dietary behaviors. With the exception of monogenetic conditions such as with leptin deficiency, no single gene is likely to have a great impact on food selection and intake. It is most likely that multiple physiological pathways are involved in these processes with those involved in taste perception being one of the actively studied subjects in the context of dietary behavior. Five modalities of taste can be detected by most mammals: sweet, salt, sour, bitter and umami [7–9]. Increasing evidence supports the addition of fat taste to the list of classical taste modalities. The exact role of each taste on dietary behavior is unclear, however, it is generally thought that sweet, salt and umami ensure nutrient acquisition while bitter and sour elicit food rejection. In the case of the bitter taste sensitivity, this may have served in ancestral times as a defense against ingestion of toxic compounds in foods. However, for modern humans, the role of bitter taste perception for the avoidance of noxious food is less important, and it is thought that individual differences to bitter taste sensitivity may influence health outcomes through its effect on dietary behaviors. In this regard, sensitivity to phenylthiocarbamide (PTC) and its chemical relative, 6-n-propylthiouracil (PROP) has provided some insight into the role of bitter taste perception on preferences and consumption of bitter foods. The haplotypes of the taste receptor, type 2, member 38 (TAS2R38) gene accounts for most of the variability of PTC sensitivity. There have been a few studies that support the role of this gene with preferences to vegetables and alcohol consumption. However, the current evidence has yet to support a link between genetic variability at this taste candidate gene, habitual consumption of certain foods and health related outcomes. This is expected when considering the complexity of the large number of taste related genes as well as other pathways that modulate eating habits, such as those involved in the central control of energy intake including neuropeptides and monoamine systems (reviewed in [10]) and the more recent developments regarding fat intake preferences [11,12].

Specific Alleles of Bitter Receptor Genes Influence Human Sensitivity to the Bitterness of Aloin and Saccharin

Variation in human taste is a well-known phenomenon. However, little is known about the molecular basis for it. Bitter taste in humans is believed to be mediated by a family of 25 G protein-coupled receptors (hT2Rs, or TAS2Rs). Despite recent progress in the functional expression of hT2Rs in vitro, up until now, hT2R38, a receptor for phenylthiocarbamide (PTC), was the only gene directly linked to variations in human bitter taste. Here we report that polymorphism in two hT2R genes results in different receptor activities and different taste sensitivities to three bitter molecules. The hT2R43 gene allele, which encodes a protein with tryptophan in position 35, makes people very sensitive to the bitterness of the natural plant compounds aloin and aristolochic acid. People who do not possess this allele do not taste these compounds at low concentrations. The same hT2R43 gene allele makes people more sensitive to the bitterness of an artificial sweetener, saccharin. In addition, a closely related gene's (hT2R44's) allele also makes people more sensitive to the bitterness of saccharin. We also demonstrated that some people do not possess certain hT2R genes, contributing to taste variation between individuals. Our findings thus reveal new examples of variations in human taste and provide a molecular basis for them.