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In healthy humans, taste sensitivity varies widely, influencing food selection and nutritional status. Chemosensory loss has been associated with numerous pathological disorders and pharmacological interventions. Reliable psychophysical methods are crucial for analyzing the taste function during routine clinical assessment. However, in the daily clinical routine, they are often considered too time-consuming. We used a supervised learning (SL) regression method to analyze with high precision the overall taste statuses of healthy controls (HCs) and patients with chemosensory loss, and to characterize the combination of responses that would best predict the overall taste statuses of the subjects in the two groups. The random forest regressor model allowed us to achieve our objective. The analysis of the order of importance of each parameter and their impact on the prediction of the overall taste statuses of the subjects in the two groups showed that salty (low-concentration) and sour (high-concentration) stimuli specifically characterized healthy subjects, while bitter (high-concentration) and astringent (high-concentration) stimuli identified patients with chemosensory loss. Although the present results require confirmation in studies with larger samples, the identification of such distinctions should be of interest to the health system because they may justify the use of specific stimuli during the routine clinical assessments of taste function and thereby reduce time and cost commitments.

Smell strongly contributes to food choice and its hedonistic evaluation. A reduction or loss of smell has been related to malnutrition problems, resulting in excessive weight loss or gain. Voltage-gated potassium channels Kv1.3 are widely expressed in the olfactory bulb, and contribute mainly to the value of the resting membrane potential and to the frequency of action potentials. Mutations in the Kv1.3 gene are associated with alterations in glycemic homeostasis and olfactory sensitivity. We evaluated the olfactory performance in 102 healthy subjects and its association with BMI and polymorphism in the human Kv1.3 gene. Olfactory performance, based on the olfactory threshold, discrimination and identification scores and their summed score (TDI), was measured using the “Sniffin’ Sticks” test. Subjects were genotyped for the rs2821557 polymorphism of the Kv1.3 gene, whose major allele T was associated with a super-smeller phenotype, lower plasma glucose levels and resistance to diet-induced obesity as compared with the minor allele C. Based on the Kv1.3 genotype, the TDI and I olfactory scores obtained by the subjects were the following: TT > TC > CC. Subjects who were TT homozygous or heterozygous exhibited lower BMIs and reached higher olfactory scores than those with the CC genotype. The results were sex-dependent: heterozygous females performed better than heterozygous males. These findings show an inverse relationship between olfactory function and BMI, and a significant effect of the Kv1.3 genotypes on the olfactory functions and on the BMIs of the subjects. Finally, they suggest that the sex-related differences in the olfactory function can be partially ascribed to the Kv1.3 gene’s polymorphism.

Individual differences in sweet taste sensitivity can affect dietary preferences as well as nutritional status. Despite the lack of consensus, it is believed that sweet taste is impacted by genetic and environmental variables. Here we determined the effect of well-established factors influencing the general taste variability, such as gender and fungiform papillae density, specific genetic variants (SNPs of TAS1R2 and TAS1R3 receptors genes), and non-specific genetic factors (PROP phenotype and genotype), on the threshold and suprathreshold sweet taste sensitivity. Suprathreshold measurements showed that the sweet taste response increased in a dose-dependent manner, and this was related to PROP phenotype, gender, rs35874116 SNP in the TAS1R2 gene, and rs307355 SNP in the TAS1R3 gene. The threshold values and density of fungiform papillae exhibited a strong correlation, and both varied according to PROP phenotype. Our data confirm the role of PROP taste status in the sweet perception related to fungiform papilla density, show a higher sweet sensitivity in females who had lower BMI than males, and demonstrate for the first time the involvement of the rs35874116 SNP of TAS1R2 in the sweet taste sensitivity of normal weight subjects with body mass index (BMI) ranging from 20.2 to 24.8 kg/m 2 . These results may have an important impact on nutrition and health mostly in subjects with low taste ability for sweets and thus with high vulnerability to developing obesity or metabolic disease.

Among the factors that contribute to the physiological variability of the olfactory function of individuals, an important role seems to be played by the OBPs present in the mucus that bathes the ciliated terminals of the olfactory sensory neurons, facilitating the access of odorants to the olfactory receptors. It was recently highlighted that the rs2590498 polymorphism in the odor binding-protein (OBPIIa) gene it is associated with the olfactory threshold in healthy individuals. Aim of this study was to evaluate: 1) the presence of a relationship between the threshold olfactory performance of healthy subjects and the intensity with which they perceive the smelled odorants, and 2) the effect of the rs2590498 polymorphism of the OBPIIa gene on perceived intensity. We found a positive correlation between threshold olfactory and perceived intensity, and that AA homozygous subjects reported a perceived intensity higher than heterozygous and GG homozygous subjects. By showing a positive effect of the rs2590498 polymorphism of the hOBPIIa gene on the intensity perceived, these results suggest that it allows a larger number of molecules in an odorous mixture to reach the olfactory receptors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Diet and salivary proteins influence the composition of the oral microbiome, and recent data suggest that TAS2R38 bitter taste genetics may also play a role. We investigated the effects of daily exposure to a cranberry polyphenol oral rinse on taste perception, salivary proteins, and oral microbiota. 6-n-Propylthiouracil (PROP) super-tasters (ST, n = 10) and non-tasters (NT, n = 10) rinsed with 30 mL of 0.75 g/L cranberry polyphenol extract (CPE) in spring water, twice daily for 11 days while consuming their habitual diets. The 16S rRNA gene sequencing showed that the NT oral microbiome composition was different than that of STs at baseline ( p = 0.012) but not after the intervention ( p = 0.525). Principal coordinates analysis using unweighted UniFrac distance showed that CPE modified microbiome composition in NTs ( p = 0.023) but not in STs ( p = 0.096). The intervention also altered specific salivary protein levels (α-amylase, MUC-5B, and selected S-type Cystatins) with no changes in sensory perception. Correlation networks between oral microbiota, salivary proteins, and sensory ratings showed that the ST microbiome had a more complex relationship with salivary proteins, particularly proline-rich proteins, than that in NTs. These findings show that CPE modulated the oral microbiome of NTs to be similar to that of STs, which could have implications for oral health.

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.

Deficits in olfaction and taste are among the most frequent non-motor manifestations in Parkinson's disease (PD) that start very early and frequently precede the PD motor symptoms. The limited data available suggest that the basis of the olfactory and gustatory dysfunction related to PD are likely multifactorial and may include the same determinants responsible for other non-motor symptoms of PD. This review describes the most relevant molecular and genetic factors involved in the PD-related smell and taste impairments, and their associations with the microbiota, which also may represent risk factors associated with the disease.

Taste plays an important role in processes such as food choices, nutrition status and health. Salivary proteins contribute to taste sensitivity. Taste reduction has been associated with obesity. Gender influences the obesity predisposition and the genetic ability to perceive the bitterness of 6- n -propylthiouracil (PROP), oral marker for food preferences and consumption. We investigated variations in the profile of salivary proteome, analyzed by HPLC-ESI-MS, between sixty-one normal weight subjects (NW) and fifty-seven subjects with obesity (OB), based on gender and PROP sensitivity. Results showed variations of taste-related salivary proteins between NW and OB, which were differently associated with gender and PROP sensitivity. High levels of Ps-1, II-2 and IB-1 proteins belonging to basic proline rich proteins (bPRPs) and PRP-1 protein belonging to acid proline rich proteins (aPRPs) were found in OB males, who showed a lower body mass index (BMI) than OB females. High levels of Ps-1 protein and Cystatin SN (Cyst SN) were found in OB non-tasters, who had lower BMI than OB super-tasters. These new insights on the role of salivary proteins as a factor driving the specific weight gain of OB females and super-tasters, suggest the use of specific proteins as a strategic tool modifying taste responses related to eating behavior.

Most odors of foods and drinks are mixtures of molecules. By means of the coupled Gas Chromatography-Olfactometry (GC-O) technique, single components of flavor mixtures can be separated, identified and verbally evaluated by subjects. The number of single molecules smelled by subjects during GC-O analysis (i.e., the number of odor-active compounds) was previously found to be linearly correlated with odor Threshold (T) score. Using the "Sniffin' Sticks" test, the same subjects were classified as normosmic or hyposmic. Hydrophobic odorants are captured and transported through the mucus layer by the odorant binding proteins (OBPs), particularly expressed in the olfactory cleft and associated with the olfactory function. In this study, subjects were genotyped for the rs2590498 (A/G) polymorphism of the OBPIIa gene, whose major allele A is associated with a higher olfactory sensitivity as compared to the minor allele G. One-way ANOVA showed a significant effect of the genotype of the OBPIIa locus on the: a) T score; b) number of odor-active compounds smelled; c) intensity perceived when sniffing the complex odor of banana. In conclusion, the threshold olfactory performance, but also the individual ability to smell single molecules, can be attributed, partly at least, to the rs2590498 polymorphism of the OBPIIa gene., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Astringency is a complex oral sensation, commonly experienced when dietary polyphenols interact with salivary proteins. Most astringent stimuli alter protein levels, which then require time to be replenished. Although it is standard practice in astringency research to provide breaks in between stimuli, there is limited consensus over the amount of time needed to restore the oral environment to baseline levels. Here we examined salivary protein levels after exposure to 20 mL of a model stimulus (cranberry polyphenol extract, 0.75 g/L CPE) or unsweetened cranberry juice (CJ), over a 10 min period. Whole saliva from healthy subjects ( n = 60) was collected at baseline and after 5 and 10 min following either stimulus. Five families of proteins: basic proline-rich proteins (bPRPs); acidic proline-rich proteins (aPRPs); histatins; statherin; and S-type cystatins, were analyzed in whole saliva via HPLC-low resolution-ESI-IT-MS, using the area of the extracted ion current (XIC) peaks. Amylase was quantified via immunoblotting. In comparison to baseline (resting), both stimuli led to a rise in levels of aPRPs ( p < 0.000) at 5 min which remained elevated at 10 min after stimulation. Additionally, an interaction of PROP taster status and time was observed, wherein super-tasters had higher levels of amylase in comparison to non-tasters after stimulation with CJ at both timepoints ( p = 0.014-0.000). Further, male super-tasters had higher levels of bPRPs at 5 min after stimulation with both CJ and CPE ( p = 0.015-0.007) in comparison to baseline. These data provide novel findings of interindividual differences in the salivary proteome that may influence the development of astringency and that help inform the design of sensory experiments of astringency.

Humans can accurately discern thousands of odorants, although there is a considerable inter-individual variability. Individuals can be classified as normosmic, hyposmic or anosmic, depending on their olfactory sensitivity or blindness. In this research we studied the olfactory sensitivity to banana head-space as a complex odor mixture in a group of 53 subjects classified for their olfactory status, by means of the "Sniffin' Sticks" extended test. Using the coupled Gas Chromatography-Mass Spectrometry/ Olfactometry (GC-MS/O) technique, the single components of the banana flavor mixture were separated, identified and verbally evaluated by each subject. For each compound both the "odor type" (i.e., odor quality: fruity, floral, green, etc.) and "odor descriptor" (i.e., name used by subjects for odor identification) were reported, so that we could identify molecules that were defined as smelling of banana. The results show that: (a) the threshold olfactory performance is linearly correlated with the number of odor-active compounds (total or smelling of banana) for each subject; (b) the intensity reported by each subject during the sniffing of the pen containing the banana aroma in the identification test is positively correlated both with its hedonic valence and the number of odor-active compounds smelling of banana. In conclusion, our findings show that human perception of single compounds is conditioned by the threshold olfactory performance of the subject and that his/her ability to detect single molecular components, which smell as the mixture, affects the intensity and hedonism for the complex aroma., Competing Interests: Declaration of Competing Interests All authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Among non-motor manifestations of Parkinson's Disease (PD), peripheral, sensory symptoms are particularly relevant. Smell dysfunction starts very early and frequently precedes the PD motor symptoms by years (being often a cue to the diagnosis). Moreover, olfactory system could be, together with gut, one of those peripheral sites where PD pathology first develops. Unlike smell loss, the relationship between PD and taste impairment is far less established. It can start early in the course of the disease but more frequently appears in advanced stages, in parallel with the advent of MCI, likely reflecting cortical involvement. Among PD patients has been demonstrated an increase in the frequency of the non-tasters for PROP (prototypical gustatory stimulus, 6- n-propylthiouracil), a genetically determined bitter taste which is mediated by TAS2RS38 receptor, and a significant increase of the recessive non-testing variant of this receptor. TAS2R38 receptors are expressed also in other tissues, such as in the epithelia of the gut and nasal cavities, where they can influence epithelial immunity ad its interaction with microbiota. Those pieces of evidence suggest that not only systematic assessment of taste and smell can be of a remarkable help for clinicians in the early diagnosis, but also that understanding the mechanisms of sensory involvement in PD could increase the knowledge of the pathophysiology of the disease., (Copyright © 2020 Oppo, Melis, Melis, Tomassini Barbarossa and Cossu.)

Bitter taste receptors play crucial roles in detecting bitter compounds not only in the oral cavity, but also in extraoral tissues where they are involved in a variety of non‒tasting physiological processes. On the other hand, disorders or modifications in the sensitivity or expression of these extraoral receptors can affect physiological functions. Here we evaluated the role of the bitter receptor TAS2R38 in attainment of longevity, since it has been widely associated with individual differences in taste perception, food preferences, diet, nutrition, immune responses and pathophysiological mechanisms. Differences in genotype distribution and haplotype frequency at the TAS2R38 gene between a cohort of centenarian and near-centenarian subjects and two control cohorts were determined. Results show in the centenarian cohort an increased frequency of subjects carrying the homozygous genotype for the functional variant of TAS2R38 (PAV/PAV) and a decreased frequency of those having homozygous genotype for the non-functional form (AVI/AVI), as compared to those determined in the two control cohorts. In conclusion, our data providing evidence of an association between genetic variants of TAS2R38 gene and human longevity, suggest that TAS2R38 bitter receptor can be involved in the molecular physiological mechanisms implied in the biological process of aging.

Olfactory function varies by several orders of magnitude among healthy individuals, who may exhibit a reduced sensitivity (hyposmia), a high sensitivity (hyperosmia), or an olfactory blindness (anosmia). Environmental and genetic factors seem to account for this variability. Most of odorant molecules are hydrophobic and it has been suggested that odorants are transported to the olfactory receptors by means of odorant binding proteins (OBPs). Aim of this study was to evaluate the presence of a relationship between the olfactory performance of healthy subjects and the polymorphism in the odor binding-protein (OBPIIa) gene, the only OBP found in the olfactory epithelium of humans. Using the "Sniffin' Sticks" Extended Test we assessed the olfactory performance in 69 subjects, who were genotyped for the rs2590498 polymorphism of the OBPIIa gene, whose major allele A has been associated with a higher retronasal perception as compared to the minor allele G. We found that subjects homozygous for the A-allele exhibited threshold scores higher than subjects homozous for the G-allele or heterozygous. In addition, subjects classified as normosmic and hyposmic differed on the basis of genotype distribution and allelic frequencies. In fact, a normosmic condition was associated with genotype AA and allele A and a hyposmic condition was associated with genotype GG and allele G. In conclusion, our results show that a relationship exists between the physiological variations of olfactory performance and the OBPIIa gene polymorphism., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives/hypothesis: Taste sensitivity varies greatly among individuals influencing eating behavior and health, consequently the disorders of this sense can affect the quality of life. The ability to perceive the bitter of thiourea compounds, such as phenylthiocarbamide (PTC), has been largely reported as a marker of the general taste sensitivity, food preferences, and health. PTC sensitivity is mediated by the TAS2R38 receptor and its genetic common variants. We study the role of the TAS2R38 receptor in taste disorders with the aim of understanding if these can be genetically determined., Study Design: Prospective cohort study., Methods: Differences in the PTC responsiveness between the patients cohort and healthy controls were assessed. All subjects received standardized tests for smell and taste function and were genotyped for the TAS2R38 gene., Results: PAV/PAV homozygous patients gave high PTC ratings, whereas PAV/AVI genotypes reported lower values, which are similar to those determined in AVI/AVI or rare genotypes. In addition, the patients cohort did not meet the Hardy-Weinberg equilibrium at the TAS2R38 locus, showing a very low frequency of subjects carrying the PAV/AVI diplotype. Independently, in healthy controls who were in equilibrium at the locus, PAV/PAV homozygous and heterozygous rated PTC bitterness higher compared to AVI/AVI or rare genotypes., Conclusions: Our findings, by showing that an only taster haplotype (PAV) is not sufficient to evoke high responses of TAS2R38 receptor in patients with taste disorders, suggest that the genetic constitution may represent a risk factor for the development of taste disorders., Level of Evidence: 2c Laryngoscope, 129:E307-E312, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Deficits in olfaction are among the most frequent non-motor symptoms in Parkinson's disease (PD) and can be detected early compared with motor symptoms. The reason for the early onset, as well as the mechanism involved remains unknown. We aimed to characterize the olfactory performance of patients with PD and age-matched healthy control (HC) participants in association with gender and a specific polymorphism in the odorant-binding protein IIa (OBPIIa) gene, which plays a crucial role in the perception of odors. The olfactory performance was assessed using the odor identification part of the Sniffin' Sticks test in 249 participants (patients with PD: n = 131 and HC participants: n = 118). All participants were genotyped for the rs2590498 polymorphism of the OBPIIa gene, whose major allele A is associated with a higher retronasal perception than the minor allele G. A higher number of men with PD than women with PD exhibited hyposmia. Importantly, OBPIIa gene polymorphism showed an effect on PD-related olfactory deficits only in women. Women with PD carrying two sensitive alleles (AA) showed a better olfactory performance than women with PD with at least one insensitive allele (G); the olfactory scores of the AA genotype women with PD were not different from those of HC participants. In conclusion, our results confirmed a sex effect on the reduced olfactory performance of patients with PD and identified the OBPIIa locus, which may provide a mechanism to determine the risk factor for olfactory deficits in women with PD at the molecular level., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The perception of fat varies among individuals and has also been associated with CD36 rs1761667 polymorphism and genetic ability to perceive oral marker 6-n-propylthiouracil (PROP). Nevertheless, data in the literature are controversial. We present direct measures for the activation of the peripheral taste system in response to oleic acid by electrophysiological recordings from the tongue of 35 volunteers classified for PROP taster status and genotyped for CD36 . The waveform of biopotentials was analyzed and values of amplitude and rate of potential variation were measured. Oleic acid stimulations evoked positive monophasic potentials, which represent the summated voltage change consequent to the response of the stimulated taste cells. Bio-electrical measurements were fully consistent with the perceived intensity during stimulation, which was verbally reported by the volunteers. ANOVA revealed that the amplitude of signals was directly associated, mostly in the last part of the response, with the CD36 genotypes and PROP taster status (which was directly associated with the density of papillae). The rate of potential variation was associated only with CD36, primarily in the first part of the response. In conclusion, our results provide direct evidence of the relationship between fat perception and rs1761667 polymorphism of the CD36 gene and PROP phenotype.

Background: The few studies that evaluated taste function in Parkinson's disease (PD) showed inconsistent results. The inherited ability to taste the bitter compound of 6-n-propylthiouracil has been considered to be a paradigm of general taste perception. 6-n-propylthiouracil taste perception is mediated by the TAS2R38 receptor, and reduced 6-n-propylthiouracil sensitivity has been associated with several diseases not typically related to taste function., Objectives: We evaluated the 6-n-propylthiouracil taste perception and the TAS2R38 gene as genetic risk factors for the development of idiopathic PD in PD patients and healthy controls (HC)., Methods: The 6-n-propylthiouracil taste perception was assessed by testing the responsiveness, and the ability to recognize, 6-n-propylthiouracil and sodium chloride. The participants were classified for 6-n-propylthiouracil taster status and genotyped for the TAS2R38 gene., Results: A significant increase in the frequency of participants classified as 6-n-propylthiouracil nontasters and a reduced ability to recognize bitter taste quality of 6-n-propylthiouracil were found in PD patients when compared with healthy controls. The results also showed that only 5% of PD patients had the homozygous genotype for the dominant tasting variant of TAS2R38, whereas most of them carried the recessive nontaster form and a high number had a rare variant., Conclusions: Our results show that 6-n-propylthiouracil taster status and TAS2R38 locus are associated with PD. The 6-n-propylthiouracil test may therefore represent a novel, simple way to identify increased vulnerability to PD. Moreover, the presence of the nontasting form of TAS2R38 in PD may further substantiate that disease-associated taste disruption may represent a risk factor associated with the disease. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)

Previous studies demonstrate humans can detect fatty acids via specialized sensors on the tongue, such as the CD36 receptor. Genetic variation at the common single nucleotide polymorphism rs1761667 of CD36 has been shown to differentially impact the perception of fatty acids, but comparative data among different ethnic groups are lacking. In a small cohort of Caucasian and East Asian young adults, we investigated if: (1) participants could detect oleic acid (C18:1) added to safflower oil emulsions at a constant ratio of 3% (w/v); (2) supplementation of oleic acid to safflower oil emulsions enhanced perception of fattiness and creaminess; and (3) variation at rs1761667 influenced oleic acid detection and fat taste perception. In a 3-alternate forced choice test, 62% of participants detected 2.9 ± 0.7 mM oleic acid (or 0.08% w/v) in a 2.8% safflower oil emulsion. Supplementation of oleic acid did not enhance fattiness and creaminess perception for the cohort as a whole, though East Asians carrying the GG genotype perceived more overall fattiness and creaminess than their AA genotype counterparts (P < 0.001). No differences were observed for the Caucasians. These preliminary findings indicate that free oleic acid can be detected in an oil-in-water emulsion at concentrations found in commercial oils, but it does not increase fattiness or creaminess perception. Additionally, variation at rs1761667 may have ethnic-specific effects on fat taste perception., (© 2018 The Authors Journal of Food Science published by Wiley Periodicals, Inc. on behalf of Institute of Food Technologists.)

Oral sensitivity to fats varies in individuals influencing nutritional status and health. Variations in oleic acid perception are associated with CD36 and odorant binding protein (OBPIIa) polymorphisms, and 6-n-propylthiouracil (PROP) sensitivity, which is mediated by TAS2R38 receptor. L-Arginine (L-Arg) supplementation was shown to modify the perception of the five taste qualities. Here we analyzed the effect of three concentrations (5, 10, 15 mmol/L) of L-Arg on oral perception of oleic acid in forty-six subjects classified for PROP taster status and genotyped for TAS2R38, CD36 and OBPIIa polymorphisms. L-Arg supplementation was effective in increasing the perceived intensity of oleic acid in most subjects. The lowest concentration was the most effective, especially in PROP non-tasters or medium tasters, and in subjects with at least an allele A in CD36 and OBPIIa loci. Density Functional Theory (DFT) calculations were exploited to characterize the chemical interaction between L-Arg and oleic acid, showing that a stable 1:1 oleate·ArgH+ adduct can be formed, stabilized by a pair of hydrogen bonds. Results indicate that L-Arg, acting as a 'carrier' of fatty acids in saliva, can selectively modify taste response, and suggest that it may to be used in personalized dietetic strategies to optimize eating behaviors and health.

The multifunctional CD36 scavenger receptor facilitates fatty acid (FA) uptake and oxidation and it has been involved in the pathophysiology related to dysfunctional FA metabolism. The common variant in the CD36 gene, rs1761667 (A/G), whose allele A is characterized by a reduced protein expression, has been associated with taste sensitivity to and preference for fat. We therefore aimed at evaluating whether the CD36 polymorphism may influence fatty acid metabolism and endocannabinoid biosynthesis in normal weight (NW) and obese (OB) subjects. Red blood cell (RBC) fatty acid composition, and plasma endocannabinoid levels were determined. In NW subjects with AA genotype was found a marked reduction of RBC saturated fatty acids and palmitic/linoleic ratio (PA/LA), considered as de novo lipogenesis (DNL) biomarkers. Remarkably, to the reduction of DNL biomarkers corresponded an increase of omega-6 index, an indirect marker of the impact on fatty acid metabolism of dietary omega-6 fatty acids, endocannabinoid levels and a higher waist/hip ratio. The presence of the G allele was instead associated with increased endocannabinoid plasma levels and a trend for increased waist/hip ratio in obese subjects, even though exhibited decreased BMI with respect to those with AA genotype. These data indicate that the CD36 polymorphism, rs1761667 , leads to a distinct metabolic pattern in NW and in OB subjects. Therefore, their determination may be crucial in developing personalized therapeutic strategies for ameliorating dyslipidemia and other metabolic disorders.

In the last several decades, the genetic ability to taste the bitter compound, 6- n -propyltiouracil (PROP) has attracted considerable attention as a model for understanding individual differences in taste perception, and as an oral marker for food preferences and eating behavior that ultimately impacts nutritional status and health. However, some studies do not support this role. This review describes common factors that can influence the characterization of this phenotype including: (1) changes in taste sensitivity with increasing age; (2) gender differences in taste perception; and (3) effects of smoking and obesity. We suggest that attention to these factors during PROP screening could strengthen the associations between this phenotype and a variety of health outcomes ranging from variation in body composition to oral health and cancer risk., Competing Interests: The authors declare no conflict of interest.

The goal of this work is to develop an automatic system for the evaluation of the gustatory sensitivity of patients using an electrophysiological recording of the response of bud cells to taste stimuli. In particular, the study aims to evaluate the effectiveness and limitations of supervised classifiers in the discrimination between subjects belonging to the three 6-n-propylthiouracil (PROP) taster categories (supertasters, medium tasters, and non-tasters), exploiting features extracted from electrophysiological recordings of the tongue. Thirty-nine subjects (equally divided into the three PROP status classes by standard non-objective scaling methods) underwent a non-invasive, differential, biopotential recording of their tongues during stimulation with PROP by using a custom-made, flexible, silver electrode. Two different classifiers were trained to recognize up to seven different features extracted from the recorded depolarization signal. The classification results indicate that the identified set of features allows to distinguish between PROP tasters and non-tasters (average accuracy of 80% ± 18% and up to 94% ± 15% when only supertasters and non-tasters are considered), but medium tasters were difficult to identify. However, these apparent classification errors are related to uncertainty in the labeling procedures, which are based on non-objective tests, in which the subjects provided borderline evaluations. Thus, using the proposed method, it is possible, for the first time, to automatically achieve objective PROP taster status identification with high accuracy. The simplicity of the recording technique allows for easy reproduction of the experimental setting; thus the technique can be used in future studies to evaluate other gustatory stimuli. The proposed approach represents the first objective and automatic method to directly measure human gustatory responses and a milestone for physiological taste studies, with applications ranging from basic science to food tasting evaluations.

Deeper understanding of signaling mechanisms underlying bitterness perception in people is essential for designing novel and effective bitter blockers, which could enhance nutrition and compliance with orally administered bitter-tasting drugs. Here we show that variability in a human odorant-binding protein gene, OBPIIa, associates with individual differences in bitterness perception of fat (oleic acid) and of a prototypical bitter stimulus, 6-n-propylthiouracil (PROP), suggesting a novel olfactory role in the modulation of bitterness sensitivity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Behavioral reaction to different taste qualities affects nutritional status and health. 6- n -Propylthiouracil (PROP) tasting has been reported to be a marker of variation in taste perception, food preferences, and eating behavior, but results have been inconsistent. We showed that l-Arg can enhance the bitterness intensity of PROP, whilst others have demonstrated a suppression of the bitterness of quinine. Here, we analyze the taste perception of sweet, sour, salty, bitter, and umami and the modifications caused by l-Arg supplementation, as a function of PROP-taster status. Taste perception was assessed by testing the ability to recognize, and the responsiveness to, representative solutions of the five primary taste qualities, also when supplemented with l-Arg, in subjects classified as PROP-tasting. Super-tasters, who showed high papilla density, gave higher ratings to sucrose, citric acid, caffeine, and monosodium l-glutamate than non-tasters. l-Arg supplementation mainly modified sucrose perception, enhanced the umami taste, increased NaCl saltiness and caffeine bitterness only in tasters, and decreased citric acid sourness. Our findings confirm the role of PROP phenotype in the taste perception of sweet, sour, and bitter and show its role in umami. The results suggest that l-Arg could be used as a strategic tool to specifically modify taste responses related to eating behaviors., Competing Interests: The authors declare no conflict of interest.

Individual differences in astringency perception are poorly understood. Astringency from tannins stimulates the release of specific classes of salivary proteins. These proteins form complexes with tannins, altering their perceived astringency and reducing their bioavailability. We studied the bitter compound, 6-n-propylthioural (PROP), as a phenotypic marker for variation in astringency perception and salivary protein responses. Seventy-nine subjects classified by PROP taster status rated cranberry juice cocktail (CJC; with added sugar) supplemented with 0, 1.5 or 2.0g/L tannic acid (TA). Saliva for protein analyses was collected at rest, or after stimulation with TA or cranberry juice (CJ; without added sugar). CJC with 1.5g/L tannic acid was found to be less astringent, and was liked more by PROP non-taster males than PROP taster males, consistent with the expectation that non-tasters are less sensitive to astringency. Levels of acidic Proline Rich Proteins (aPRPs) and basic Proline Rich Proteins (bPRPs) decreased after TA, while levels of aPRPs, bPRPs and Cystatins unexpectedly rose after CJ. Increases in bPRPs and Cystatins were only observed in PROP tasters. The PROP phenotype plays a gender-specific, but somewhat limited role in the perceived astringency of tannic-acid supplemented, cranberry juice cocktail. The PROP phenotype (regardless of gender) may also be involved in the release of salivary proteins previously implicated in oral health., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Practical and reliable methods for the objective measure of taste function are critically important for studying eating behavior and taste function impairment. Here, we present direct measures of human gustatory response to a prototypical bitter compound, 6-n-propyltiouracil (PROP), obtained by electrophysiological recordings from the tongue of subjects who were classified for taster status and genotyped for the specific receptor gene (TAS2R38), and in which taste papilla density was determined. PROP stimulation evoked negative slow potentials that represent the summated depolarization of taste cells. Depolarization amplitude and rate were correlated with papilla density and perceived bitterness, and associated with taster status and TAS2R38. Our study provides a robust and generalizable research tool for the quantitative measure of peripheral taste function, which can greatly help to resolve controversial outcomes on the PROP phenotype role in taste perception and food preferences, and be potentially useful for evaluating nutritional status and health.

Genetic variation in the ability to taste the bitterness of 6-n-propylthiouracil (PROP) is a complex trait that has been used to predict food preferences and eating habits. PROP tasting is primarily controlled by polymorphisms in the TAS2R38 gene. However, a variety of factors are known to modify the phenotype. Principle among them is the salivary protein Ps-1 belonging to the basic proline-rich protein family (bPRP). Recently, we showed that oral supplementation with Ps-1 as well as its related free amino acids (L-Arg and L-Lys) enhances PROP bitterness perception, especially for PROP non-tasters who have low salivary levels of Ps-1. Here, we show that salivary L-Arg levels are higher in PROP super-tasters compared to medium tasters and non-tasters, and that oral supplementation with free L-Arg enhances PROP bitterness intensity as well as reduces bitterness latency in a dose-dependent manner, particularly in individuals with low salivary levels of both free L-Arg and Ps-1 protein. Supplementation with L-Arg also enhanced the bitterness of caffeine. We also used 1H-NMR spectroscopy and quantum-mechanical calculations carried out by Density Functional Theory (DFT) to characterize the chemical interaction between free L-Arg and the PROP molecule. Results showed that the -NH2 terminal group of the L-ArgH+ side chain interacts with the carbonyl or thiocarbonyl groups of PROP by forming two hydrogen bonds with the resulting charged adduct. The formation of this PROP•ArgH+ hydrogen-bonded adduct could enhance bitterness intensity by increasing the solubility of PROP in saliva and its availability to receptor sites. Our data suggest that L-Arg could act as a 'carrier' of various bitter molecules in saliva.

Herbivorous animals may benefit from the capability to discriminate the taste of bitter compounds since plants produce noxious compounds, some of which toxic, while others are only unpalatable. Our goal was to investigate the contribution of the peripheral taste system in the discrimination of different bitter compounds by an herbivorous insect using the larvae of Papilio hospiton Géné as the experimental model, showing a narrow choice range of host plants. The spike activity from the lateral and medial styloconic sensilla, housing two and one bitter-sensitive gustatory receptor neurons (GRNs), respectively, was recorded following stimulation with nicotine, caffeine, salicin and quercitrin and the time course of the discharges was analyzed. Nicotine and caffeine activated all three bitter-sensitive GRNs, while salicin and quercitrin affected only two of them. In feeding behavior bioassays, intact larvae ate glass-fiber disks moistened with salicin and quercitrin, but rejected those with nicotine and caffeine, while lateral sensillum-ablated insects also ate the disks with the two latter compounds. The capability to discriminate bitter taste stimuli and the neural codes involved are discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Taste sensitivity to the bitter compound 6-n-propylthiouracil (PROP) is considered a marker for individual differences in taste perception that may influence food preferences and eating behavior, and thereby energy metabolism. This review describes genetic factors that may contribute to PROP sensitivity including: (1) the variants of the TAS2R38 bitter receptor with their different affinities for the stimulus; (2) the gene that controls the gustin protein that acts as a salivary trophic factor for fungiform taste papillae; and (3) other specific salivary proteins that could be involved in facilitating the binding of the PROP molecule with its receptor. In addition, we speculate on the influence of taste sensitivity on energy metabolism, possibly via modulation of the endocannabinoid system, and its possible role in regulating body composition homeostasis.

In herbivorous insects, food selection depends on sensitivity to specific chemical stimuli from host-plants as well as to secondary metabolites (bitter) and to sugars (phagostimulatory). Bitter compounds are noxious, unpalatable or both and evoke an aversive feeding response. Instead, sugars and sugar alcohols play a critical role in determining and enhancing the palatability of foods. We assumed that peripheral taste sensitivity may be related to the width of the host selection. Our model consists of two closely phylogenetically related Papilionid species exhibiting a difference in host plant choice: Papilio hospiton and Papilio machaon. The spike activity of the lateral and medial maxillary styloconic taste sensilla was recorded following stimulation with several carbohydrates, nicotine and NaCl, with the aim of characterizing their gustatory receptor neurons and of comparing their response patterns in the light of their different acceptability in feeding behaviour. The results show that: a) each sensillum houses phagostimulant and phagodeterrent cells; b) the spike activity of the gustatory neurons in response to different taste stimuli is higher in P. hospiton than in P. machaon; c) sugar solutions inhibit the spike activity of the deterrent and salt cells, and the suppression is higher in P. machaon than in P. hospiton. In conclusion, we propose that the different balance between the phagostimulant and phagodeterrent inputs from GRNs of maxillary sensilla may contribute in determining the difference in food choice and host range.

Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli.

Objective: A decreased sensitivity to 6-n-propylthiouracil (PROP) has been shown to be associated with increased energy intake and therefore an increased body mass index, although other studies have not confirmed this association, suggesting the involvement of other factors. We investigated whether the endocannabinoid system, which also modulates hunger/satiety and energy balance, plays a role in modulating eating behavior influenced by a sensitivity to PROP., Methods: The plasma profile of the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), and congeners of AEA, palmitoylethanolamide and oleylethanolamide (OEA), was determined in normal-weight PROP supertasters (STs) and PROP non-tasters (NTs). A cognitive eating behavior disorder was assessed by the Three-Factor Eating Questionnaire, which estimates dietary restraint, disinhibition, and perceived hunger., Results: The disinhibition score of NTs was higher than those of STs (P = 0.02). Moreover, in NTs, OEA was inversely correlated to the perceived hunger score (r = -0.7, P = 0.002), and AEA was positively correlated to the restraint score (r = 0.5, P = 0.04) and negatively to the perceived hunger score, although the latter correlation was at the limit of statistical significance (r = -0.47, P = 0.05). In addition, we found lower concentrations of AEA and 2-AG in the plasma of NT compared with ST subjects (AEA, P = 0.034; 2-AG, P = 0.003)., Conclusions: Our data suggest that a higher disinhibition behavior in NTs may be compensated in part, in normal-weight subjects, by the decrease of peripheral endocannabinoids to downregulate the hunger-energy intake circuitry., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Thiourea tasting can be predictive of individual differences in bitter taste responses, general food preferences and eating behavior, and could be correlated with saliva chemical composition. We investigated the possible relationship between PROP bitter taste responsiveness and the salivary proteome in subjects genotyped for TAS2R38 and gustin gene polymorphisms. Taste perception intensity evoked by PROP and NaCl solutions was measured in sixty-three volunteers (21 males, 42 females, age 25±3 y) to establish their PROP taster status, and 24 PROP super-tasters and 21 nontasters were selected to participate in the study. TAS2R38 and gustin gene molecular analysis were performed using PCR techniques. Qualitative and quantitative determination of salivary proteins was performed by HPLC-ESI-MS before and after PROP taste stimulation. PROP super-tastings was strongly associated with the 'taster' variant (PAV haplotype) of TAS2R38 and the A allele of rs2274333 polymorphism in the gustin gene and nontasting was associated with the minor alleles at both loci. ANOVA revealed that basal levels of II-2 and Ps-1 proteins, belonging to the basic proline-rich protein (bPRPs) family, were significantly higher in PROP super-taster than in nontaster un-stimulated saliva, and that PROP stimulation elicited a rapid increase in the levels of these same proteins only in PROP super-taster saliva. These data show for the first time that responsiveness to PROP is associated with salivary levels of II-2 peptide and Ps-1 protein, which are products of the PRB1 gene. These findings suggest that PRB1, in addition to TAS2R38 and gustin, could contribute to individual differences in thiourea sensitivity, and the expression of the PROP phenotype as a complex genetic trait.

The role of amiloride in the labellar responses to various taste stimuli in the blowfly Protophormia terraenovae was studied with the aim of ascertaining whether amiloride-sensitive cation conductances are present in the chemosensory systems of insects. Results include that: 1) amiloride has no effect on the "salt" cell response to any stimulus; 2) amiloride decreases the "sugar" cell response to fructose, but does not affect that to sucrose; 3) the effects of amiloride on the responses of the "water" cell and the "fifth" cell are less clearly definable, due to the probable superimposition of osmotic mechanisms in the former and the poorly known response modalities of the water. In conclusion, amiloride-sensitive receptor sites seem to exist also in insects. However, unlike most vertebrates investigated, they are principally located in the sugar receptor cell, not on the salt cell.

In the present investigation it is shown that a reflex change in the heart activity of Protophormia flies is evoked by olfactory stimulation with several volatile substances, and particularly with those which are repellent for blowflies. Among these, i-pentanal and hexanal vapours evoked a fast, highly persistent cardiac response, whereas in the case of hexanol and ammonia vapours the response resulted slower and could be suppressed as a function of repeated stimulation.