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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.

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.

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.

The gustatory, olfactory, and trigeminal systems are anatomically separated. However, they interact cognitively to give rise to oral perception, which can significantly affect health and quality of life. We built a Supervised Learning (SL) regression model that, exploiting participants’ features, was capable of automatically analyzing with high precision the self-ratings of oral sensitivity of healthy participants and patients with chemosensory loss, determining the contribution of its components: gustatory, olfactory, and trigeminal. CatBoost regressor provided predicted values of the self-rated oral sensitivity close to experimental values. Patients showed lower predicted values of oral sensitivity, lower scores for measured taste, spiciness, astringency, and smell sensitivity, higher BMI, and lower levels of well-being. CatBoost regressor defined the impact of the single components of oral perception in the two groups. The trigeminal component was the most significant, though astringency and spiciness provided similar contributions in controls, while astringency was most important in patients. Taste was more important in controls while smell was the least important in both groups. Identifying the significance of the oral perception components and the differences between the two groups provide important information to allow for more targeted examinations supporting both patients and healthcare professionals in clinical practice.

Orosensory perception of dietary fat varies in individuals, thus influencing nutritional status. Several studies associated fat detection and preference with CD36 or 6-n-propylthiouracil (PROP) sensitivity. Other studies have not confirmed the latter association. We analyzed the relationship between orosensory perception of oleic acid, two CD36 variants, and PROP tasting. Thresholds of oleic acid perception were assessed in 64 subjects using a modification of the three-alternative forced-choice procedure. Subjects were classified for PROP taster status and genotyped for TAS2R38 and CD36 (SNPs: rs1761667 and rs1527483). Subjects homozygous for GG of the rs1761667 polymorphism showed higher sensitivity to oleic acid than AA subjects. The capability to detect oleic acid was directly associated with TAS2R38 or PROP responsiveness. PROP non-tasters had a lower papilla density than tasters, and those with genotype GG of the rs1761667 polymorphism had lower oleic acid thresholds than PROP non-tasters with genotype AA. In conclusion, results showed a direct association between orosensory perception of oleic acid and PROP tasting or rs1761667 polymorphism of CD36, which play a significant role in PROP non-tasters, given their low number of taste papillae. Characterization of individual capability to detect fatty acids may have important nutritional implications by explaining variations in human fat preferences.

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.

TAS2R38 is the T2R receptor primarily associated with the innate immune response of the respiratory system. It activates a response mediated by nitric oxide (NO), which has been shown to inhibit the replication of SARS-CoV-2. TAS2R38 polymorphisms (SNPs) that decrease receptor functionality contributing to individual differences in susceptibility to airway infections. DNA methylation (DNAm) may affect gene expression influencing disease development, including COVID-19. We analyzed the effect of SARS-CoV-2 on the methylation pattern of TAS2R38 (at cg25481253, a CpG site located in the coding region) during infection and after the cessation of the exposure to the virus, also considering the disease severity and TAS2R38 SNPs. Our results showed a positive relationship between TAS2R38 DNAm levels and disease severity in the COVID-19 patients and a return to a normal state after the infection. In addition, our results showed an association between DNAm level and the TAS2R38 genotype in participants who recovered from the disease. PAV/PAV genotypes showed lower TAS2R38 DNAm levels than heterozygous and AVI homozygous. In conclusion, our results clearly indicate the involvement of TAS2R38 DNAm alteration in COVID-19 severity and suggest a role of the methylation changes at cg25481253 in the regulation of the TAS2R38 expression.

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.

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.

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.