Worldwide study of the taste of bitter medicines and their modifiers.

The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canada immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for two of the five drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in one bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them.

Bitter Taste Receptors and Chronic Otitis Media.

OBJECTIVE: To evaluate the presence of bitter taste receptors (T2Rs) in the middle ear and to examine their relationship with chronic ear infections. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care hospital. METHODS: This study enrolled 84 patients being evaluated for otologic surgery: 40 for chronic otitis media (COM) and 44 for other surgical procedures (controls). We collected a small piece of mucosa from 14 patients for mRNA analysis and from 23 patients for immunohistochemistry. A total of 55 patients underwent a double-blind taste test to gauge sensitivity to phenylthiocarbamide, denatonium, quinine, sucrose, and sodium chloride; 47 patients gave a salivary sample for single-nucleotide polymorphism analysis of rs1376251 (TAS2R50) and rs1726866 (TAS2R38). RESULTS: Bitter taste receptors were found in all samples, but the repertoire varied among patients. T2R50 was the most consistently identified receptor by mRNA analysis. Its rs1376251 allele was related to susceptibility to COM but not the expression pattern of T2R50. Ratings of bitterness intensity of phenylthiocarbamide, a ligand for T2R38, differed significantly between the COM and control groups. CONCLUSION: T2Rs were found within the middle ear of every patient sampled; the rs1376251 allele of TAS2R50 appears to be related to chronic ear infections. These receptors are an intriguing target for future research and possible drug targeting.

Denatonium benzoate bitter taste perception in chronic rhinosinusitis subgroups.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls. METHODS: CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL-25 via flow cytometry. RESULTS: CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10-9 M, 1.00 × 10-8 M, 1.78 × 10-8 M, 3.16 × 10-8 M, 5.62 × 10-8 M, and 1.00 × 10-7 M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10-8 M and 3.16 × 10-8 M (p < 0.0083). In vitro data demonstrated significant increase in IL-25-positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012). CONCLUSION: Our findings link in vitro DB stimulation of sinonasal tissue with increased IL-25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10-8 M for future study of clinical utility.

Divergent bitter and sweet taste perception intensity in chronic rhinosinusitis patients.

BACKGROUND: Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses. METHODS: We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt. RESULTS: CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small. CONCLUSION: CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients.

Studies of human twins reveal genetic variation that affects dietary fat perception.

To learn more about the mechanisms of human dietary fat perception, 398 human twins rated fattiness and liking for six types of potato chips that differed in triglyceride content (2.5, 5, 10, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness and liking for the potato chips were reliable (r = 0.31-0.62, p < 0.05) and heritable (up to h2 = 0.29, p < 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, p < 1×10-5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was (a) negatively affected by the addition of a saturated fatty acid and (b) related to inborn genetic variants. These data suggest liking for dietary fat is not due solely to fatty acid content and highlight new candidate genes and proteins within this sensory pathway.

More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Personalized expression of bitter 'taste' receptors in human skin.

The integumentary (i.e., skin) and gustatory systems both function to protect the human body and are a first point of contact with poisons and pathogens. These systems may share a similar protective mechanism because, as we show here, both human taste and skin cells express mRNA for bitter 'taste' receptors (TAS2Rs). We used gene-specific methods to measure mRNA from all known bitter receptor genes in adult human skin from freshly biopsied samples and from samples collected at autopsy from the Genotype-Tissue Expression project. Human skin expressed some but not all TAS2Rs, and for those that were expressed, the relative amounts differed markedly among individuals. For some TAS2Rs, mRNA abundance was related to presumed sun exposure based on the location from which the skin sample was collected (TAS2R14, TAS2R30, TAS2R42, and TAS2R60), sex (TAS2R3, TAS2R4, TAS2R8, TAS2R9, TAS2R14, and TAS2R60), and age (TAS2R5), although these effects were not large. These findings contribute to our understanding of extraoral expression of chemosensory receptors.

Taste Exam: A Brief and Validated Test.

The emerging importance of taste in medicine and biomedical research, and new knowledge about its genetic underpinnings, has motivated us to supplement classic taste-testing methods in two ways. First, we explain how to do a brief assessment of the mouth, including the tongue, to ensure that taste papillae are present and to note evidence of relevant disease. Second, we draw on genetics to validate taste test data by comparing reports of perceived bitterness intensity and inborn receptor genotypes. Discordance between objective measures of genotype and subjective reports of taste experience can identify data collection errors, distracted subjects or those who have not understood or followed instructions. Our expectation is that fast and valid taste tests may persuade researchers and clinicians to assess taste regularly, making taste testing as common as testing for hearing and vision. Finally, because many tissues of the body express taste receptors, taste responses may provide a proxy for tissue sensitivity elsewhere in the body and, thereby, serve as a rapid, point-of-care test to guide diagnosis and a research tool to evaluate taste receptor protein function.