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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 ( TAS2R 38) 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.

The authors have withdrawn this manuscript owing to inaccuracies in the calculation of tuft cell numbers and errors in the selection of immunofluorescence images used to support our claims. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Purpose: The bad bitter taste of some medicines is a barrier to overcoming non-compliance with medication use, especially life-saving drugs given to children and the elderly. Here we evaluated a new class of bitter blockers (thiazolidinediones; TZDs)., Methods: In this study, two TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with two separate taste panels: a general panel (N=97, 20-23 yrs, 82.5% female, all Eastern European) and a genetically informative panel (N=158, including 68 twin pairs, 18-82 yrs, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale., Findings: Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the two panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD., Implications: These results suggest that TZDs are partially effective bitter blockers, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use., Competing Interests: Declarations of interest: none

T2R bitter receptors, encoded by Tas2r genes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and how Tas2r gene expression are regulated. Here we show that, in an inflammation model mimicking bacterial infection, the expression of many Tas2rs are significantly up-regulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. Using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility of Tas2rs was highly cell type specific and inflammation increased the accessibility of many Tas2rs . scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-term effects. Together, our results suggest an epigenetic mechanism connecting inflammation, Tas2r gene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.

How much pleasure we take in eating is more than just how much we enjoy the taste of food. Food involvement - the amount of time we spend on food beyond the immediate act of eating and tasting - is key to the human food experience. We took a biological approach to test whether food-related behaviors, together capturing food involvement, have genetic components and are partly due to inherited variation. We collected data via an internet survey from a genetically informative sample of 419 adult twins (114 monozygotic twin pairs, 31 dizygotic twin pairs, and 129 singletons). Because we conducted this research during the pandemic, we also ascertained how many participants had experienced COVID-19-associated loss of taste and smell. Since these respondents had previously participated in research in person, we measured their level of engagement to evaluate the quality of their online responses. Additive genetics explained 16-44% of the variation in some measures of food involvement, most prominently various aspects of cooking, suggesting some features of the human food experience may be inborn. Other features reflected shared (early) environment, captured by respondents' twin status. About 6% of participants had a history of COVID-19 infection, many with transitory taste and smell loss, but all but one had recovered before the survey. Overall, these results suggest that people may have inborn as well as learned variations in their involvement with food. We also learned to adapt to research during a pandemic by considering COVID-19 status and measuring engagement in online studies of human eating behavior.