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.
VilaPMThomasTLiuCPoeDShinJJ. The burden and epidemiology of eustachian tube dysfunction in adults. Otolaryngol Head Neck Surg. 2017;156(2):278-284.
2.
FlintPWCummingsCW. Cummings Otolaryngology–Head and Neck Surgery. 5th ed.Mosby/Elsevier; 2010.
3.
MuftahSMackenzieIFaragherBBrabinB. Prevalence of chronic suppurative otitis media (CSOM) and associated hearing impairment among school-aged children in Yemen. Oman Med J. 2015;30(5):358-365.
4.
PichicheroME. Otitis media. Pediatr Clin North Am. 2013;60(2):391-407.
5.
HarmesKMBlackwoodRABurrowsHLCookeJMVan HarrisonRPassamaniPP. Otitis media: diagnosis and treatment. Am Fam Physician. 2013;88(7):435-440.
6.
Nokso-KoivistoJMaromTChonmaitreeT. Importance of viruses in acute otitis media. Curr Opin Pediatr. 2015;27(1):110-115.
7.
MinamiSBMutaiHSuzukiT, et al. Microbiomes of the normal middle ear and ears with chronic otitis media. Laryngoscope. 2017;127(10):E371-E377.
8.
HeikkinenTChonmaitreeT. Importance of respiratory viruses in acute otitis media. Clin Microbiol Rev. 2003;16(2):230-241.
9.
LeeRJXiongGKofonowJM, et al. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest. 2012;122(11):4145-4159.
10.
LeeRJRosenPLSiebertAP, et al. Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest. 2014;124(3):1393-1405.
11.
ShahASBen-ShaharYMoningerTOKlineJNWelshMJ. Motile cilia of human airway epithelia are chemosensory. Science. 2009;325(5944):1131-1134.
12.
DeckmannKDeckmannKFilipskiK, et al. Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes. Proc Natl Acad Sci U S A. 2014;111(22):8287-8292.
13.
GerbeFSidotESmythDJ, et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature. 2016;529(7585):226-230.
14.
CareyRMWorkmanADYanCH, et al. Sinonasal T2R-mediated nitric oxide production in response to Bacillus cereus. Am J Rhinol Allergy. 2017;31(4):211-215.
15.
CareyRMChenBAdappaND, et al. Human upper airway epithelium produces nitric oxide in response to Staphylococcus epidermidis. Int Forum Allergy Rhinol. 2016;6(12):1238-1244.
16.
CareyRMWorkmanADYanCH, et al. Staphylococcus aureus triggers nitric oxide production in human upper airway epithelium. Int Forum Allergy Rhinol. 2015;5(9):808-813.
17.
YanCHHahnSMcMahonD, et al. Nitric oxide production is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity. Am J Rhinol Allergy. 2017;31(2):85-92.
18.
LeeRJHaririBMMcMahonDB, et al. Bacterial d-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells. Sci Signal. 2017;10(495):eaam7703.
19.
CareyRMWorkmanADYanCH, et al. Denatonium-induced sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes. Int Forum Allergy Rhinol. 2017;7(7):699-704.
20.
AdappaNDHowlandTJPalmerJN, et al. Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention. Int Forum Allergy Rhinol. 2013;3(3):184-187.
21.
AdappaNDFarquharDPalmerJN, et al. TAS2R38 genotype predicts surgical outcome in nonpolypoid chronic rhinosinusitis. Int Forum Allergy Rhinol. 2016;6(1):25-33.
22.
AdappaNDTruesdaleCMWorkmanAD, et al. Correlation of T2R38 taste phenotype and in vitro biofilm formation from nonpolypoid chronic rhinosinusitis patients. Int Forum Allergy Rhinol. 2016;6(8):783-791.
23.
BartoshukLMDuffyVBReedDWilliamsA. Supertasting, earaches and head injury: genetics and pathology alter our taste worlds. Neurosci Biobehav Rev. 1996;20(1):79-87.
24.
ShawLMansfieldCColquittL, et al. Personalized expression of bitter “taste” receptors in human skin. PLoS One. 2018;13(10):e0205322.
25.
BehrensMFoersterSStaehlerFRaguseJDMeyerhofW. Gustatory expression pattern of the human TAS2R bitter receptor gene family reveals a heterogenous population of bitter responsive taste receptor cells. J Neurosci. 2007;27(46):12630-12640.
26.
LionT. Appropriate controls for RT-PCR. Leukemia. 1996;10(11):1843.
27.
DouglasJELinCMansfieldCJ, et al. Tissue-dependent expression of bitter receptor TAS2R38 mRNA. Chem Senses. 2019;44(1):33-40.
28.
WorkmanADBrooksSGKohanskiMABlasettiMT. Bitter and sweet taste tests are reflective of disease status in chronic rhinosinusitis. J Allergy Clin Immunol Pract. 2018;6(3):1078-1080.
29.
WorkmanADMainaIWBrooksSG, et al. The role of quinine-responsive taste receptor family 2 in airway immune defense and chronic rhinosinusitis. Front Immunol. 2018;9:624.
ChandrashekarJKuhnCOkaY, et al. The cells and peripheral representation of sodium taste in mice. Nature. 2010;464(7286):297-301.
32.
UpadhyayaJDChakrabortyRShaikFAJaggupilliABhullarRPChelikaniP. The pharmacochaperone activity of quinine on bitter taste receptors. PLoS One. 2016;11(5):e0156347.
33.
MeyerhofWBatramCKuhnC, et al. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses. 2010;35(2):157-170.
34.
KrouseJH. The unified airway—conceptual framework. Otolaryngol Clin North Am. 2008;41(2):257-266.
35.
LeeRJCohenNA. The emerging role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. Am J Rhinol Allergy. 2013;27(4):283-286.
WolfleUElsholzFAKerstenAHaarhausBSchumacherUSchemppCM. Expression and functional activity of the human bitter taste receptor TAS2R38 in human placental tissues and JEG-3 cells. Molecules. 2016;21(3):306.
38.
LeeRJCohenNA. Taste receptors in innate immunity. Cell Mol Life Sci. 2015;72(2):217-236.
39.
RyanAFBennettT. Nitric oxide contributes to control of effusion in experimental otitis media. Laryngoscope. 2001;111(2):301-305.
40.
AnderssonJAUddmanRTajtiJCardellLO. Heme oxygenase and nitric oxide synthase in human middle ear epithelium indicates local carbon monoxide and nitric oxide production. Acta Otolaryngol. 2002;122(6):634-637.
41.
SeppanenEJThorntonRBCorscaddenKJ, et al. High concentrations of middle ear antimicrobial peptides and proteins and proinflammatory cytokines are associated with detection of middle ear pathogens in children with recurrent acute otitis media. PLoS One. 2019;14(12):e0227080.
42.
HwangLDLinCGharahkhaniP, et al. New insight into human sweet taste: a genome-wide association study of the perception and intake of sweet substances. Am J Clin Nutr. 2019;109(6):1724-1737.
43.
LiX. T1R receptors mediate mammalian sweet and umami taste. Am J Clin Nutr. 2009;90(3):733S-737S.
44.
RissoDTofanelliSMoriniGLuiselliDDraynaD. Genetic variation in taste receptor pseudogenes provides evidence for a dynamic role in human evolution. BMC Evol Biol. 2014;14:198.
45.
RissoDSMezzavillaMPaganiL, et al. Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal. Sci Rep. 2016;6:25506.
46.
PydiSPUpadhyayaJSinghNBhullarRPChelikaniP. Recent advances in structure and function studies on human bitter taste receptors. Curr Protein Pept Sci. 2012;13(6):501-508.
47.
CareyRMLeeRJCohenNA. Taste receptors in upper airway immunity. Adv Otorhinolaryngol. 2016;79:91-102.
ShiffmanDEllisSGRowlandCM, et al. Identification of four gene variants associated with myocardial infarction. Am J Hum Genet. 2005;77(4):596-605.
50.
KochWHoppmannPSchömigAKastratiA. Variations of specific non-candidate genes and risk of myocardial infarction: a replication study. Int J Cardiol. 2011;147(1):38-41.
51.
BehrensMBrockhoffABatramCKuhnCAppendinoGMeyerhofW. The human bitter taste receptor hTAS2R50 is activated by the two natural bitter terpenoids andrographolide and amarogentin. J Agric Food Chem. 2009;57(21):9860-9866.
52.
YamadaYKuzuyamaTKomatsuM, et al. Terpene synthases are widely distributed in bacteria. Proc Natl Acad Sci U S A. 2015;112(3):857-862.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
