Written by Henry P. Barham, MD, Mohamed A. Taha, MD, and Marianne Madsen

Bitter taste receptors (T2Rs), as the name implies, are known for their role in the perception of bitter taste. So one would expect their location to be only on the tongue. But recently, scientists discovered that these receptors were actually found beyond the oral cavity, in other parts of the body. This raises the question: What does a taste receptor in the respiratory tract do? This seemed weird at first glance, but when scientists studied these receptors extensively, they were able to elaborate their role in these unusual sites.

To understand the link between T2Rs and upper respiratory tract infections, you need to know some basic information about T2Rs. Let’s review a bit of the history surrounding the gene (coding for these receptors) and its relationship to upper respiratory infections in general–and to COVID-19 in particular.

Studies in Animals

Mammals have many different types of taste receptors. These include sweet, salty, sour, bitter, and savory (umami). Bitter taste is often associated with poisonous substances, so all mammals, including humans, have evolved to pay close attention to bitter-tasting substances, essentially improving their rate of survival. This ability has helped all mammals throughout time, as they discover new habitats, to avoid plants or other foods that they’ve never seen before that might be poisonous–if it tastes bitter, it might be toxic.

Scientists have been interested in the family of T2Rs for quite some time. For example, a 1997 study showed that rats have a strong response to things that taste bitter. Other studies, for example, one in 2013, showed that many other mammals have this same gene to detect bitter taste. This topic has been studied in an ongoing fashion—a 2017 study showed how the T2Rs genes help animals in the dog family avoid toxic substances.

Studies in Humans

Researchers have been interested in how T2Rs gene expression affects humans, too. It doesn’t seem as important now for humans to avoid bitter things that might be poisonous–we aren’t out trying to eat new plants that we’ve never seen before. So why do we still have these genes? What are they doing for us?

It turns out that these genes–in particular, the T2R38 gene–might not be as helpful for us when it comes to tasting bitter things as it was in the past, when we wondered if plants we had never seen before were toxic. However, expressing this gene means that you may be expressing many other related genes that are helping you in various ways. For example, these genes are related to longevity, may help you avoid colon cancer, and may prevent you from getting upper respiratory tract infections. 

In the respiratory tract, the role of T2Rs is to help you “taste” the infection. Sometimes it’s been called just that–”the bitter taste of infection.” Scientists discovered that T2Rs are present on the surface of some cells lining the respiratory tract, for example, epithelial ciliated cells and solitary chemosensory cells. When harmful pathogens (bacteria) enter the respiratory tract, they invade, multiply, and produce some toxic products that the T2Rs can sense. As a result, T2Rs get activated and cause those respiratory cells to produce very powerful substances capable of killing pathogens within minutes. So in a way, these receptors still act as “taste” receptors!

The T2R38 gene shows variation between individuals. Nearly 25% of people have the functional version of the gene–these are the “supertasters.” Another nearly 25% of people have the non-functional version–these are the “non-tasters.” The remaining 50%, the “tasters,” have some degree of functionality in their genes. So, supertasters–those who strongly react to the bitter taste of food or drink–have a better chance of combating upper respiratory tract infections. The expression of this gene also seems to be linked to age–older people have lower expression of this gene in comparison to their younger counterparts.     

Dr. Henry Barham, as a rhinologist (an ENT doctor who specializes in nose and sinus diseases and surgery), is one of the scientists who has been studying the role of the T2Rs in the upper respiratory tract for many years. He has been most interested in it in relation to rhinosinusitis (inflammation of the nose and sinuses), and he has done several studies in this area. When the COVID-19 pandemic started, he directed his knowledge about T2Rs toward this new virus, searching for a possible link. The results are amazing. 

Studies Specifically in COVID-19

Dr. Barham’s findings are impressive. His first study was retrospective—it looked back at people who had already been diagnosed with COVID-19. Out of the 100 patients included, 79 COVID-19 patients had mild to moderate symptoms that were managed successfully at home, while the remaining 21 COVID-19 patients had significant symptoms that required hospital admission. Astonishingly, the 79 patients that were managed at home were all tasters, and the 21 patients hospitalized were all non-tasters. You will even be more impressed to know that not one of the 100 COVID-19 patients were supertasters!   

His next study was prospective—it looked forward to the future. This time, almost 2,000 subjects who had never had COVID-19 were tested to see what taste group they were in, then tracked. When these subjects eventually contracted COVID-19, Dr. Barham looked into the severity and duration of their symptoms and linked it to the different taste groups. The results were consistent with his retrospective study. 

The non-taster subjects were more likely to get infected, to get admitted to hospital once infected, and to have the severest symptoms among the different groups.  In fact, 85% of the subjects who were hospitalized with COVID-19 had been identified as non-tasters. The remaining 15% were from the taster group–and their average age was 74. As expected, older people had less favorable outcomes. Again, not one of those requiring hospital admission was in the supertaster group. Supertasters were only 5.6% of the COVID-19 subjects. As for the duration of symptoms, the non-tasters had severe symptoms for 23.7 days on average, tasters had moderate symptoms for 13.5 days, and finally, the supertasters had mild symptoms for only 5 days.

Even though the findings relating to T2Rs and COVID-19 are new and exciting, those who have been studying the relationship between T2Rs and upper respiratory infections were not surprised at the relationship. But the strength of the relationship is incredible. If you’d like to find out which taste group you are in, a simple, at-home test called Phenomune can give you the answer.

References

• Human Biology of Taste
• Neural responses to bitter compounds in rats
• Smallest bitter taste receptor (T2Rs) gene repertoire in carnivores
• The repertoire of bitter taste receptor genes in canids
• TAS2R38 bitter taste receptor and attainment of exceptional longevity
• Association Between TAS2R38 Gene Polymorphisms and Colorectal Cancer Risk: A Case-Control Study in Two Independent Populations of Caucasian Origin
• The emerging role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis
• What is a Supertaster?
• Henry P. Barham, M.D.
• Phenomune: Applying Science to Help People Proactively Improve Wellness
• Does phenotypic expression of bitter taste receptor T2R38 show association with COVID-19 severity?
• Association Between Bitter Taste Receptor Phenotype and Clinical Outcomes Among Patients With COVID-19
• How Do I Get Tested to See if I’m a Supertaster?
• Phenomune