Scientists have discovered that the same receptors responsible for detecting bitter flavors on our tongues are also present and active on human skin. Their job is to detect bitterness, not as a flavor, but as a warning to the body, prompting cells to protect your skin from harm.

When exposed to bitter compounds, they spring into action, triggering a cascade of biological processes designed to expel potentially toxic substances.

These receptors, known as TAS2Rs, are not just confined to the mouth — they are scattered throughout the body, including in the skin and even in the lungs, gut, and brain, according to scientists in Japan.

A Bitter-Sensing Skin

The ability to perceive the bitter taste is thought to have evolved as a protective mechanism, signaling the presence of toxins in foods. When we bite bitter compounds, TAS2Rs respond by triggering neural pathways, leading to the characteristic sensation. In a way, the body is telling you, “spit it out! This may be dangerous to eat.”

But, over the past decade, scientists have discovered that TAS2Rs are not just on the tongue. They are also present in the lungs, gut, and even the brain.

In the skin, these receptors are in keratinocytes, the cells that make up the outermost layer of the epidermis. Keratinocytes are the body’s first line of defense against environmental hazards like pollutants, bacteria, and chemicals. But until now, the exact role of TAS2Rs in these cells was unclear.

We obviously can’t taste things just by touching them (how weird would that be?). But new research by scientists at Okayama University of Science in Japan, reveals that these receptors are not just passive sensors. They actively help skin cells expel harmful substances. 

A Molecular Pump for Toxins

The researchers focused on one particular bitter receptor, TAS2R38, known for its role in detecting compounds like phenylthiocarbamide (PTC). PTC is a chemical that tastes intensely bitter to some people but can be flavorless to others. They found that when TAS2R38 was activated by PTC or other bitter compounds, it set off a chain reaction inside the cell.

First, the receptor activated a protein called Gα12/13, which in turn triggered a series of molecular signals involving RhoA, ROCK, and p38 MAP kinase. These signals ultimately led to the activation of NF-κB, a protein that acts as a master switch for many cellular processes. One of NF-κB’s jobs is to ramp up the production of ABCB1, the toxin-flushing protein.

To test this complicated mechanism, the researchers exposed human skin cells in a petri dish to bitter compounds like PTC and saccharin. They found that the cells produced more ABCB1 and were better at expelling a fluorescent dye called rhodamine 123, which is known to be pumped out by ABCB1. When the researchers blocked ABCB1 with a drug called verapamil, the cells could no longer expel the dye as effectively.

This defense mechanism seems to be adaptive, getting better with prolonged exposure. When the researchers cultured skin cells with PTC or saccharin for over a month, the cells became even better at producing ABCB1 and expelling toxins. These “trained” cells were also more resistant to the toxic effects of diphenhydramine, a common antihistamine that can be harmful in high doses.

What does this mean for us?

This may mean that bitter compounds could be used to fortify the skin against environmental toxins. For example, they might be incorporated into skincare products to help protect against pollutants or chemicals that can damage the skin. Could artificially activating these receptors help treat skin conditions like eczema or psoriasis? It’s an exciting idea, but we need more research to understand how this could be applied in real-world settings.

So, surprisingly, bitter taste receptors don’t just have a role in taste. These receptors are like Swiss Army knives, performing different jobs depending on where they are.

While the findings are promising, many questions remain. Some compounds might be more effective at activating the receptors than others. This study only focused on a single receptor, TAS2R38, but there are 25 different TAS2Rs in humans. Each one has its own set of triggers and functions.

Another challenge is the variability in how people perceive bitter tastes. Genetic differences can make some people more sensitive to certain bitter compounds than others. What is true for the tongue may also be true for the skin — but we can’t be sure for now.

One thing is clear: the humble bitter taste receptor, is proving to be much more important than we thought. When you wrinkle your nose, your skin might be doing the same thing.

The findings appeared in the journal FASEB BioAdvances.