Extraoral bitter taste receptors could serve as additional digestive markers, study discovers

04 Jul 2023 --- Researchers from the Technical University of Munich have discovered that taste receptors for bitter substances are not only found on the tongue but also in cells outside the oral cavity. These extraoral bitter taste receptors could also serve as endogenous sensors for bile acids.

This discovery suggests that, besides food components, endogenous substances may have influenced the evolution of bitter taste receptors.

“Our results suggest that there is indeed a physiological relationship between bile acids and specific extraoral bitter taste receptors and that the latter act as endogenous sensors of bile acid levels,” says Maik Behrens, principal investigator of the study. 

“They also support the hypothesis that not only external factors such as bitter food constituents have influenced the evolution of bitter taste receptors, but also endogenous ones.” 

The study published in Nature provides new approaches to exploring the health effects of food constituents involving extraoral bitter taste receptors.

Bitter truths
As taste sensors, bitter taste receptors serve to detect and avoid potential toxins in food. Recent scientific findings show these receptors are also found in lung, brain and gastrointestinal tract cells. They are also present in blood and sperm cells.

Bile acids are produced in the liver and are derivatives of cholesterol. They play an essential role in fat digestion. 

In contrast, the bitter taste receptors TAS2R4, TAS2R14, TAS2R39 and TAS2R46 are expressed in different cell types of the small intestine and colon. Similarly, in other studies, researchers found that activation of the bitter taste receptor TAS2R4 by taurocholic acid increased the release of molecules that positively affect E. coli growth. An illustration of the extraoral taste receptors (Credit: Nature). 

From this, they concluded that food intake leading to the release of bile acids in the small intestine could positively affect the growth of E. coli and, therefore, the digestive process.

Delving into digestion
The researchers investigated which approximately 25 human bitter taste receptor types respond to physiologically relevant bile acid concentrations. 

The findings raise questions about whether bitter taste receptors evolved primarily as taste receptors or as endogenous sensors interacting with bitter endogenous substances. 

An established cellular test system and combined functional experiments with molecular modeling approaches were used. The eight bile acids tested included primary, secondary, tertiary and conjugated bile acids. Five bitter taste receptor types responded to the bile acids tested.

“Further studies are urgently needed to clarify the exact biological functions of the extraoral receptors. Gaining a deeper understanding of these functions could provide valuable insights into the potential health effects of food components when they interact with the extraoral bitter taste receptor-ligand systems,” says Behrens.

Meanwhile, Van Andel Institute (VAI) scientists are one step closer to developing new low-calorie alternative sweeteners that mimic sugar by activating sensory circuits in the brain and gut. The team has published the first-ever high-resolution images of TRPM5, a specialized protein concentrated in the taste buds, where it helps relay messages to and from cells.

By Inga de Jong