New role for taste receptors

Taste receptors for bitter substances are not only found on the tongue but also on cells outside the oral cavity. As a new study by the Leibniz Institute for Food Systems Biology at the Technical University of Munich now shows, extraoral bitter taste receptors could also serve as endogenous sensors for bile acids. This discovery suggests that, in addition to food components, endogenous substances may have influenced the evolution of bitter taste receptors. Furthermore, the study provides new approaches to explore the health effects of food constituents in which extraoral bitter taste receptors are involved.

As taste sensors, bitter taste receptors serve to detect and avoid potential toxins in food. Relatively recent findings also indicate that bitter taste receptors are also found on cells of the lung, brain, and gastrointestinal tract, and on blood and sperm cells. A fact that suggests further, less well-studied receptor functions in the body, especially since the human body also produces bitter substances itself.

Based on these findings, the question arises whether bitter taste receptors evolved primarily as taste receptors or rather as endogenous sensors interacting with endogenous bitter substances. The latter, of course, would require that concentrations of endogenous substances in the corresponding body fluids be sufficient to activate endogenous bitter taste receptors on extraoral tissues and cells.

Bile acids are endogenous bitter substances

Bile acids are a good example of endogenous bitter substances and are present in various body fluids. Therefore, a team led by Maik Behrens from the Leibniz Institute in Freising, Germany, investigated which of the approximately 25 human bitter taste receptor types respond to physiologically relevant bile acid concentrations. For this purpose, the team used an established cellular test system and combined functional experiments with molecular modeling approaches. The eight bile acids tested included primary, secondary, tertiary, and conjugated bile acids.

As the team shows, five bitter taste receptor types respond to the bile acids tested. “In this context, the measured activation thresholds of the receptors matched very well the bile acid concentrations reported for human body fluids in the literature,” says Florian Ziegler, a doctoral student at the Leibniz Institute who contributed significantly to the study. “Moreover, we were not only able to characterize the binding of bile acids to the bitter taste receptor TAS2R1 by modeling studies but even reproduced the differences of experimental activity data,” adds Antonella Di Pizio, who heads the Molecular Modeling group at the Leibniz Institute.

Bile acids activate extraoral bitter taste receptors

“Our results suggest that there is indeed a physiological relationship between bile acids and certain extraoral bitter taste receptors and that the latter act as endogenous sensors of bile acid levels. 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,” summarizes principal investigator Maik Behrens. However, further studies are urgently needed to clarify the exact biological functions of the extraoral receptors, the biologist continues. He adds: “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.”

Publication: Ziegler, F., Steuer, A., Di Pizio, A., and Behrens, M. (2023). Physiological Activation of Human and Mouse Bitter Taste Receptors by Bile Acids. Communications Biology 6, 612. 10.1038/s42003-023-04971-3. https://www.nature.com/articles/s42003-023-04971-3

More Information

Bile acids: Bile acids are produced in the liver and are derivatives of cholesterol. They play an important role in fat digestion. Bile acids tested included the primary bile acids cholic acid and chenodeoxycholic acid, the secondary bile acids lithocholic and deoxycholic acid, the tertiary bile acid ursodeoxycholic acid, as well as the conjugated bile acids taurolithocholic, glycocholic, and taurocholic acid.

Bitter taste receptors that respond to bile acids: The human bitter taste receptors TAS2R1, TAS2R4, TAS2R14, TAS2R39, and TAS2R46 responded to at least three of the bile acids tested. Of these, receptor TAS2R1 was the least selective, being stimulated by all eight bile acids. In addition, the receptor TAS2R4 was activated by six, the receptor TAS2R14 by five, and the receptors TAS2R39 and TAS2R46 by three each of the bile acids.

As recent findings show, relatively high mRNA levels of the bitter taste receptor TAS2R1 are found in late spermatids (a precursor of sperms) in the testis. 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. From this, they concluded that food intake leading to the release of bile acids in the small intestine could have positive effects on the growth of E. coli and thus on the digestive process.

Contact

Scientific Contacts:

PD Dr. Maik Behrens
Head of the research group Taste & Odor Systems Reception
Leibniz Institute for Food Systems Biology
at the Technical University of Munich (Leibniz-LSB@TUM)
Lise-Meitner-Str. 34
85354 Freising / Germany
Phone: +49 8161 71-2987
E-mail: m.behrens.leibniz-lsb(at)tum.de

Dr. Antonella Di Pizio
Head of the research group Molecular Modeling at the Leibniz-LSB@TUM
Phone: +49 8161 71-6516
E-mail: a.dipizio.leibniz-lsb(at)tum.de

Press Contact at the Leibniz-LSB@TUM:
Dr. Gisela Olias
Knowledge Transfer, Press and Public Relations
Phone: +49 8161 71-2980
E-mail: g.olias.leibniz-lsb(at)tum.de
www.leibniz-lsb.de

Information About the Institute:

The Leibniz Institute for Food Systems Biology at the Technical University of Munich (Leibniz-LSB@TUM) comprises a new, unique research profile at the interface of Food Chemistry & Biology, Chemosensors & Technology, and Bioinformatics & Machine Learning. As this profile has grown far beyond the previous core discipline of classical food chemistry, the institute spearheads the development of food systems biology. It aims to develop new approaches for the sustainable production of sufficient quantities of food whose biologically active effector molecule profiles are geared to health and nutritional needs, but also to the sensory preferences of consumers. To do so, the institute explores the complex networks of sensorically relevant effector molecules along the entire food production chain with a focus on making their effects systemically understandable and predictable in the long term.

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