Not everything that tastes bitter is potentially harmful. But why? Study provides an explanation

A bitter taste is traditionally considered a warning sign of potentially toxic substances. But not all bitter substances are harmful. For example, some peptides and free amino acids taste bitter, even though they are non-toxic, nutritious and sometimes even vital for humans. A new study by the Leibniz Institute for Food Systems Biology at the Technical University of Munich now offers the first explanation for this seemingly paradoxical phenomenon.

In general, our sense of taste helps us to make food choices. Of the five basic tastes, sweet and umami indicate that a food is rich in energy and nutritious. Our sense of salt helps us to keep our electrolyte balance in equilibrium. Sour flavors can warn us of unripe or spoiled food, bitter ones of potentially toxic substances.

In view of numerous toxic plant substances such as strychnine from nux vomica or hydrogen cyanide from manioc, this seems to make sense. And it is also plausible that babies and toddlers in particular reject bitter foods. Even small amounts of such toxic substances are harmful to them.

Protein Fragments as Bitter as Gall

However, not everything that tastes bitter is dangerous, but can actually be nutritious. An interdisciplinary research team led by molecular biologist Maik Behrens has now investigated the reasons for this seemingly contradictory phenomenon for the first time.

Using an established cellular test system, the Leibniz team discovered that five of the approximately 25 human bitter taste receptor types react to free amino acids and peptides as well as to bile acids. The former are produced during the breakdown of proteins and are abundant in fermented foods such as cream cheese or protein shakes. Bile acids, on the other hand, play virtually no role as a food component, but fulfill their own functions in the body. They could therefore be considered as activators of endogenous bitter receptors, which are located on intestinal and blood cells, for example.

Explanation: Similar Structural Features

“Interestingly, our modeling experiments show that a certain bitter-tasting peptide can adopt a functionally active 3D shape similar to that of bile acids inside the receptor binding pocket. This coincidental similarity could explain why the same set of the bitter taste receptors react to both groups of substances,” explains bioinformatician Antonella Di Pizio.

First author Silvia Schäfer adds: “Our genetic analyses also show that the ability to recognize both bile acids and peptides is highly conserved in three of the bitter taste receptor types and can be traced back to amphibians. This again indicates that at least the recognition of one of the two substance groups is important across species.”

“Bile acids and bitter taste receptors existed millions of years before the typical bitter substances of today’s flowering plants and long before humans – in fish, for example. This supports the hypothesis that bitter taste receptors originally also regulated important physiological processes and not just warned against toxic substances,” explains principal investigator Maik Behrens. “Our findings provide new insights into the complex systems of taste perception and suggest that bitter receptors play additional, as yet unknown roles in human health that go beyond their function in food selection.”

Publication: Schaefer, S., Ziegler, F., Lang, T., Steuer, A., Di Pizio, A., and Behrens, M. (2024). Membrane-bound chemoreception of bitter bile acids and peptides is mediated by the same subset of bitter taste receptors. Cell Mol Life Sci 81, 217. 10.1007/s00018-024-05202-6.

Funding: Open Access funding made possible and organized by Project DEAL. This research was supported by the German Research Foundation (DFG) (BE 2091/7-1 to MB and PI 1672/3-1 to ADP)

Background Information:
Amino acids and peptides: Amino acids are found in all known living organisms. They are the building blocks of proteins and are released when the proteins are broken down. Essential amino acids cannot be produced by the organism itself and must therefore be taken in with food. If amino acids form chains of up to 100 amino acids, they are referred to as peptides. Longer polypeptide chains are also known as proteins.

Bile acids are produced in the liver and are derivatives of cholesterol. They play an important role in the digestion of dietary fats.

Bitter receptors: In humans, around 25 different types of taste receptors are responsible for the perception of bitter substances. These bitter taste receptors are not only found in the mouth, but also on cells in other organs and tissues. The diverse functions they fulfill there are the subject of numerous studies, including at the Leibniz Institute for Food Systems Biology at the Technical University of Munich. Various studies already indicate that bitter taste receptors in the airways help to ward off pathogens and accelerate the movement of cilia. They also suggest that endogenous bitter receptors of intestinal and blood cells support defense mechanisms or are involved in the regulation of metabolism.

Contacts:
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@tum.de

Silvia Schäfer
PhD student in the research group Taste & Odor Systems Reception
Tel.: +49 8161 71-2732
E-mail: s.schaefer.leibniz-lsb@tum.de

Assoc. Prof. 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@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@tum.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 a food systems biology. Its aim is 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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