The sense of taste gives us clues as to whether a food is wholesome or harmful. Researchers have now discovered a new receptor in fruit flies that enables them to taste alkaline food. Since this is harmful to the animals, they usually avoid it after trying it for the first time. On the other hand, individuals in whom the researchers switched off the newly discovered taste receptor could no longer distinguish between foods with a neutral and alkaline pH value and showed no preference when it came to eating them. According to the researchers, it is conceivable that other animals, and perhaps even humans, may also have previously undiscovered alkaline taste receptors.
Before we consume a potential food, we perceive how it tastes through the taste buds on our tongue combined with the olfactory cells in the nose. This sensory impression provides us with important information about whether there is an edible food in our mouth or a toxic substance that we should spit out again quickly. Similar to humans, fruit flies (Drosophila melanogaster) have been shown to taste sweet, salty, bitter and sour. However, the question of whether living beings can perceive a high pH value via their sense of taste in addition to a sour taste, which indicates a low pH value, has long been controversial.
Evidence from early studies
"In the 1940s, studies on human subjects found that the tip of the tongue, which is enriched with taste buds, is more sensitive to the basic substance sodium hydroxide (NaOH) than the middle part of the tongue, which is devoid of taste buds," explains one team around Tingwei Mi from the Monell Chemical Senses Center in Philadelphia. "This indicates that alkaline solutions can have taste properties." Researchers also found that insects such as beetles avoid alkaline food. However, it remained unclear whether this behavior was based on an independent perception of taste.
"Since these early studies, little mechanistic research has been done to unravel the molecular and cellular basis of alkaline taste perception," say Mi and his colleagues. With extensive experiments on fruit flies, they have now proven that they actually have a sense of taste for alkaline substances. "We have isolated a gene in flies that regulates the taste response to strong alkalinity, which we have named alkaliphile (Alka)," the authors report. "Our molecular genetic studies found that Alka is both necessary and sufficient to avoid highly alkaline foods."
Newly discovered receptor shapes taste perception
The gene, which is expressed in taste receptor neurons in fruit flies, encodes a previously unknown ion channel that is directly activated by the hydroxide ion OH-, which characterizes all bases. When OH ions bind to the channel, it opens, allowing negatively charged chloride ions to flow out of the cell, depolarizing the membrane and propagating the signal. "Our work shows that chloride channels, which have long been overlooked, have crucial functions in taste signaling to the brain," says Mi's colleague Yali Zhang.
The team used various experiments to test exactly how the newly discovered receptor affects the taste perception of the fruit flies. In the first step, they had wild-type fruit flies choose between two types of food: a drop of sugar water, and a drop that contained the same amount of sugar, but with the addition of a small amount of sodium hydroxide. "The fruit flies strongly preferred the neutral sugar water and avoided the alkaline one," the researchers said. In the next step, they switched off the alka gene in some fruit flies through genetic modification. These animals lost their aversion to basic food, so apparently they could no longer perceive the high pH value.
Also in other species?
Using optogenetic methods, the researchers also directly manipulated the taste perception in some individuals. To do this, they genetically modified the animals in such a way that the nerve cells, which are normally activated by the alka receptor, could be controlled by exposure to light. If the researchers now ensured that the nerve cells are not activated, the flies also ate alkaline food. If, on the other hand, the researchers activated the corresponding nerve cells and artificially gave the flies an alkaline taste impression, the individuals also avoided neutral sugar water. "So the alkaline taste can have a big impact on what the flies want to eat," Zhang says.
From a biological point of view, this mechanism makes sense: fruit flies that regularly eat alkaline food have a shorter lifespan. Taste perception and aversion are therefore vital for them. Food with too high a pH value is also harmful to other living beings, including us humans. "The detection of an alkaline pH value is important for the food selection of many different species," the research team writes. It is therefore plausible that the corresponding receptors are not only found in fruit flies. "Our work provides a conceptual basis to study the neural mechanisms underlying alkaline taste sensations in other animals," the team said.
Source: Tingwei Mi (Monell Chemical Senses Center, Philadelphia, USA) et al., Nature Metabolism, doi: 10.1038/s42255-023-00765-3