The Hunger Code: How Nutrient Deficiency Rewrites Brain Genes

When the brain lacks certain essential nutrients called amino acids, its genes change how they function. In this study conducted on a fruit fly model, these alterations cause them to be more attracted to protein-rich foods, such as yeast and beneficial bacteria. The study shows that even simple organisms can "sense" the lack of nutrients and adjust their behavior to seek what they need, revealing how the brain and body work together to maintain nutritional balance.

Nutrition is one of the most fundamental factors for the survival of any organism. Among the various nutrients, essential amino acids, those that the body cannot produce on its own, are indispensable for protein formation, cell growth, and brain function.

When there is a shortage of these nutrients, the organism needs to find ways to compensate for the deficiency, adjusting its metabolism and feeding behavior. However, the biological mechanisms that convert nutritional needs into food-seeking behaviors are still poorly understood.

Seeking to understand this relationship between nutrition and behavior, researchers studied what happens in the brain of Drosophila melanogaster, the popular fruit fly, when these insects are deprived of essential amino acids. This model is widely used in biology because it has a well-characterized nervous system and allows for detailed genetic experiments.

The study aimed to investigate how the lack of individual essential amino acids alters gene expression in the heads of Drosophila and how these changes are reflected in adaptive behavioral responses, such as increased searching for protein sources.

The researchers also sought to identify which specific genes are involved in transforming this nutritional deficiency into feeding-directed behaviors, such as the exploration of yeast and gut bacteria.

The scientists subjected adult flies to diets lacking individual essential amino acids, such as isoleucine and methionine, for a controlled period. They then performed transcriptome analyses, that is, they examined all the genes expressed in the flies' heads, to detect which genes increased or decreased their activity in response to the deprivation of each amino acid.

This approach allowed them to distinguish specific genetic signatures associated with the lack of each nutrient, and common response patterns that reflect general mechanisms of adaptation to states of nutritional deficiency.

Furthermore, the researchers analyzed genes linked to odor and taste perception, since these senses guide the feeding behavior of Drosophila. Two genes stood out:

- Or92a, which encodes an olfactory receptor essential for detecting yeast (the fly's main natural source of protein);

- Ir76a, a gene involved in the attraction of beneficial gut bacteria, which help improve physiological fitness when there is a scarcity of nutrients.

The team observed that both genes were upregulated (i.e., had increased expression) during amino acid deprivation, indicating that the fly's brain adjusts its sensory systems to direct foraging behavior.

The analyses showed that, although each type of essential amino acid deprivation (such as isoleucine or methionine) induces distinct transcriptional signatures, there is also a common set of genes affected across all deprivations. This suggests that the Drosophila brain possesses universal mechanisms for responding to nutritional deficiency, complemented by specific adjustments depending on the missing amino acid.

In particular, increased Or92a activity causes flies to become more attracted to yeast, while the upregulation of Ir76a intensifies the search for and ingestion of commensal bacteria that can compensate for nutritional deficiencies.

These results indicate a form of coordinated adaptation between the nervous system and metabolism, in which nutritional deprivation is detected, translated into genetic alterations, and transformed into intelligent behavioral changes, an evolutionary strategy that improves the chances of survival.

The study reveals how changes in nutrient availability can reshape gene expression in the brain and, consequently, alter feeding behavior. Even simple organisms, such as flies, possess sophisticated molecular mechanisms to identify nutritional deficiencies and adjust their actions in search of specific foods that restore internal balance.

These findings broaden our understanding of how the brain and metabolism communicate, shedding light on fundamental principles of the neurobiology of hunger and nutrition, principles that may, in the future, help us understand how nutritional deficiencies affect behavior in mammals, including humans.

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Lack of single amino acids transcriptionally tunes sensory systems to enhance microbiota intake

Gili Ezra-Nevo, Sílvia F. Henriques, Daniel Münch, Ana Patrícia Francisco, Célia Baltazar, Ana Paula Elias, Bart Deplancke, and Carlos Ribeiro

Current Biology, October 27, 2025

DOI: 10.1016/j.cub.2025.09.062 

Abstract:

Adequate intake of dietary essential amino acids (eAAs) is vital for protein synthesis and metabolism. Any single eAA deprivation is sufficient to increase protein intake in Drosophila melanogaster. How such nutritional “needs” are transformed into behavioral “wants” remains poorly understood. We derived transcriptomes from the heads of flies deprived of individual eAAs to identify mechanisms by which this is achieved. While specific eAA deprivations have unique effects on gene expression, a large set of changes is shared across deprivations. Namely, we show that Or92a, which is essential for the exploitation of yeast, the main protein source for flies, is upregulated upon eAA deprivation. Additionally, Ir76a upregulation is crucial for feeding on commensal bacteria that ameliorate the fitness of eAA-deprived flies. Our work uncovers common and unique transcriptional changes induced by individual eAA deprivations in animals and reveals novel mechanisms underlying the organism’s behavioral and physiological adaptation to eAA challenges.