There are times when you suddenly crave meat. It may look like a matter of taste, but inside the body, a sophisticated signaling system may already be detecting a nutrient shortfall and working to fill it. A recent study found that the gut detects a protein deficiency and sends signals to the brain, prompting people to selectively eat the nutrients they need.
The Ministry of Science and ICT said the team led by Seo Seong-bae, Director General of the Institute for Basic Science (IBS) Center for Microbiome–Gut–Brain Physiology, together with joint researchers at Seoul National University and Ewha Womans University, identified how the gut and brain regulate feeding behavior under protein shortage. The findings were published on the 22nd in the journal Science.
Protein, along with carbohydrates and fat, is one of the three major nutrients that make up and maintain our body. Protein is made up of multiple amino acids linked together, and among them, essential amino acids cannot be produced sufficiently in the body and therefore must be obtained from food. A lack of essential amino acids can affect growth, muscle maintenance, immune function, and metabolic regulation.
The researchers focused on how our body recognizes a shortage of essential amino acids and how it changes behavior to seek the necessary foods. Previous research has shown that the gut senses a wide range of information—nutritional status, food components, gut microbes, and pathogens—and influences whole-body metabolism. For this reason, the gut is called the "second brain," and the communication network through which the gut and brain exchange information is called the "gut–brain axis."
At a briefing on research outcomes held in Gwanghwamun, Seoul, on the 21st, Director General Seo said, "Many obesity and appetite-control drugs use gut hormone signals, but how naturally secreted gut hormones affect the brain and behavior has not been sufficiently studied."
In 2021, the team traced this process step by step in fruit flies. They found that when essential amino acids were deficient, expression of a peptide hormone called "CNMa" increased in the intestinal epithelial cells of fruit flies. Peptide hormones are relatively small, protein-fragment signaling molecules that transmit information between cells. CNMa acted as a key signal controlling essential amino acid intake behavior under protein deficiency. The results were published in the journal Nature.
In this study, the team confirmed that CNMa signaling is transmitted through a dual system of the gut–brain axis. When intestinal epithelial cells sense nutrient deficiency, a signal first reaches the brain within 30 seconds to 1 minute through the neural network connected to the gut. As a result, the body responds immediately to deficiency by helping increase essential amino acid intake. Then, CNMa secreted from the gut travels through the circulatory system and more slowly reaches the brain to sustain protein-preference behavior for a certain period. Put simply, the neural pathway is a rapid alert, while the hormonal pathway is a sustained tuning mechanism.
During this process, specific neural circuits in the brain also changed. The team confirmed that CNMa signaling activates neurons in the gut and in the brain's ellipsoid body to promote essential amino acid intake. At the same time, CNMa reduced the activity of DH44 neurons, which promote sugar intake. DH44 neurons are known in fruit flies to be neurons related to the intake of carbohydrates such as sugar.
Director General Seo said, "When protein is lacking, it does not mean the body simply eats more of any food; it adjusts the direction of eating to reduce sugar intake and choose feed that contains essential amino acids."
The researchers also confirmed that this phenomenon is not limited to fruit flies. In mouse experiments, protein deficiency likewise prompted behavior to seek essential amino acids, and the same gut–brain axis system operated. Notably, this response persisted even in the absence of FGF21, a liver-derived hormone previously known to be involved in protein restriction and changes in energy metabolism. This suggests the possibility of another nutrient-selection regulatory pathway that operates independently of FGF21.
Director General Seo said, "This study reveals how the gut and brain recognize lacking nutrients and link them to selective feeding behavior," adding, "It could provide an important foundation for future research into treatments for obesity, metabolic diseases, and eating behavior disorders."
Separately, Choi Hyeong-jin, a professor in the Department of Anatomy at Seoul National University College of Medicine and the Department of Brain and Cognitive Sciences in the College of Natural Sciences, who did not participate in the study, said, "This discovery directly connects to medical and nutritional applications for a more balanced, healthy diet," adding, "It is expected to offer a new breakthrough for various modern diseases and clinical situations in which insufficient protein intake threatens health, including sarcopenia."
References
Science (2026), DOI: https://doi.org/10.1126/science.adv3355