There are times when you suddenly crave meat. It may look like a matter of taste, but inside the body, a precise signaling system may already be detecting a lack of nutrients and working to replenish them. A recent study found that the gut detects protein deficiency and sends signals to the brain to steer you to selectively eat the nutrients you need.
The Ministry of Science and ICT said that the research team led by Seo Seong-bae, Director General of the Institute for Basic Science (IBS) Microbiome–Body–Brain Physiology Research Center, together with joint researchers at Seoul National University and Ewha Womans University, identified the principles by which the gut and brain regulate feeding behavior under protein-deficient conditions. The findings were published in the journal "Science" on the 22nd.
Protein, along with carbohydrates and fat, is one of the three major nutrients that make up and maintain our bodies. Protein is made up of multiple amino acids consolidated together, and among them, essential amino acids cannot be produced sufficiently in the body and 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 bodies recognize a shortage of essential amino acids and how they change behavior to find the necessary foods. Previous research has shown that the gut senses a variety of information—nutritional status in the body, food components, gut microbes, pathogens—and influences whole-body metabolism. For this reason, the gut is called the "second brain," and the consolidation system through which the gut and brain exchange information is called the "gut–brain axis."
On the 21st at a briefing on the research findings held in Gwanghwamun, Seoul, Director General Seo said, "Many anti-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."
Earlier, in 2021, the team traced this process step by step through fruit fly experiments. They found that when essential amino acids were deficient, expression of a peptide hormone called "CNMa" increased in intestinal epithelial cells of the flies. Peptide hormones are signaling molecules in the form of relatively small protein fragments that transmit information between cells. CNMa acted as a key signal that regulates essential amino acid intake behavior under protein-deficient conditions. The results were published in the journal "Nature."
In this study, the researchers confirmed that CNMa signaling is transmitted through a dual system of the gut–brain axis. When intestinal epithelial cells sense nutrient deficiency, a signal is first sent to the brain via the neural network consolidated with the gut within 30 seconds to 1 minute. As a result, it helps immediately respond to the deficiency by increasing essential amino acid intake. Next, CNMa hormone secreted from the gut travels through the circulatory system and more slowly reaches the brain to sustain protein-preference behavior for a certain period. Simply put, the neural pathway is a fast alert, while the hormonal pathway is a mechanism for sustained adjustment.
In this process, specific neural circuits in the brain also changed. The team confirmed that CNMa signaling activates enteric neurons and neurons in the ellipsoid body region of the brain to promote essential amino acid intake. At the same time, CNMa reduced the activity of DH44 neurons that 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 explained, "When protein is lacking, it does not mean the body simply eats more of any food, but rather that it reduces sugar intake and adjusts eating direction to choose feed that contains essential amino acids."
The researchers also confirmed that this phenomenon does not occur only in fruit flies. In mouse experiments, protein deficiency likewise induced behavior seeking essential amino acids, and the same gut–brain axis system operated. Notably, this response persisted even in the absence of the liver-derived hormone FGF21, previously known to be involved in protein restriction and changes in energy metabolism. This suggests the possibility of another nutrient selection control 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 basis for future research on treatments for obesity, metabolic diseases, and eating behavior disorders."
Separately, Choi Hyeong-jin, a professor in the Department of Anatomy at the Seoul National University College of Medicine and the Department of Brain and Cognitive Sciences in the College of Natural Sciences, who was not involved in the study, said, "This discovery directly connects to medical and nutritional applications for a more balanced, healthy diet," and added, "I expect it will offer a new breakthrough in various modern diseases and clinical situations where insufficient protein intake threatens health, including sarcopenia."
References
Science (2026), DOI: https://doi.org/10.1126/science.adv3355