Scientists find gut-brain link that makes animals crave protein

The body needs more than calories to survive. It must get the right mix of nutrients, especially amino acids—the building blocks of protein that our bodies cannot make on their own. Scientists have now discovered how the gut and brain work together to detect when protein levels drop and push animals to find food that contains it.

A team led by Director SUH Seong-Bae of the Center for Microbiome-Body-Brain Physiology at the Institute for Basic Science (IBS) worked with scientists from Seoul National University and Ewha Womans University to map this hidden signaling network. Their findings were published in Science on May 21. The research shows that when protein is scarce, the gut rapidly changes feeding behavior and food preferences.

Scientists have long known that animals crave protein-rich foods when they lack protein. What remained unclear was exactly how the body sensed this shortage. The team discovered that the gut uses two separate but coordinated communication systems to alert the brain. The first pathway works through the nervous system and sends fast warnings that amino acids are missing. The second pathway moves more slowly through hormones in the bloodstream, helping maintain the drive to seek protein over time.

To understand this mechanism, researchers studied fruit flies, which scientists commonly use to investigate feeding behavior circuits in the brain. Using brain imaging, behavioral tests, and genetic experiments, they mapped the specific neural pathways involved. When flies lacked dietary protein, specialized intestinal cells released a peptide hormone called CNMa. This hormone activated nerve cells in the gut, which immediately sent signals to the brain through a direct neural connection. At the same time, CNMa also traveled through the bloodstream, reaching the brain gradually and reinforcing the desire to find amino acids.

"Our study shows that the gut is not simply a digestive organ, but an active sensory system that continuously monitors nutritional state and directly guides behavioral decisions," Director SUH Seong-Bae said. The newly identified system did not just make animals eat more overall. Instead, it specifically changed what they wanted to eat. Protein deficiency increased attraction to protein-related nutrients while reducing interest in sugar. CNMa signaling suppressed activity in sugar-sensitive brain cells called DH44 neurons, shifting feeding preferences away from carbohydrates and toward protein-rich foods.

Gut bacteria also played an important role in the process. Fruit flies lacking normal gut microbes showed much stronger activation of amino acid-seeking brain neurons. This suggests that the microbiome helps regulate how available nutrients are and influences feeding behavior. The researchers found evidence that the same basic mechanism exists in mammals too. Experiments in mice showed that animals deprived of protein developed a strong preference for essential amino acids, similar to fruit flies.

One surprising finding involved FGF21, a hormone scientists previously thought was central to protein appetite in mammals. Even mice lacking FGF21 still showed strong amino acid-seeking behavior. "This suggests that animals possess additional nutrient-sensing systems that scientists have not yet identified," the researchers said. The overall finding shows that animals do not simply become hungrier when nutrients are missing. Instead, the brain appears to selectively prioritize foods containing the nutrients the body specifically lacks.

The scientists believe this discovery could improve understanding of obesity, metabolic disease, and eating disorders. "Most current obesity and appetite-control drugs rely on gut hormone signaling, yet we still know relatively little about how naturally produced gut signals influence the brain and behavior," Director SUH Seong-Bae explained. "This study reveals fundamental principles of nutrient selection by the gut-brain axis and provides a foundation for future therapeutic strategies targeting metabolic and feeding disorders."