Eating isn’t just about getting enough calories. The body also needs to get the right balance of nutrients, especially essential amino acids, which are the building blocks of protein that the body cannot produce on its own.
Now, researchers have discovered a hidden communication system between the gut and brain that allows animals to detect when they’re low on protein and prompts them to seek out the nutrients they need.
A team led by SUH Seong-Bae, director of the Center for Microbiome, Body, and Brain Physiology at the Institute of Basic Science (IBS), collaborated with scientists from Seoul National University and Ewha Womans University to identify a previously unknown gut-brain signaling network that rapidly changes eating behavior when protein levels decline.
The research results were published in a magazine science May 21st.
How the gut detects protein deficiency
Protein is essential because it contains amino acids that animals cannot make on their own. Scientists have long known that animals tend to crave protein-rich foods when they lack protein, but it remained unclear exactly how the body senses this deficiency.
The researchers discovered that the intestine responds to protein deficiency using two separate but coordinated communication pathways.
One pathway works quickly through the nervous system to quickly alert the brain that essential amino acids are lacking. The second pathway works more slowly through hormones circulating in the body and helps maintain protein-seeking behavior over time.
To uncover this mechanism, the research team studied Drosophila melanogaster. Fruit flies are commonly used to investigate the neural circuits involved in feeding behavior. Scientists used brain imaging, behavioral tests, and genetic experiments to map the specific circuits involved.
When the flies’ diets lacked protein, specialized cells in their intestines released a peptide hormone called CNMa. This hormone activates enteric neurons connected to the gut, which quickly transmit signals to the brain via a direct nerve pathway from the gut to the brain.
At the same time, CNMa gradually reaches the brain through the bloodstream as a hormone, reinforcing the desire for essential amino acids.
“Our research shows that the intestine is not just a digestive organ, but an active sensory system that continuously monitors nutritional status and directly guides behavioral decisions,” said director SUH Seong-Bae.
Gut signals shift cravings away from sugar
The newly identified system doesn’t just make the animals eat more overall. Instead, they specifically changed what they wanted to eat.
Researchers found that protein deficiency increases interest in protein-related nutrients while decreasing interest in sugar.
CNMa signaling suppressed the activity of sugar-sensitive brain cells called DH44 neurons. As a result, dietary preferences have shifted from carbohydrates to protein-rich nutrients.
The study also showed that gut bacteria play an important role in the process. Drosophila melanogaster, which lacks normal gut microbes, showed stronger activation of amino acid-seeking brain neurons, suggesting that the microbiome helps regulate nutrient availability and feeding behavior.
Similar protein-seeking behavior is observed in mice.
Researchers found evidence that the same basic mechanism exists in mammals.
Experiments in mice showed that animals deprived of protein developed a strong preference for essential amino acids, similar to behavior seen in fruit flies.
One surprising discovery involved FGF21, a hormone previously thought to be central to mammalian protein appetite. Mice lacking FGF21 still showed strong amino acid-seeking behavior.
The researchers say this suggests that the animals have additional nutrient-sensing systems that scientists have not yet identified.
Overall, the findings show that animals don’t simply go hungry when they lack nutrients. Instead, the brain appears to selectively prioritize foods that contain nutrients that the body specifically lacks.
Potential impact on obesity and eating disorders
Scientists believe this discovery could help improve our understanding of obesity, metabolic diseases, and eating disorders.
“Most current obesity and appetite suppressants rely on gut hormone signaling, but we still know little about how naturally produced gut signals influence the brain and behavior,” said director SUH Seong-Bae. “This study reveals the fundamental principles of nutrient selection by the gut-brain axis and provides the basis for future therapeutic strategies targeting metabolic and eating disorders.”
