A groundbreaking study from Duke University has revealed that the human gut harbors a natural appetite-regulating system, akin to the effects of weight-loss drugs like Ozempic, potentially offering a new approach to managing obesity without medication side effects.

Published in Nature, the research identifies a unique communication network in the colon involving specialized gut bacteria and cells that signal the brain to curb appetite. The study focuses on a gut bacterium called flagella, which releases a protein known as flagellin during digestion. This protein triggers the production of the PYY hormone, which activates a neurobiotic pathway—a direct link between the gut and the nervous system. This pathway informs the brain in real time when the body is full, helping to prevent overeating and excessive calorie intake.

In experiments with mice, researchers tested two groups: one with TLR5 receptors in the gut, which respond to the PYY hormone, and another without. After fasting overnight and receiving a dose of flagellin in the colon, mice with TLR5 receptors ate less the following day, while those lacking the receptors consumed more and gained significant weight. This pattern held for both male and female mice, suggesting the system’s broad relevance.

The findings indicate that flagellin and TLR5 receptors act as a natural “stop eating” mechanism. When large amounts of food are consumed, flagella releases higher levels of flagellin, intensifying the PYY signal to the brain to halt eating. Without this system, overeating becomes more likely, contributing to weight gain and obesity.

Lead researcher Diego Bohórquez, an associate professor of medicine and neurobiology, described the discovery as a “sixth sense” originating in the gut, comparable to sensory inputs like sight or taste. “This system allows the gut to sense microbial patterns in real time, guiding behaviors like eating,” Bohórquez explained. He believes the findings could help explain how microbes influence human behavior beyond immune responses.

While human studies are needed to confirm these results, the researchers propose that enhancing this gut-brain communication—through targeted diets, prebiotics, or probiotics—could support weight loss naturally. By mimicking the appetite-suppressing effects of GLP-1 drugs, this bacterial system offers a promising avenue for obesity management. The team aims to further explore how the gut’s microbial interactions shape not only eating habits but also mood and other behaviors, opening new frontiers in understanding the body’s hidden sensory networks.