Inside the belly of a fruit fly, researchers at the University of Basel have uncovered something that challenges what we thought we knew about how bodies work: a tiny plug-like blockage, which they named Reinger's knot, that forces newborn flies to sleep instead of eat—and reveals something profound about the conversation between gut and brain.
For more than a century, scientists puzzled over why fruit flies with a defective apterous gene died young, knowing only that the mutation prevented wings from developing properly. Prof. Anissa Kempf's team set out to solve the mystery, and what they found opens a window into one of biology's most intimate mysteries: how the gut talks to the brain and shapes behavior itself.
When healthy fruit flies hatch, they face a critical sequence: first, they must expel meconium, the metabolic waste accumulated before birth, and only then can they begin feeding independently. Flies with the apterous gene defect cannot complete this first step. Instead of developing the four rectal papillae that healthy flies grow—structures essential for water reabsorption—mutant flies develop a single, plug-like obstruction in the hindgut that completely blocks the intestine. As Cindy Reinger, the study's first author, explains, "In healthy flies, four so-called rectal papillae form during early development. These structures are essential for water reabsorption to minimize water loss. Instead of developing four normal papillae, the mutant flies form a plug-like structure in the hindgut that completely blocks the intestine."
What happens next is striking. Unable to pass their meconium, these flies become increasingly lethargic and withdrawn. They sleep far longer than normal—a behavior Reinger interprets not as laziness but as survival strategy. "We think that the flies sleep more in order to conserve energy and thus survive longer," she says. "While sleeping, flies also move their proboscis rhythmically, which may help stimulate gut motility. Perhaps this is a desperate attempt to get rid of the meconium." Most remarkably, these flies refuse to eat, even when food is available and they are hungry. Without the ability to clear their gut, something in their biology tells them to stop feeding altogether.
The research, published in Science Advances in 2026, suggests that gut function acts as a master switch for fundamental behaviors. The flies' symptoms—constipation, loss of appetite, lethargy, and eventual tissue damage—mirror intestinal obstruction in humans so closely that the findings may illuminate mechanisms behind digestive disorders in our own species. Because fruit flies and humans share many biological pathways, what researchers learn in the fly's tiny body can illuminate the human condition.
This work opens urgent new questions: How exactly does the intestine signal the brain to suppress hunger? What role does the gut play in regulating sleep itself? How does the body know when conditions are safe enough to begin eating? These aren't abstract questions. They speak to the growing recognition that the gut is far more than a processing plant for food—it is a communicator, a decision-maker, perhaps even a teacher to the brain above it. Understanding this conversation could reshape how we approach everything from feeding disorders to digestive disease.