Intestinal obstruction impairs feeding and promotes sleep in Drosophila melanogaster.

At the onset of life, feeding must be initiated while developmental waste products-the meconium-need to be eliminated. Although these two fundamental physiological processes are interconnected, their mechanistic coupling remains poorly understood. Using Drosophila as a model system, we investigated the coordination of these processes. We show that meconium excretion starts shortly after eclosion and that feeding initiation begins only after partial meconium elimination. We identified a cis-regulatory element associated with the apterous gene that is required for proper hindgut development. Its disruption prevents meconium excretion and leads to intestinal obstruction. As a result, flies with a defective element avoid food and exhibit increased proboscis extension sleep. Experimental inhibition of excretion in freshly eclosed flies recapitulates these phenotypes, indicating that intestinal blockage is sufficient to impair feeding and alter sleep/wake states. The progression of phenotypes parallels hallmarks of mechanical gut obstruction in humans, suggesting that the observed effects may arise from broader physiological consequences of intestinal blockage. Our findings uncover a link between intestinal clearance, feeding, sleep, and survival, with potential implications for understanding similar processes across species.