Sleep, the Nervous System, and the Gut: An Ancient Alliance With Modern Consequences

Summary Across phylogeny, sleep interfaces with the intestine through conserved molecules and distributed circuits. In animals as simple as Hydra, sleep‑like quiescence is modulated by classic neuromodulators; in flies and mice, sleep loss provokes a gut‑centric oxidative crisis, rewires enteroendocrine output, accelerates whole‑body catabolism, and deranges epithelial renewal. A coherent picture is emerging: sleep’s essential biology is shared between brain and gut, with the enteric nervous system (ENS) and enteroendocrine cells (EEs) acting as both sensors and actuators. These insights outline a mechanistically precise, evolutionarily ancient brain–gut axis for sleep.