Gut-autonomic-brain loops in sleep regulation: From mechanisms to clinical implications.

Sleep is a fundamental physiological process closely linked to autonomic homeostasis. Rather than being governed by a localized neural switch, sleep-wake regulation depends on coordination between central circuits and peripheral physiology. The gastrointestinal tract is a major interface where this integration is evident. Ascending visceral signals can influence brain circuits involved in arousal and sleep, while sleep disruption can feed back onto the gut through descending autonomic pathways, altering motility, secretion, immune function, barrier integrity, and the intestinal environment. Here, we propose Gut-Autonomic-Brain Loops (GABLs) as a framework in which gut-derived microbial, immune, and metabolic cues reach sleep-relevant circuits through region- and stimulus-dependent vagal and spinal visceral afferents, while descending sympathetic and parasympathetic outputs feed back to shape gut physiology and the intestinal microenvironment. We outline the anatomical substrates of these loops, summarize autonomic dynamics across sleep and sleep disorders, and review evidence linking gut-derived signals to brain function and behavior through autonomic and interoceptive pathways. By specifying autonomic routes linking gut physiology to sleep-related brain function, this framework may help guide mechanistic studies and phenotype-informed translational research.