Sleep as a Transdiagnostic Target in Psychiatry: Prebiotics, the Gut-Brain Axis, and the Gap Between Mechanistic Plausibility and Clinical Evidence.

Sleep disturbances are highly prevalent across psychiatric disorders and represent both a clinical feature and a potential transdiagnostic therapeutic target. Growing evidence suggests that the gut microbiota may contribute to sleep regulation through immune, metabolic, circadian, and neuroendocrine pathways. Prebiotics, defined as selectively utilized substrates that confer health benefits through modulation of host microorganisms, have received increasing attention as nutritional strategies capable of influencing the gut-brain axis. This narrative review summarizes preclinical and human evidence on prebiotic interventions in relation to sleep-related outcomes and psychiatric symptomatology, with particular attention to short-chain fatty acids, circadian regulation, inflammatory pathways, stress-related hypothalamic-pituitary-adrenal axis activity, and microbial metabolite signaling. Preclinical studies suggest that selected prebiotics may influence sleep architecture, stress resilience, neuroinflammation, and behavioral phenotypes, particularly under conditions of stress or sleep disruption, but translation to human populations remains preliminary. Available clinical studies are limited by small sample sizes, heterogeneous prebiotic formulations, variable doses and intervention durations, inconsistent microbiome methodologies, and frequent reliance on subjective sleep measures rather than polysomnography or actigraphy. Therefore, current evidence supports prebiotics as biologically plausible and generally well-tolerated adjunctive strategies, but not as established treatments for insomnia or psychiatric symptoms. Sleep may provide a clinically meaningful transdiagnostic framework for future nutritional psychiatry research, provided that adequately powered randomized controlled trials integrate objective sleep assessment, standardized microbiome and metabolomic profiling, and clinically relevant psychiatric outcomes.