From plate to pillow: the role of food-derived bioactive compounds in sleep modulation and the potential of glia–neuron crosstalk

Sleep is a critical physiological process, yet the prevalence of sleep disorders is on the rise worldwide. Traditional pharmacological treatments often have limitations, prompting the search for alternative non-pharmacological interventions. Food-derived bioactive compounds (FBCs) have emerged as promising natural modulators for sleep improvement, offering vast potential for functional food development. This review systematically evaluates the nutritional significance of five major FBC categories: amino acids, polyphenols, fatty acids, bioactive peptides, and melatonin/indole derivatives. Furthermore, this review updates the mechanistic landscape by proposing a periphery-to-center axis that links peripheral signal perception (gut microbiota and peripheral circadian clocks), blood-brain barrier (BBB) translocation and/or BBB integrity modulation, and central integration through glia-neuron communication. Emerging evidence highlights that glial cells (astrocytes, microglia, and oligodendrocytes) are not passive support cells but active regulators of sleep homeostasis and circadian rhythms. FBCs may synchronize peripheral clocks, reinforce BBB tight junction function, and reprogram glial phenotypes to mitigate neuroinflammation and restore sleep architecture. It provides a solid scientific basis for developing safe, effective, and natural functional foods that promote sleep, offering novel insights into applying precision nutrition strategies to address sleep-related public health challenges.