(IMAGE)
Caption
Schematic representation of sleep-microbiome interactions through the microbiota-gut-brain axis. Signals originating from the gut microbiome influence the sleep-wake cycle by modulating the flip-flop switch that governs these states. Sleep-promoting signals, such as butyrate, GABA, and melatonin, are received by sleep-related nuclei, while wakefulness-related signals, including 5-HT, orexin (ORX), and histamine (His), are detected by the sleep-related nuclei. The microbiota-gut-brain axis regulates sleep and wakefulness via three key pathways: Immune pathways, gut-derived immune factors are transmitted via the bloodstream and vagal afferents to modulate immune responses and microglial activation, affecting sleep regulation; Neural pathways, where gut microbes and their metabolites impact the enteric nervous system (ENS) and interact with afferent vagal pathways to influence sleep-related brain regions and circuits. Besides, the gut microbiota and their metabolites are also able to send signals to sleep-related brain regions through hypothalamic-pituitary-adrenal (HPA) axis. Metabolic and endocrine pathways, gut-derived neurotransmitters, and metabolites, such as bile acids (BAs) and short-chain fatty acids (SCFAs), can influence sleep through systemic circulation. Additionally, stress-induced activation of the HPA axis can alter sleep and gut microbiota composition. The regulation of sleep by central and peripheral signals maintains a dynamic balance, with bidirectional interactions between sleep and gut microbiota supporting optimal function. GABA, γ -aminobutyric acid; MT, melatonin; His, histamine; 5-HT, 5-hydroxytryptamine; ORX, orexin; HPA, hypothalamic-pituitary-adrenal axis; ACTH, adrenocorticotrophic hormone; BAs, bile acids; SCFAs, short-chain fatty acids.
Credit
Lin Lu
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Credit must be given to the creator.
License
CC BY