Gut Microbiome-Sleep Crosstalk: Mechanistic Pathways, Dysbiosis Signatures, and Microbiome-Based Interventions

This review examines the bidirectional relationship between sleep regulation and the gut microbiome within the gut-brain axis, with particular attention to mechanistic pathways, disorder-associated dysbiosis patterns, and microbiome-targeted interventions in insomnia, obstructive sleep apnea, circadian disruption, and sleep loss-related states.

We critically synthesized evidence from both human and preclinical studies, focusing on microbial metabolites, neuroimmune and neuroendocrine signaling, circadian regulation, and intervention-based approaches. Rather than only summarizing individual studies, we aimed to distinguish associative human findings from mechanistic evidence derived mainly from animal models.

Current evidence supports a bidirectional link between sleep and the gut microbiome. Microbiota-derived metabolites, particularly short-chain fatty acids, tryptophan-related metabolites, and gamma-aminobutyric acid, appear to influence sleep homeostasis through effects on intestinal barrier integrity, inflammatory tone, stress-axis regulation, and central signaling pathways. Across sleep disorders, recurrent microbial patterns include reduced abundance of potentially beneficial taxa such as Bifidobacterium and Faecalibacterium and enrichment of pro-inflammatory or stress-associated taxa, although these signatures are not yet fully consistent across cohorts or disorders. In humans, most data remain observational and support association rather than causation, whereas stronger mechanistic support comes from experimental models of sleep deprivation, intermittent hypoxia, and microbiota transfer. Early intervention studies suggest that selected probiotics, prebiotics, dietary modulation, and related microbiome-directed strategies may improve sleep-related outcomes, but the magnitude and reproducibility of these effects remain uncertain.

The gut microbiome represents a promising mechanistic and therapeutic target in sleep medicine, but clinical translation is still constrained by heterogeneity in microbiome profiling, sleep phenotyping, intervention design, and strain-specific effects. Future work should prioritize longitudinal human studies, standardized outcome measures, and mechanistically informed trials capable of identifying clinically actionable and biologically credible microbiome signatures.