The Gut-Brain Axis in Sleep Deprivation: Mechanisms, Dysbiosis, and Potential Therapeutic Avenues

Sleep is fundamental to metabolic regulation, cardiovascular health, immune balance, and cognitive performance. Emerging evidence indicates that sleep deprivation alters gut microbial communities and immune signaling, thereby influencing the gut-brain axis. This narrative review synthesized current findings on how sleep loss engages gut-brain pathways and evaluated therapeutic avenues linked to specific mechanisms, drawing on peer-reviewed human and animal studies and prioritizing sleep- and brain-relevant outcomes. Evidence converged on three mechanistic pillars: (1) circadian and microbial misalignment, which disrupts diurnal microbiome dynamics; (2) inflammatory and barrier dysfunction loops that increase permeability and immune activation; and (3) altered neurotransmitter and metabolite signaling, including shifts in tryptophan pathways and reduced short-chain fatty acid production, with downstream effects on neuroinflammation and plasticity. Human data supported associations between sleep loss, poor sleep quality, and impaired cognition. However, causal inference was limited by small sample sizes, study heterogeneity, and mixed endpoints. Interventions such as probiotics, prebiotics, postbiotics, synbiotics, diet-based short-chain fatty acid strategies, and chronobiotics are biologically plausible, yet they are supported mainly by small trials or preclinical models. Fecal microbiota transplantation shows exploratory, yet faces significant safety, standardization, and regulatory challenges. Collectively, the evidence indicated that sleep deprivation disrupts gut microbiota composition and gut-brain signaling, with consequences for neuroinflammation, neurotransmitter balance, and cognition. This review highlighted the consequent need for standardized endpoints, strain-resolved microbiome analyses, and well-powered randomized controlled trials.