Interplay between gut microbiota and insomnia: latest research advances based on the gut-brain axis

Abstract Objective Based on the bidirectional communication mechanism of the gut-brain axis, this study aims to systematically elucidate the interactive pathways between gut microbiota and insomnia, review the research progress of microbiota-targeted interventions for insomnia, and analyze the current bottlenecks in clinical translation, so as to provide theoretical basis and novel insights for the precise prevention and treatment of chronic insomnia. Methods Relevant articles on gut microbiota and insomnia published between January 2021 to January 2026 were retrieved from PubMed/Embase databases. Data from case-control studies, randomized controlled trials, animal experiments, and Mendelian randomization studies were integrated. The associated mechanisms, intervention strategies, and existing problems between gut dysbiosis and insomnia were summarized from three dimensions: neural pathways, metabolites, and immune inflammation. Results Gut microbiota and insomnia form a vicious cycle via the gut-brain axis. Gut dysbiosis disrupts sleep-wake cycle and circadian rhythm through vagal nerve transmission, disordered short-chain fatty acids/tryptophan metabolism, and IL-6/TNF-α-mediated neuroinflammation. Insomnia patients are characterized by reduced microbial diversity, decreased short-chain fatty acid-producing bacteria, and enrichment of pathogenic bacteria. Interventions such as probiotics, prebiotics, and fecal microbiota transplantation can improve sleep parameters, but are limited by inconsistent efficacy, unclear long-term safety, and non-standardized regimens. Individualized multi-omics precise regulation is the key to breakthrough. Conclusion Gut microbiota serves as a crucial target for insomnia prevention and treatment, which modulates sleep processes through multiple pathways of the gut-brain axis. Future research should improve long-term safety evaluation, establish standardized diagnosis and treatment systems, and promote individualized microbiota interventions based on multi-omics technologies, facilitating the translation of microecological strategies from basic research to precise clinical application in insomnia.