Circadian rhythms and gut microbiota Dysbiosis: emerging gut-brain axis pathways in insomnia pathophysiology and Therapeutics

Brain Behav Immun. 2026 Feb:132:106203. doi: 10.1016/j.bbi.2025.106203. Epub 2025 Nov 30.

Abstract

Insomnia, a widespread sleep disorder, significantly impacts mental and physical health. Emerging research highlights the crucial role of gut microbiota (GM) in modulating circadian rhythms (CR), which regulate sleep-wake cycles. This review explores the interplay between GM dysbiosis, CR disruptions, and insomnia, synthesizing findings from human and animal studies. GM dysbiosis is linked to reduced microbial diversity and altered abundance of key taxa, such as short-chain fatty acid-producing bacteria, which influence clock gene expression and hormonal rhythms. CR disruption exacerbates GM imbalances, forming a feedback loop that impairs sleep regulation through both central and peripheral pathways. We also examine the therapeutic potential of probiotics in restoring GM balance and synchronizing CR. Clinical trials suggest that specific probiotic strains improve sleep quality by modulating microbial metabolites and their downstream effects on the circadian system. However, inconsistencies in outcomes underscore the need for precision interventions. The review concludes by identifying gaps in the current literature, emphasizing the necessity of integrative approaches combining metagenomics and personalized medicine to optimize GM-targeted therapies. These insights pave the way for novel, safer, and more effective strategies to manage insomnia by addressing its biological underpinnings.

Keywords: Circadian rhythm; Gut microbiota; Insomnia; Probiotics.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / physiopathology
  • Brain-Gut Axis* / physiology
  • Circadian Rhythm* / physiology
  • Dysbiosis* / microbiology
  • Dysbiosis* / physiopathology
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Probiotics / therapeutic use
  • Sleep / physiology
  • Sleep Initiation and Maintenance Disorders* / microbiology
  • Sleep Initiation and Maintenance Disorders* / physiopathology
  • Sleep Initiation and Maintenance Disorders* / therapy