Statin-induced gut dysbiosis and sleep disturbances: Mechanistic insights into microbiota–brain–circadian interactions and chronotherapeutic implications

Statins are widely prescribed lipid-lowering agents with well-established efficacy in reducing cardiovascular morbidity and mortality. However, accumulating clinical and experimental evidence suggests that statin therapy may be associated with sleep disturbances, including insomnia, altered sleep architecture, vivid dreams, and reduced sleep quality. Emerging insights implicate the gut microbiota as a key regulator of host circadian rhythms and sleep homeostasis through interconnected pathways involving the tryptophan-serotonin-melatonin axis, short-chain fatty acid (SCFA) production, bile acid signaling, and immune-mediated neuroinflammation. Statins have been shown to modulate gut microbial composition, often reducing SCFA producing taxa and altering bile acid pools, which in turn may disrupt neurochemical signaling and circadian regulation. These microbiota-driven perturbations may contribute to central nervous system effects that underlie sleep-related adverse outcomes. This review integrates current mechanistic and clinical evidence linking statin-induced gut dysbiosis with sleep disturbances, highlighting the role of microbiome-host interactions in mediating off-target drug effects. It further examines implications for vulnerable populations, including shift workers, and discusses the potential of chronotherapy in optimizing statin administration. Finally, microbiota targeted interventions, such as probiotics, prebiotics, and dietary modulation, are proposed as promising strategies to mitigate these adverse effects. A deeper understanding of these interactions may enable personalized therapeutic approaches to enhance both cardiovascular outcomes and sleep health.