Sleep recovery alleviates impaired glucose tolerance induced by sleep fragmentation possibly through gut microbiota in mice

Sleep disturbance is increasingly common and has been linked to adverse metabolic outcomes. This study investigated whether sleep recovery (SR) mitigates the effects of chronic sleep fragmentation (SF) on glucose metabolism, with a focus on gut microbiota and inguinal white adipose tissue (iWAT) transcriptomics. Mice were subjected to 8 weeks of SF followed by SR. After 2 weeks of SR (SF 8w-SR 2w), glucose intolerance persisted, accompanied by significant alterations in gut microbiota composition and iWAT gene expression. Key hub genes (Ncapg, Cenpe, Ttk) and glucose metabolism-related genes (Lnpep, Pten, Apoe, Cebpb, Ido1, Ahsg) were identified. Bacterial genera were significantly altered and associated with glucose metabolism. After 8 weeks of SR (SF 8w-SR 8w), glucose tolerance was restored, although alterations in gut microbiota composition persisted. Notably, Rikenellaceae_RC9_gut_group and Defluviitaleaceae_UCG-011 remained persistently altered. These findings indicate that short-term SR is insufficient to reverse SF-induced glucose intolerance, which is associated with changes in the gut microbiota and iWAT transcriptome. Although prolonged SR improves glucose metabolism, persistent microbial alterations suggest a lasting impact of SF, underscoring the potential role of gut dysbiosis in metabolic dysfunction following sleep disturbances.