Nuclear receptor Nr1d1 links sleep deprivation to intestinal homeostasis via microbiota-derived taurine

作者：Zhaoyang Wang, Lili Zhou, Yaxin Zheng, Xiaolan Zhong, Rufei Huang, Wei Sun, Shuai Wang, Wanglin Li · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-07089-8 · 被引用次数：8 · 研究领域：Aldose Reductase and Taurine、Gut microbiota and health、Sleep and related disorders

BACKGROUND: Sleep deficiency significantly compromises human health, with the gut being particularly susceptible. However, the molecular mechanisms by which gut microbiota mediate sleep deprivation-induced intestinal dysfunction remain largely undefined. In this study, we employed a chronic sleep deprivation (CSD) mouse model to investigate the impact of sleep loss on intestinal integrity and microbial composition. METHODS: The CSD mouse model was established using the modified multiple platform (rotating rod) method. Colon histomorphology was assessed by hematoxylin and eosin (HE) staining. Expression levels of barrier proteins (Occludin, Claudin-1) and circadian regulators (Nr1d1, Bmal1) were evaluated via Western blot or immunohistochemistry (IHC). Gut microbiota composition and stability were analyzed by 16S rRNA gene sequencing, and the causal role of microbiota in CSD-induced barrier damage was assessed through fecal microbiota transplantation (FMT). RNA sequencing (RNA-seq) of intestinal epithelial tissues identified differentially expressed genes and enriched pathways. Untargeted metabolomics was employed to investigate key differential metabolites (Taurine). Additionally, taurine was supplemented in vivo to explore its efficacy and mechanism in alleviating intestinal barrier damage in CSD mice. RESULTS: CSD led to pronounced colon shortening and significant downregulation of the epithelial barrier proteins Occludin and Claudin-1, indicative of impaired intestinal bar...