Sleep Deprivation Promotes Colorectal Cancer in Apc Min/+ Mice Associated with Modulation of Gut Microbiota and Related Metabolites

mice, a well-established CRC model, were subjected to SD using a modified multiple-platform method. Fecal samples were analyzed using 16S rRNA gene sequencing and untargeted metabolomics, and tumor burden, intestinal inflammation, and gut barrier integrity were assessed by hematoxylin and eosin staining, immunofluorescence, and Alcian blue-periodic acid-Schiff staining. Our results showed that SD significantly aggravated CRC progression, as evidenced by an increase in tumor number and severity, impaired intestinal barrier integrity, and enhanced intestinal inflammation. In parallel, SD markedly altered the gut microbiota composition, characterized by a pronounced reduction in beneficial bacteria such as Lactobacillus. Metabolomic profiling revealed significant metabolic alterations, with taurocholic acid (TCA) identified as a prominently elevated metabolite. Transcriptomic and functional analyses suggested that TCA may be involved in CRC progression through the activation of the MAPK/ERK signaling pathway. Collectively, these findings support a model in which SD contributes to CRC progression in association with alterations in the gut microbiota and related metabolites.