Sleep Fragmentation Alters Gut Microbiota and Intestinal Barrier-Related Gene Expression in Mice

Sleep fragmentation (SF) is associated with metabolic dysfunction, systemic inflammation, and altered gut homeostasis. However, its effects on the gut microbial composition and intestinal barrier remain unclear. This study assessed whether SF alters the gut microbiota and its association with intestinal barrier integrity and enteric nervous system (ENS)-related markers in mice. Fourteen 6-week-old male BALB/c mice were assigned to a home cage control (HC) or SF group. SF was induced for 8 weeks, with fecal samples and colon tissues collected for 16S ribosomal RNA gene sequencing and quantitative real-time polymerase chain reaction analyses. Although α-diversity did not differ significantly, β-diversity revealed distinct microbial community structures. The SF group exhibited enrichment of potentially dysbiotic taxa, including Bacteroides, Parasutterella, Sellimonas, Gordonibacter, Peptostreptococcaceae, and Enterococcaceae, whereas Oscillospira, Roseburia, Monoglobus, and Lachnoclostridium were more abundant in the HC group. SF significantly downregulated tight junction protein 1 and occludin, whereas claudin-1 and ENS-associated markers (glial fibrillary acidic protein and S100 calcium-binding protein beta) were unaltered. Interleukin-6 was downregulated, whereas tumor necrosis factor and interleukin-1 beta were unaltered. These findings indicate that SF is associated with altered gut microbial dysbiosis and intestinal barrier-related genes, with limited effects on ENS-associated markers under the present conditions.