Sleep fragmentation frequency is associated with distinct immune, microbial, and barrier-related profiles in DSS-induced colitis in mice.

Background: Sleep fragmentation is common in inflammatory bowel disease, but whether different fragmentation frequencies are associated with distinct biological responses during colitis remains unclear. This study examined endpoint-specific responses to low- and high-frequency sleep fragmentation in DSS-induced colitis in mice. Methods: Male C57BL/6 mice were assigned to Control, DSS, DSS with low-frequency sleep fragmentation (DSS+LSF), DSS with high-frequency sleep fragmentation (DSS+HSF), or high-frequency sleep fragmentation alone (HSF). Colitis was induced with 2% DSS for 7 days. Sleep fragmentation was applied for 12 h/day during the light phase at 60 sweeps/h for LSF or 240 sweeps/h for HSF. Clinical indices, histology, epithelial barrier-associated proteins, inflammatory and stress-related markers, colonic CD4 Results: Clinical and macroscopic indices varied across experimental groups, but corrected comparisons among DSS-treated groups were not significant. Plasma corticosterone was increased in both DSS+LSF and DSS+HSF, whereas MPO was higher in DSS+LSF than in DSS+HSF. Colonic Th2 proportions were higher in DSS+HSF than in DSS and DSS+LSF. Other histological, barrier-associated, inflammatory, and metabolic findings were primarily descriptive. Conclusions: Low- and high-frequency sleep fragmentation were associated with distinct, endpoint-specific response profiles during DSS-induced colitis rather than a simple linear increase in disease severity. These findings support frequency-associated, domain-specific responses and warrant further longitudinal and mechanistic investigation.