Influence of sleep disruption on inflammatory bowel disease and changes in circadian rhythm genes

Abstract

According to clinical investigations, sleep disruption (SD) can influence the immune system and cause inflammatory bowel disease (IBD). However, the detailed effects of sleep on IBD development and progression have not been clarified. Here, we used dextran sulfate sodium (DSS) to induce colitis in mice, and then interfered with SD (day-time 8:00 a.m. to 5:00 p.m.) to explore the influence of sleep on colitis by analyzing colon length, mouse body weight, disease activity index (DAI) score, pathology detection, and infiltration of inflammatory cells with LCA immunohistochemistry analysis. Next, we detected the mRNA levels of circadian genes and related inflammatory factors, including Bmal1, CLOCK, Cry1, Cry2, Per1, Per2, Timeless, Rev-erbα, TNF-α, IL-6, and IFN-γ. Additionally, we conducted a sleep survey in IBD patients and collected colon lesion sites to detect the mRNA levels of those eight circadian genes and three inflammatory factors. We found that SD promoted the body weight decrease, increased inflammation as shown with pathological staining of the DSS animal model, and increased expression of the clock gene Cry2 in DSS-induced colitis mice. In IBD patients with active disease, the mRNA level of circadian genes Bmal1, Cry1, Cry2, and Rev-erbα in inflammatory tissues decreased significantly compared with non-inflammatory tissues.

Keywords

• Inflammatory bowel disease
• Sleep disruption
• Circadian genes