Altered peripheral CRY1 gene expression may contribute to both organic and functional gastrointestinal disease.

Abstract

Gastrointestinal conditions such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) are characterized by alterations in physiological and immune functions. Given the circadian clock influences gastrointestinal physiology and immunity, we hypothesized that the peripheral circadian clock is altered in these patients and might contribute to immune activation associated with IBD and IBS. To investigate this, RNA was extracted from whole blood obtained from control subjects (n = 29), IBD (n = 40 ulcerative colitis, n = 38 Crohn's disease) and IBS (n = 38) participants to investigate peripheral clock gene expression via quantitative PCR. A linear regression model was used to assess the impact of the time of blood collection on clock gene expression. Self-reported data regarding fatigue and sleep indices were compared between patients and control subjects. Gene expression analysis revealed variations in the peripheral circadian system between IBD, IBS and control subjects. The core clock gene CRY1 had higher relative expression in IBS (p = 0.031) and ulcerative colitis patients (p = 0.042) compared with control subjects. Patients with gastrointestinal disease demonstrated poorer quality sleep (IBS p < 0.001, UC p = 0.025 and CD p = 0.007) and more troublesome sleep (IBS p < 0.001, UC p = 0.002 and CD p = 0.009) compared with control subjects. These data suggest a role for CRY1 gene expression in patients experiencing fatigue and highlight a link between circadian dysregulation and the pathophysiology of intestinal disease.