Inverse Relationship Between Clock Gene Expression and Inflammatory Markers in Ulcerative Colitis Patients Undergoing Remission

Background: Changes in the expression of clock genes have been reported in inflammatory bowel disease (IBD) patients.

Aims: We aimed to investigate whether reduced inflammation restores clock gene expression to levels of healthy controls.

Methods: This was a prospective study. Participants completed questionnaires providing data on demographics, sleeping habits, and disease activity. Anthropometric parameters, C-reactive protein (CRP), and fecal calprotectin (Fcal) levels were collected. Peripheral blood samples were analyzed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1, PER2) expression. Patients with IBD were separated by diagnosis into ulcerative colitis (UC) and Crohn's disease (CD). Each diagnosis was further divided into active disease and disease under remission.

Results: Forty-nine patients with IBD and 19 healthy controls completed the study. BMAL1 and PER2 were significantly reduced in active patients with UC compared to patients with UC in remission. BMAL1, PER1, and PER2 were significantly reduced in patients with UC with CRP > 5 mg/dl. PER2, CRY1, and CRY2 were significantly reduced in patients with UC with Fcal > 250 mg/kg. Clock gene expression of patients with UC in remission was comparable to healthy controls. When all patients with IBD were analyzed, an overshoot in CRY1 expression was observed in patients in remission, patients with CRP < 5 mg/dl, and patients with Fcal < 250 mg/kg.

Conclusion: CRP and Fcal are inversely related to clock gene levels in patients with UC. CRY1 may play a role in counteracting the anti-inflammatory processes when remission is induced in patients with IBD.

Trial registration: ClinicalTrials.gov Identifier: NCT03662646.