Abstract BACKGROUND Sleep and other physiological processes are regulated by the circadian clock system. The central clock in the suprachiasmatic nucleus responds to light cues and coordinates peripheral clocks throughout the body including the gastrointestinal tract and immune system. Changes in the circadian clock and melatonin have been associated with disease activity in ulcerative colitis (UC). This study aimed to determine whether circadian misalignment induced by simulated night shift work (NSW) affects the central clock, measured by dim-light melatonin onset (DLMO) and urinary melatonin, and triggers downstream effects on the peripheral clock, assessed by serum cytokine levels. METHODS 17 subjects, 7 UC and 10 Healthy Controls (HC), were recruited into the study. All UC subjects were clinically inactive (partial Mayo Score ≤ 1) and on stable medications with no flares for the last 3 months. After two weeks of a prescribed regular sleep schedule, subjects were kept in the circadian lab for 7 d with strict control of their light/dark cycle. Blood samples were collected every 1-2 hrs over a 24-hr period under two conditions: baseline with circadian alignment, and after 3 d of simulated NSW with circadian misalignment. Urine was collected during each condition for 24 hrs. Plasma melatonin was analyzed by SolidPhase, Inc. by RIA. Urinary 6-sulfatoxymelatonin was measured by ELISA. Serum cytokines were assayed using a Meso Scale Discovery multiplex immunoassay and cosinor analysis. RESULTS In HC, DLMO was 20:43 ± 00:31 at baseline had a phase delay to 23:03 ± 00:48 after NSW (p 0.01). In UC, DLMO was 20:27 ± 01:05 at baseline and had a phase delay to 22:39 ± 01:53 after NSW (p 0.01). There was not a significant difference in DLMO between HC and UC at baseline or after NSW (Figure 1). Urinary melatonin was significantly elevated during the dark period at baseline in HC and UC subjects, but did not change over 24 hours after NSW in UC (Figure 2). UC exhibited a significant change in circadian amplitude of TNF-α (p 0.05) after NSW; while HC demonstrated significant changes in circadian amplitude of regulatory cytokines IL-10 and IFN-γ in response to NSW over 24 hours (p 0.05). CONCLUSION Circadian misalignment by night shift work caused different impacts on the central clock (melatonin) and peripheral clock (cytokines) in UC compared to HC. This study highlights the importance of the circadian clock in UC, including the impact of shift work in UC which may be a significant risk factor for disease activity. Further in vivo and in vitro studies are ongoing to determine the mechanisms through which circadian misalignment impact gut barrier homeostasis and systemic inflammation in UC.
Weiss et al. (2026) studied this question.