Does the Circadian Clock Have a Role in the Pathogenesis of Inflammatory Bowel Disease (IBD)?

Yael Weintraub 1,5 Shlomi Cohen 1,5 Iris Dotan 2,5 Riva Tauman 3,5 Oren Froy 4
1Pediatric Gastroenterology Unit,, Dana-Dwek Children’s Hospital, Sourasky Tel-Aviv Medical Center,
2Division of Gastroenterology, Rabin Medical Center, Petah Tikva,
3Pediatric Sleep Center, Dana-Dwek Children’s Hospital, Sourasky Tel-Aviv Medical Center
4University Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Food and Environment,, The Hebrew University
5Sackler Faculty of Medicine,, Tel Aviv University, Tel Aviv, Israel.

Background: Sleep dysfunction modifies the immune system and has been implicated as a potential trigger of IBD flares. It also alters the synchrony among clock genes leading to disruption of overall circadian regulation. Specifically, in the intestine, it is manifested by increased gut cellular permeability. Our aim was to investigate intestinal and systemic clock gene expression in IBD patients.

Methods: Patients and controls were recruited upon diagnostic endoscopic evaluation. Peripheral blood and tissue samples were analyzed for clock genes (Clock, Bmal1, Cry1, Cry2, Per1 and Per2) expression.

Results: Of the 32 participants (age 8-25), 14 had newly diagnosed IBD and 18 were healthy controls. Age, gender, sleep questionnaire scores and time of endoscopy were not statistically different between the groups. C-reactive protein and fecal calprotectin were significantly higher in the IBD compared to the healthy controls (p<0.05), while albumin and haemoglobin were significantly lower. Clock gene expression in WBC was decreased in IBD patients compared with health controls (p<0.05). Similarly, the expression level of the aforementioned genes was lower in inflamed intestinal tissues (p<0.05). Interestingly, similar reduction in clock gene expression was seen even in healthy (non-inflamed) intestinal tissue from IBD patients (p<0.05).

Conclusions: Clock gene expression is reduced in both inflamed and non-inflamed intestinal tissue in patients with newly diagnosed IBD. Moreover, IBD patients show a systemic reduction in clock gene expression compared to controls. Our findings may lead to new therapeutic strategies as well as serve as diagnostic tools in IBD.

Yael Weintraub
Yael Weintraub
Dana Dwek Children's Hospital, Sourasky TLVMC








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