Circadian Rhythm Disruption Aggravates DSS-Induced Colitis in Mice with Fecal Calprotectin as a Marker of Colitis Severity

• Published in: Digestive diseases and sciences Vol. 64; no. 11; pp. 3122 - 3133
• Main Authors: Amara, Joseph, Saliba, Youakim, Hajal, Joelle, Smayra, Viviane, Bakhos, Jules-Joel, Sayegh, Raymond, Fares, Nassim
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2019; Springer; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomarkers - chemistry; Biomarkers - metabolism; Circadian rhythm; Circadian Rhythm - physiology; Colitis; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Colon; Cytokines; Dextran; Dextran Sulfate - toxicity; Ethylenediaminetetraacetic acid; Feces; Feces - chemistry; Gastroenterology; Gastrointestinal diseases; Hepatology; Inflammation; Inflammatory bowel disease; Leukocyte L1 Antigen Complex - analysis; Leukocyte L1 Antigen Complex - metabolism; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Mice; Mice, Inbred C57BL; Oncology; Original Article; Permeability; Risk factors; Severity of Illness Index; Sulfates; Transplant Surgery; Fecal calprotectin; DSS-induced colitis; Inflammation; Circadian rhythm
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-019-05675-7

Background Inflammatory bowel disease (IBD) is a chronic immunologically mediated pathology that remains a major health burden. Circadian rhythm disruption leads to a deregulation in the immune system which is a major risk factor for IBD. Aims Since fecal calprotectin (FC) has been a useful tool for monitoring IBD, we aimed to evaluate the effect of circadian rhythm alteration on gut inflammation status and whether FC is associated with the severity of colitis. Methods C57BL/6J mice were exposed to circadian shifts for 3 months, and then colitis was induced by 2% dextran sulfate sodium (DSS). Colitis was evaluated according to clinical symptoms and histological scoring. Plasma and intestinal inflammatory and permeability markers as well as fecal and intestinal calprotectin were assessed. Results Circadian shifts aggravated DSS-induced colitis with increased diarrhea, flatulence, and fecal blood associated with decreased colon length. In addition, intestinal cryptic architecture was lost with the presence of increased inflammation, mucosal muscle thickening, and cryptic abscesses. Plasma tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and C-reactive protein upregulations were paralleled by the deterioration of intestinal permeability. Calprotectin expression and distribution increased in the intestines and feces of shifted animals, and levels highly correlated with the increases in intestinal inflammation and permeability. Conclusions Circadian rhythm disruption aggravates DSS-induced colitis, whereas fecal and intestinal calprotectin associates with the severity of disease. Calprotectin might be a useful marker and tool for assessing patients at risk of IBD due to lifestyles with disruptive sleep patterns.