Investigation of the Role of Stress in Inflammatory Bowel Disease Using Zebrafish as an Experimental Model.

摘要

Inflammatory bowel disease (IBD) is a chronic debilitating condition affecting 1.4 million Americans, young individuals in particular. Psychological stress and environmental factors such as diet, toxins and the microbiome contribute to disease precipitation and worsen its symptoms. War Veterans appear to be disproportionally affected by these factors. The medical management of IBD remains unsatisfactory and more than half of patients require some type of surgical intervention during their lifetime. The aim of our study was to establish and validate a zebrafish model of IBD, to be used for the development of novel treatments. The advantages of this model include its small size, housing requirements, short gestational period and easy genetic manipulations. We were able to induce chemical enterocolitis in adult zebrafish by intrarectal administration of TNBS. The following similarities with mouse experimental colitis and human IBD were identified: histological hallmarks including disruption of crypt architecture, infiltration by immune cells and mucosal edema; molecular mediators of inflammation such as TNFalpha, IL-1beta, IL-8 and IL-10; microbiome dependence; and disease alleviation in response to 5- aminosalicylic acid treatment. We will use this newly developed to accelerate progress in IBD therapeutics by focusing on evolutionary conserved pathways.