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Updated: Mar 18, 2026

Investigating Intestinal Barrier Breakdown in Living Organoids
Published on: March 26, 2020
The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite
Stephen M Vindigni1, Timothy L Zisman1, David L Suskind2
1Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA.
Abstract:
We discuss the tripartite pathophysiological circuit of inflammatory bowel disease (IBD), involving the intestinal microbiota, barrier function, and immune system. Dysfunction in each of these physiological components (dysbiosis, leaky gut, and inflammation) contributes in a mutually interdependent manner to IBD onset and exacerbation. Genetic and environmental risk factors lead to disruption of gut homeostasis: genetic risks predominantly affect the immune system, environmental risks predominantly affect the microbiota, and both affect barrier function. Multiple genetic and environmental 'hits' are likely necessary to establish and exacerbate disease. Most conventional IBD therapies currently target only one component of the pathophysiological circuit, inflammation; however, many patients with IBD do not respond to immune-modulating therapies. Hope lies in new classes of therapies that target the microbiota and barrier function.
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