title: The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions.
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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Vindigni
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Zisman
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, WA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Suskind
authors.affiliation: University of Washington School of Medicine, 1959 NE Pacific Street, Box 356424, Seattle, WA 98195-6424, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Damman
keywords: Crohn’s disease; barrier function; inflammatory bowel disease; leaky gut; microbiome