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INTESTINAL CROSSTALK: A NEW PARADIGM FOR UNDERSTANDING THE GUT AS THE "MOTOR" OF CRITICAL ILLNESS

Clark, Jessica A.; Coopersmith, Craig M.

doi: 10.1097/shk.0b013e31805569df
Review Articles

For more than 20 years, the gut has been hypothesized to be the "motor" of multiple organ dysfunction syndrome. As critical care research has evolved, there have been multiple mechanisms by which the gastrointestinal tract has been proposed to drive systemic inflammation. Many of these disparate mechanisms have proved to be important in the origin and propagation of critical illness. However, this has led to an unusual situation where investigators describing the gut as a "motor" revving the systemic inflammatory response syndrome are frequently describing wholly different processes to support their claim (i.e., increased apoptosis, altered tight junctions, translocation, cytokine production, crosstalk with commensal bacteria, etc). The purpose of this review is to present a unifying theory as to how the gut drives critical illness. Although the gastrointestinal tract is frequently described simply as "the gut," it is actually made up of (1) an epithelium; (2) a diverse and robust immune arm, which contains most of the immune cells in the body; and (3) the commensal bacteria, which contain more cells than are present in the entire host organism. We propose that the intestinal epithelium, the intestinal immune system, and the intestine's endogenous bacteria all play vital roles driving multiple organ dysfunction syndrome, and the complex crosstalk between these three interrelated portions of the gastrointestinal tract is what cumulatively makes the gut a "motor" of critical illness.

Department of Surgery, Washington University School of Medicine, St. Louis, Missouri

Received 12 Jan 2007; first review completed 23 Jan 2007; accepted in final form 1 Mar 2007

Address reprint requests to Craig M. Coopersmith, M.D., Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St. Louis, MO 63110. E-mail: coopersmithc@wustl.edu.

This study was supported by funding from National Institutes of Health (grant nos. GM072808-01 and GM66202-01).

©2007The Shock Society