Effect of critical illness on microbial translocation and gastrointestinal mucosa permeability

Abstract

It has been hypothesized that the barrier function of the gastrointestinal tract is deranged in patients with trauma, sepsis, or other critical illnesses. Derangements in intestinal barrier function might lead to bloodstream invasion by gut-derived microbes and/or activation of inflammatory cells in the submucosa of the intestine or within the liver. Activated immune cells are capable of releasing a number of inflammatory mediators, including eicosanoids and cytokines, which have been implicated in the pathogenesis of the multiple organ dysfunction syndrome (MODS). Thus, gut-barrier dysfunction might be primary factor leading to MODS in patients with critical illness. Two distinct forms of gut-barrier dysfunction have been described. The first, called translocation, appears to a transcellular process, whereby particulate antigens, including viable microbes, are transported across enterocytes into the submucosal compartment. The second is an increase in the paracellular permeability of the intestinal epithelium, which permits increased transmucosal absorption of water-soluble macromolecules. Pathological increases in both translocation and permeability occur in a number of animal models of critical illness. Moreover, a number of studies have documented that intestinal permeability is increased in humans with trauma, sepsis, burns, or other serious, acute medical problems. Nevertheless, convincing data to establish a causal link between gut-barrier dysfunction and organ failure in humans are lacking, and the importance of translocation and/or mucosal hyperpermeability on the development of MODS in patients remains to be elucidated.