Intestinal hyperpermeability: a gateway to multi-organ failure?

Abstract

In critically ill patients, disruption of intestinal epithelial cell function occurs due to exposure of the epithelium to toxic internal and external inflammatory stimuli, which are key factors that trigger sepsis and multi-organ dysfunction syndrome (MODS). A greater understanding of how trauma and gut failure lead to sepsis and progression to MODS is much needed. In this issue of the JCI, Armacki and colleagues identify mechanisms by which thirty-eight-negative kinase 1 (TNK1) promotes the progression from intestinal apoptosis and gut failure to bacterial translocation, sepsis, and MODS. Moreover, the results of this study suggest TNK1 as a potential therapeutic target to prevent sepsis and MODS.

Figure 1. Multi-organ dysfunction syndrome (MODS).

Upper left panel: There is a feedback from intestinal hyperpermeability to MODS that causes an acceleration of epithelial cell apoptosis. Intestinal hyperpermeability opens the gateway of biological protection, thereby allowing bacterial translocation, enhancing cytokine production, and ultimately inducing the systemic inflammatory response. The cascade of the MODS will lead to sepsis through opening of the gateway, via intestinal hyperpermeability facilitated by enteric dysfunction and then the transfer of the local injury information to the CNS. The upper right panel shows how the colon links with the CNS, and the lower right panel shows the details of the colon from mucosa to myenteric nerve plexus. IPAN, intrinsic primary afferent neuron.