Gut Microbiome and Host Defense Interactions during Critical Illness

Abstract

For many years it has been hypothesized that the gut has an important detrimental role in promoting systemic inflammation and infection in the critically ill. During stress and mucosal hypoxia, the mucosa is damaged and host defenses break down causing translocation of bacteria and bacterial toxins which are thought to contribute to the overwhelming inflammation associated with sepsis and multiorgan failure [1, 2]. New emerging data on the role of the microbiome have forced us to reassess the old ‘gut as motor of sepsis’ hypothesis. The gut microbiome consists of a diverse and vast population of microbes that has an important protective impact on immune effector functions during both health and disease (Fig. 1). It has become clear that the intestinal microbiome, consisting of more bacteria than the total number of cells in the human body, can be seen as an exteriorized organ that exerts numerous functions in the host response against infections [3, 4]. In addition to the more localized influence of the microbiome on the intestinal immune system, recent data show that the microbiome also plays a key role in systemic activation of the immune system contributing to the effective killing of invading pathogens [5]. The clinical relevance of these new insights is underscored by the notion that antibiotic treatment — which on any given day is received by almost three quarters of all patients on the intensive care unit (ICU) [6] — can largely deplete the microbiome. This review focuses on key aspects of the role of the intestinal microbiome in the immune response against pathogens and the importance of intestinal homeostasis for critically ill patients.