The gut as a hidden source of sepsis

From the initial hypothesis considering 30 years ago the gut as the "motor" of multiple organ failure (MOF) related to an induced hyperpermeability leading to bacterial translocation into the systemic circulation, the reality becomes significantly more complex. The gut contains three interplaying components - the epithelium, the microbiome, and the immune system - that have to cooperate to maintain two opposite function: adsorption of nutrients and maintenance of a barrier to prevent the crossing of intraluminal microbes or their products to avoid host response. Many critical illnesses are altering such a functional integrity that facilitate the growth of pathogens, their translocation toward blood or lymph, and the activation of the systemic inflammation with high risk of MOF. The gut becomes then the "hidden cause" of sepsis related to complex mechanisms. This review tries to give a comprehensive description of these mechanisms, focused on induced sepsis. Some new therapeutic strategies are discussed.