Our group has previously demonstrated that in critically ill patients, the lungs and other end-organs are enriched with gut-associated bacteria. This observation has re-ignited the "gut translocation hypothesis" of multi-organ failure: that in patients with shock, increased intestinal permeability results in dissemination of gut bacteria and bacterial products, contributing to the pathogenesis of multi-organ failure. In this talk, I will share recent observations exploring the mechanisms and significance of gut translocation in critical illness. I'll share translational findings from complementary mouse, pig, and human studies.