Impact of the indigenous flora in animal models of shock and sepsis

Septicemia is currently the 10th leading cause of death in the United States, and shock and trauma patients are the source of much of the morbidity and mortality associated with septicemia. There is substantial evidence that the composition of the indigenous flora plays an important role in modulating outcome variables in animal models of shock and sepsis. Germ-free animals that lack an indigenous flora are not as susceptible to shock as their conventionally reared counterparts. And, in conventionally reared animals, the composition of the intestinal flora can also modulate outcome in shock and sepsis. For example, certain bacterial species/strains disseminate from the intestinal tract more easily than others, antibiotic-induced alterations of the flora can modulate the incidence of systemic spread, and a certain threshold number of intestinal bacteria facilitates extraintestinal dissemination. The composition of the intestinal flora can also affect intestinal permeability, the production of inflammatory mediators, and the responses of immune cells in extraintestinal sites. And, there is evidence that prior exposure to endotoxin, via either the oral or systemic route, can influence outcome in animals challenged with parenteral endotoxin, a widely used model of endotoxin shock. The general composition of intestinal flora of experimental animals can be characterized with relative ease. This knowledge can aid data interpretation, either to help explain irreproducible or expected results or to verify that observed differences are likely related to the dependent variable studied rather than the composition of the indigenous flora.