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Abnormal colonization, gut-origin infections, and bacterial translocation are all signs of gut dysfunction that may be implicated in the pathogenesis of multiple organ dysfunction syndrome (MODS). This review summarizes and updates relevant experimental and clinical data that have attempted to correlate these phenomena with the development of MODS and to answer whether or not the gut is the ‘motor’ of MODS. The presented data suggest that, in some patients, gut dysfunction may precede the development of MODS. However, in most patients, this relationship is less obvious. The gut may still be one of the motors of MODS; however, it does not appear that this motor is fueled by the systemic spread of bacteria. Bacteria may play a role on a local gut-associated level in initiating and perpetuating the production of local inflammatory mediators that may produce distant organ injury.