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The pathobiome represents a potential therapeutic target in the management of critical illness whereby restoration of a healthier microbiome may directly alter the host inflammatory response, which could lead to improved patient outcomes. The gut microbiome is dramatically altered in the ICU. In light of constant crosstalk between the microbiome and the host immune system, the pathobiome may play a key mechanistic role in driving a maladaptive response in critically ill patients. The pathobiome represents a potential therapeutic target in