Intestinal ischemia/reperfusion (I/R) injury initiates a systemic inflammatory response syndrome with a high associated mortality rate. Early diagnosis is essential for reducing surgical mortality, yet current clinical biomarkers are insufficient. Metabonomics is a novel strategy for studying intestinal I/R, which may be used as part of a systems approach for quantitatively analyzing the intestinal microbiome during gut injury. By deconvolving the mammalian-microbial symbiotic relationship systems biology thus has the potential for personalized risk stratification in patients exposed to intestinal I/R. This review describes the mechanism of intestinal I/R and explores the essential role of the intestinal microbiota in the initiation of systemic inflammatory response syndrome. Furthermore, it analyzes current and future approaches for elucidating the mechanism of this condition.