Intestinal ischemia/reperfusion (I/R) injury is a serious condition related to blood flow disruption that commonly occurs in patients who are critically ill or undergoing certain surgeries. Some individuals are more susceptible to intestinal I/R injury than others, possibly due to gut microbiome differences. To find out more, researchers recently examined the microbiomes of mice subjected to cardiopulmonary bypass surgery. Some of the mice were sensitive to I/R injury (Sen mice), while others were resistant (Res mice). Sequencing revealed that the Sen and Res mice had different microbiota compositions before surgery. Interestingly, the species Lactobacillus murinus was much more abundant in Res mice than in Sen mice. Pretreating mice with L. murinus prevented intestinal I/R injury and improved survival via immune cells called macrophages. In vitro, L. murinus appeared to exert its beneficial effects by causing macrophages to release the protein IL-10 through the protein TLR2. Notably, an analysis of clinical data indicated that L. murinus abundance is also tightly linked to intestinal I/R injury severity in humans who undergo cardiopulmonary bypass. Although more research is needed, the results reveal a new microbe-related mechanism of intestinal I/R injury and suggest that L. murinus supplementation might help prevent this dangerous condition.