{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:43:40Z","timestamp":1789015420700,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Intestinal ischemia\/reperfusion (I\/R) injury is a grave condition with high morbidity and mortality. We previously confirmed that intestinal I\/R induces intestinal flora disorders and changes in metabolites, but the role of different metabolites in intestinal I\/R injury is currently unclear. Based on targeted metabolic sequencing, pravastatin (PA) was determined to be a metabolite of the gut microbiota. Further, intestinal I\/R model mice were established through superior mesenteric artery obstruction. In addition, a co-culture model of small intestinal organoids and type II innate lymphoid cells (ILC2s) was subjected to hypoxia\/reoxygenation (H\/R) to simulate an intestinal I\/R model. Moreover, correlation analysis between the PA level in preoperative feces of patients undergoing cardiopulmonary bypass and the indices of postoperative intestinal I\/R injury was carried out. IL-33-deficient mice, ILC2-deleted mice, and anti-IL-13 neutralizing antibodies were also used to explore the potential mechanism through which PA attenuates intestinal I\/R injury. We demonstrated that PA levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with the indices of postoperative intestinal I\/R injury. Furthermore, PA alleviated intestinal I\/R injury and improved the survival of mice. We further showed that PA promotes IL-13 release from ILC2s by activating IL-33\/ST2 signaling to attenuate intestinal I\/R injury. In addition, IL-13 promoted the self-renewal of intestinal stem cells by activating Notch1 and Wnt signals. Overall, results indicated that the gut microbial metabolite PA can attenuate intestinal I\/R injury by promoting the release of IL-13 from ILC2s <jats:italic>via<\/jats:italic> IL-33\/ST2 signaling, revealing a novel mechanism of and therapeutic strategy for intestinal I\/R injury.<\/jats:p>","DOI":"10.3389\/fimmu.2021.704836","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T06:19:06Z","timestamp":1632809946000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":42,"title":["Gut Microbial Metabolite Pravastatin Attenuates Intestinal Ischemia\/Reperfusion Injury Through Promoting IL-13 Release From Type II Innate Lymphoid Cells via IL\u221233\/ST2 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