Unveiling the molecular complexity of intestinal ischemia–reperfusion injury through omics technologies

Abstract Intestinal ischemia–reperfusion injury (IR) is implicated in various clinical conditions and causes damage to the intestinal epithelium resulting in intestinal barrier loss. This presents a substantial clinical challenge, emphasizing the importance of gaining a comprehensive understanding of molecular events to aid in the identification of novel therapeutic targets. This review systematically explores the extent to which omics technologies—transcriptomics, proteomics, metabolomics, and metagenomics—have already contributed to deciphering the molecular mechanisms contributing to intestinal IR injury, in in vivo and in vitro animal and human models, and in clinical samples. Recent breakthroughs involve applying omics methodologies on exosomes, organoids, and single cells, shedding light on promising avenues and valuable targets to reduce intestinal IR injury. Future directions aimed at expediting clinical translation are discussed as well and include multi‐omics data integration to facilitate the identification of key regulatory nodes driving intestinal IR injury and advancing human organoid models based on the novel insights by single‐cell omics technologies, offering hope for clinical application of therapeutic strategies in the years to come.