Integrated multi-omics reveal important roles of gut contents in intestinal ischemia–reperfusion induced injuries in rats

Intestinal ischemia–reperfusion (IIR) is a life-threatening clinical event with damaging signals whose origin and contents are unclear. Here we observe that IIR significantly affect the metabolic profiles of most organs by unbiased organ-wide metabolic analysis of gut contents, blood, and fifteen organs in rats (n = 29). Remarkably, correlations between gut content metabolic profiles and those of other organs are the most significant. Gut contents are also the only ones to show dynamic correlations during IIR. Additionally, according to targeted metabolomics analysis, several neurotransmitters are considerably altered in the gut during IIR, and displayed noteworthy correlations with remote organs. Likewise, metagenomics analysis (n = 35) confirm the effects of IIR on gut microbiota, and identify key species fundamental to the changes in gut metabolites, particularly neurotransmitters. Our multi-omics results establish key roles of gut contents in IIR induced remote injury and provide clues for future exploration.