{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T23:30:52Z","timestamp":1778801452235,"version":"3.51.4"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intestinal ischemia\u2013reperfusion (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 (<jats:italic>n<\/jats:italic>\u2009=\u200929). 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 (<jats:italic>n<\/jats:italic>\u2009=\u200935) 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.<\/jats:p>","DOI":"10.1038\/s42003-022-03887-8","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T16:20:28Z","timestamp":1662740428000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Integrated multi-omics reveal important roles of gut contents in intestinal ischemia\u2013reperfusion induced injuries in rats"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-8046","authenticated-orcid":false,"given":"Die","family":"Dai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fandie","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingchao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menglu","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyue","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-9276","authenticated-orcid":false,"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zunjian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengguo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-6147","authenticated-orcid":false,"given":"Wei-Hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"3887_CR1","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1023\/B:DDAS.0000042232.98927.91","volume":"49","author":"IH Mallick","year":"2004","unstructured":"Mallick, I. H., Yang, W., Winslet, M. C. & Seifalian, A. M. Ischemia\u2013reperfusion injury of the intestine and protective strategies against injury. Dig. Dis. Sci. 49, 1359\u20131377 (2004).","journal-title":"Dig. Dis. Sci."},{"key":"3887_CR2","doi-asserted-by":"publisher","first-page":"G299","DOI":"10.1152\/ajpgi.1989.257.2.G299","volume":"257","author":"MJ Mangino","year":"1989","unstructured":"Mangino, M. J., Anderson, C. B., Murphy, M. K., Brunt, E. & Turk, J. Mucosal arachidonate metabolism and intestinal ischemia-reperfusion injury. Am. J. Physiol. Gastrointest. Liver Physiol. 257, G299\u2013G307 (1989).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"3887_CR3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00423-010-0727-x","volume":"396","author":"B Vollmar","year":"2010","unstructured":"Vollmar, B. & Menger, M. D. Intestinal ischemia\/reperfusion: microcirculatory pathology and functional consequences. Langenbecks Arch. Surg. 396, 13\u201329 (2010).","journal-title":"Langenbecks Arch. Surg."},{"key":"3887_CR4","doi-asserted-by":"crossref","unstructured":"Pan, T., Yang, J. & Jiang, H. In Proceedings of the 2020 2nd International Conference on Intelligent Medicine and Image Processing 19\u201323 (Association for Computing Machinery, 2020).","DOI":"10.1145\/3399637.3399647"},{"key":"3887_CR5","doi-asserted-by":"publisher","first-page":"104444","DOI":"10.1016\/j.yexmp.2020.104444","volume":"115","author":"X-M Liu","year":"2020","unstructured":"Liu, X.-M. et al. Dexmedetomidine protects intestinal ischemia-reperfusion injury via inhibiting p38 MAPK cascades. Exp. Mol. Pathol. 115, 104444 (2020).","journal-title":"Exp. Mol. Pathol."},{"key":"3887_CR6","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1038\/s41418-019-0299-4","volume":"26","author":"Y Li","year":"2019","unstructured":"Li, Y. et al. Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia\/reperfusion. Cell Death Differ. 26, 2284\u20132299 (2019).","journal-title":"Cell Death Differ."},{"key":"3887_CR7","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.3892\/mmr.2020.11270","volume":"22","author":"Z Zeng","year":"2020","unstructured":"Zeng, Z. et al. Aggravated intestinal ischemia\u2011reperfusion injury is associated with activated mitochondrial autophagy in a mouse model of diabetes. Mol. Med. Rep. 22, 1892\u20131900 (2020).","journal-title":"Mol. Med. Rep."},{"key":"3887_CR8","doi-asserted-by":"publisher","first-page":"e25","DOI":"10.1016\/j.jpeds.2010.11.009","volume":"158","author":"CM Young","year":"2011","unstructured":"Young, C. M., Kingma, S. D. K. & Neu, J. Ischemia-reperfusion and neonatal intestinal injury. J. Pediatr. 158, e25\u2013e28 (2011).","journal-title":"J. Pediatr."},{"key":"3887_CR9","doi-asserted-by":"publisher","first-page":"4384","DOI":"10.1096\/fj.201900817R","volume":"34","author":"S Wen","year":"2020","unstructured":"Wen, S. et al. HMGB1-associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia\/reperfusion in rats. FASEB J. 34, 4384\u20134402 (2020).","journal-title":"FASEB J."},{"key":"3887_CR10","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s10620-016-4328-6","volume":"62","author":"Y Jin","year":"2017","unstructured":"Jin, Y. & Blikslager, A. T. Intestinal ischemia\u2013reperfusion: rooting for the SOCS. Dig. Dis. Sci. 62, 4\u20136 (2017).","journal-title":"Dig. Dis. Sci."},{"key":"3887_CR11","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1097\/00000542-200106000-00030","volume":"94","author":"CD Collard","year":"2001","unstructured":"Collard, C. D. & Gelman, S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology 94, 1133\u20131138 (2001).","journal-title":"Anesthesiology"},{"key":"3887_CR12","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.kjms.2018.05.006","volume":"34","author":"L Zhang","year":"2018","unstructured":"Zhang, L., Zhang, F., He, D.-K., Fan, X.-M. & Shen, J. MicroRNA-21 is upregulated during intestinal barrier dysfunction induced by ischemia reperfusion. Kaohsiung J. Med. Sci. 34, 556\u2013563 (2018).","journal-title":"Kaohsiung J. Med. Sci."},{"key":"3887_CR13","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/S1590-8658(02)80089-5","volume":"34","author":"Z Sun","year":"2002","unstructured":"Sun, Z., Lasson, \u00c5., Olanders, K., Deng, X. & Andersson, R. Gut barrier permeability, reticuloendothelial system function and protease inhibitor levels following intestinal ischaemia and reperfusion - effects of pretreatment with N-acetyl-L-cysteine and indomethacin. Digestive Liver Dis. 34, 560\u2013569 (2002).","journal-title":"Digestive Liver Dis."},{"key":"3887_CR14","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/BF01852385","volume":"184","author":"M Younes","year":"1984","unstructured":"Younes, M. et al. Oxidative tissue damage following regional intestinal ischemia and reperfusion in the cat. Res. Exp. Med. 184, 259\u2013264 (1984).","journal-title":"Res. Exp. Med."},{"key":"3887_CR15","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.lfs.2017.08.032","volume":"189","author":"I Turan","year":"2017","unstructured":"Turan, I., Ozacmak, H. S., Ozacmak, V. H., Barut, F. & Arasl\u0131, M. Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats. Life Sci. 189, 23\u201328 (2017).","journal-title":"Life Sci."},{"key":"3887_CR16","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.redox.2015.08.020","volume":"6","author":"DN Granger","year":"2015","unstructured":"Granger, D. N. & Kvietys, P. R. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol. 6, 524\u2013551 (2015).","journal-title":"Redox Biol."},{"key":"3887_CR17","doi-asserted-by":"publisher","first-page":"G1020","DOI":"10.1152\/ajpgi.00239.2011","volume":"301","author":"K Yoshiya","year":"2011","unstructured":"Yoshiya, K. et al. Depletion of gut commensal bacteria attenuates intestinal ischemia\/reperfusion injury. Am. J. Physiol. Gastrointest. Liver Physiol. 301, G1020\u2013G1030 (2011).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"3887_CR18","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s00383-019-04555-5","volume":"36","author":"H-y Zhang","year":"2020","unstructured":"Zhang, H.-y et al. Dual roles of commensal bacteria after intestinal ischemia and reperfusion. Pediatr. Surg. Int. 36, 81\u201391 (2020).","journal-title":"Pediatr. Surg. Int."},{"key":"3887_CR19","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3164\/jcbn.17-137","volume":"63","author":"Y Nadatani","year":"2018","unstructured":"Nadatani, Y. et al. Microbiome and intestinal ischemia\/reperfusion injury. J. Clin. Biochem. Nutr. 63, 26\u201332 (2018).","journal-title":"J. Clin. Biochem. Nutr."},{"key":"3887_CR20","doi-asserted-by":"publisher","first-page":"e102217","DOI":"10.1371\/journal.pone.0102217","volume":"9","author":"C Joly Condette","year":"2014","unstructured":"Joly Condette, C. et al. Increased gut permeability and bacterial translocation after chronic chlorpyrifos exposure in rats. PLoS ONE 9, e102217 (2014).","journal-title":"PLoS ONE"},{"key":"3887_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ki.1996.1","volume":"49","author":"ML Halperin","year":"1996","unstructured":"Halperin, M. L. & Kamel, K. S. D-lactic acidosis: turning sugar into acids in the gastrointestinal tract. Kidney Int. 49, 1\u20138 (1996).","journal-title":"Kidney Int."},{"key":"3887_CR22","doi-asserted-by":"crossref","unstructured":"Kanda, T. et al. Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans. Gastroenterology 110, 339\u2013343 (1996).","DOI":"10.1053\/gast.1996.v110.pm8566578"},{"key":"3887_CR23","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.clnu.2008.02.005","volume":"27","author":"P Crenn","year":"2008","unstructured":"Crenn, P., Messing, B. & Cynober, L. Citrulline as a biomarker of intestinal failure due to enterocyte mass reduction. Clin. Nutr. 27, 328\u2013339 (2008).","journal-title":"Clin. Nutr."},{"key":"3887_CR24","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/0016-5085(88)90261-2","volume":"94","author":"SJH Van Deventer","year":"1988","unstructured":"Van Deventer, S. J. H., Ten Cate, J. W. & Tytgat, G. N. J. Intestinal endotoxemia: clinical significance. Gastroenterology 94, 825\u2013831 (1988).","journal-title":"Gastroenterology"},{"key":"3887_CR25","doi-asserted-by":"publisher","first-page":"6729","DOI":"10.1021\/ac051080y","volume":"77","author":"AK Smilde","year":"2005","unstructured":"Smilde, A. K., van der Werf, M. J., Bijlsma, S., van der Werff-van der Vat, B. J. & Jellema, R. H. Fusion of mass spectrometry-based metabolomics data. Anal. Chem. 77, 6729\u20136736 (2005).","journal-title":"Anal. Chem."},{"key":"3887_CR26","doi-asserted-by":"publisher","first-page":"e1005752","DOI":"10.1371\/journal.pcbi.1005752","volume":"13","author":"F Rohart","year":"2017","unstructured":"Rohart, F., Gautier, B., Singh, A. & L\u00ea Cao, K.-A. mixOmics: an R package for \u2018omics feature selection and multiple data integration. PLoS Comp. Biol. 13, e1005752 (2017).","journal-title":"PLoS Comp. Biol."},{"key":"3887_CR27","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1093\/bioinformatics\/bty1054","volume":"35","author":"A Singh","year":"2019","unstructured":"Singh, A. et al. DIABLO: an integrative approach for identifying key molecular drivers from multi-omics assays. Bioinformatics 35, 3055\u20133062 (2019).","journal-title":"Bioinformatics"},{"key":"3887_CR28","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.ab.2012.10.011","volume":"433","author":"B Worley","year":"2013","unstructured":"Worley, B., Halouska, S. & Powers, R. Utilities for quantifying separation in PCA\/PLS-DA scores plots. Anal. Biochem. 433, 102\u2013104 (2013).","journal-title":"Anal. Biochem."},{"key":"3887_CR29","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1016\/j.cell.2018.08.042","volume":"174","author":"KA Dyar","year":"2018","unstructured":"Dyar, K. A. et al. Atlas of circadian metabolism reveals system-wide coordination and communication between clocks. Cell 174, 1571\u20131585.e1511 (2018).","journal-title":"Cell"},{"key":"3887_CR30","doi-asserted-by":"publisher","unstructured":"Dalangin, R., Kim, A. & Campbell, R. E. The role of amino acids in neurotransmission and fluorescent tools for their detection. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms21176197 (2020).","DOI":"10.3390\/ijms21176197"},{"key":"3887_CR31","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/jnc.14709","volume":"149","author":"K Gao","year":"2019","unstructured":"Gao, K. et al. Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: aromatic amino acids linking the microbiota\u2013brain axis. J. Neurochem. 149, 641\u2013659 (2019).","journal-title":"J. Neurochem."},{"key":"3887_CR32","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/0165-0173(95)00016-X","volume":"21","author":"A Blokland","year":"1995","unstructured":"Blokland, A. Acetylcholine: a neurotransmitter for learning and memory? Brain Res. Rev. 21, 285\u2013300 (1995).","journal-title":"Brain Res. Rev."},{"key":"3887_CR33","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/S0014-5793(00)02401-7","volume":"488","author":"F Papes","year":"2001","unstructured":"Papes, F., Surpili, M. J., Langone, F., Trigo, J. R. & Arruda, P. The essential amino acid lysine acts as precursor of glutamate in the mammalian central nervous system. FEBS Lett. 488, 34\u201338 (2001).","journal-title":"FEBS Lett."},{"key":"3887_CR34","doi-asserted-by":"publisher","unstructured":"El-Yassimi, A., Hichami, A., Besnard, P. & Khan, N. A. Linoleic acid induces calcium signaling, Src kinase phosphorylation, and neurotransmitter release in mouse CD36-positive gustatory cells. J. Biol. Chem. 283, 12949\u201312959 https:\/\/doi.org\/10.1074\/jbc.M707478200 (2008).","DOI":"10.1074\/jbc.M707478200"},{"key":"3887_CR35","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/0005-2744(69)90246-0","volume":"191","author":"KK Schlender","year":"1969","unstructured":"Schlender, K. K., Wei, S. H. & Villar-Palasi, C. UDP-glucose: glycogen \u03b1-4-glucosyltransferase I kinase activity of purified muscle protein kinase: cyclic nucleotide specificity. Biochim. Biophys. Acta. 191, 272\u2013278 (1969).","journal-title":"Biochim. Biophys. Acta."},{"key":"3887_CR36","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1007\/s00277-004-0983-3","volume":"84","author":"JB Schnog","year":"2005","unstructured":"Schnog, J. B. et al. Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell disease. Ann. Hematol. 84, 282\u2013286 (2005).","journal-title":"Ann. Hematol."},{"key":"3887_CR37","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1021\/jm00109a032","volume":"34","author":"GC Wallace","year":"1991","unstructured":"Wallace, G. C. & Fukuto, J. M. Synthesis and bioactivity of N.omega.-hydroxyarginine: a possible intermediate in the biosynthesis of nitric oxide from arginine. J. Med. Chem. 34, 1746\u20131748 (1991).","journal-title":"J. Med. Chem."},{"key":"3887_CR38","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/nrn2214","volume":"8","author":"V Calabrese","year":"2007","unstructured":"Calabrese, V. et al. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat. Rev. Neurosci. 8, 766\u2013775 (2007).","journal-title":"Nat. Rev. Neurosci."},{"key":"3887_CR39","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1152\/jn.1989.62.5.1018","volume":"62","author":"DA McCormick","year":"1989","unstructured":"McCormick, D. A. GABA as an inhibitory neurotransmitter in human cerebral cortex. J. Neurophysiol. 62, 1018\u20131027 (1989).","journal-title":"J. Neurophysiol."},{"key":"3887_CR40","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.cellsig.2008.07.011","volume":"21","author":"T Okada","year":"2009","unstructured":"Okada, T., Kajimoto, T., Jahangeer, S. & Nakamura, S.-I. Sphingosine kinase\/sphingosine 1-phosphate signalling in central nervous system. Cell. Signal. 21, 7\u201313 (2009).","journal-title":"Cell. Signal."},{"key":"3887_CR41","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1139\/o00-015","volume":"78","author":"KM Dhandapani","year":"2000","unstructured":"Dhandapani, K. M. & Brann, D. W. The role of glutamate and nitric oxide in the reproductive neuroendocrine system. Biochem. Cell Biol. 78, 165\u2013179 (2000).","journal-title":"Biochem. Cell Biol."},{"key":"3887_CR42","doi-asserted-by":"crossref","unstructured":"Auber, F. et al. Enteric nervous system impairment in gastroschisis. Eur. J. Pediatr. Surg. 23, 29\u201338 (2012).","DOI":"10.1055\/s-0032-1326955"},{"key":"3887_CR43","first-page":"1670","volume":"56","author":"B Geramizadeh","year":"2009","unstructured":"Geramizadeh, B., Hayati, K., Rahsaz, M. & Hosseini, S.-V. Assessing the interstitial cells of Cajal, cells of enteric nervous system and neurotransmitters in slow transit constipation, using immunohistochemistry for CD117, PGP9.5 and serotonin. Hepatogastroenterology 56, 1670\u20131674 (2009).","journal-title":"Hepatogastroenterology"},{"key":"3887_CR44","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1002\/biof.1097","volume":"39","author":"S Gonkowski","year":"2013","unstructured":"Gonkowski, S. Substance P as a neuronal factor in the enteric nervous system of the porcine descending colon in physiological conditions and during selected pathogenic processes. BioFactors 39, 542\u2013551 (2013).","journal-title":"BioFactors"},{"key":"3887_CR45","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1055\/s-2005-872949","volume":"15","author":"E Dzienis-Koronkiewicz","year":"2005","unstructured":"Dzienis-Koronkiewicz, E., Debek, W. & Chyczewski, L. Use of synaptophysin immunohistochemistry in intestinal motility disorders. Eur. J. Pediatr. Surg. 15, 392\u2013398 (2005).","journal-title":"Eur. J. Pediatr. Surg."},{"key":"3887_CR46","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/nmeth.3589","volume":"12","author":"DT Truong","year":"2015","unstructured":"Truong, D. T. et al. MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat. Methods 12, 902\u2013903 (2015).","journal-title":"Nat. Methods"},{"key":"3887_CR47","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/s41592-018-0176-y","volume":"15","author":"EA Franzosa","year":"2018","unstructured":"Franzosa, E. A. et al. Species-level functional profiling of metagenomes and metatranscriptomes. Nat. Methods 15, 962\u2013968 (2018).","journal-title":"Nat. Methods"},{"key":"3887_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-6749-z","volume":"21","author":"P Jiang","year":"2020","unstructured":"Jiang, P., Lai, S., Wu, S., Zhao, X.-M. & Chen, W.-H. Host DNA contents in fecal metagenomics as a biomarker for intestinal diseases and effective treatment. BMC Genomics 21, 348 (2020).","journal-title":"BMC Genomics"},{"key":"3887_CR49","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1038\/s41596-018-0064-z","volume":"13","author":"HK Pedersen","year":"2018","unstructured":"Pedersen, H. K. et al. A computational framework to integrate high-throughput \u2018-omics\u2019 datasets for the identification of potential mechanistic links. Nat. Protoc. 13, 2781\u20132800 (2018).","journal-title":"Nat. Protoc."},{"key":"3887_CR50","doi-asserted-by":"publisher","first-page":"346","DOI":"10.3390\/jcm7100346","volume":"7","author":"S-C Wu","year":"2018","unstructured":"Wu, S.-C. et al. Metagenome analysis as a tool to study bacterial infection associated with acute surgical abdomen. J. Clin. Med. 7, 346 (2018).","journal-title":"J. Clin. Med."},{"key":"3887_CR51","doi-asserted-by":"publisher","first-page":"17187","DOI":"10.1073\/pnas.0904847106","volume":"106","author":"AL Hartman","year":"2009","unstructured":"Hartman, A. L. et al. Human gut microbiome adopts an alternative state following small bowel transplantation. Proc. Natl Acad. Sci. USA 106, 17187 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3887_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-016-0216-8","volume":"4","author":"CJ Stewart","year":"2016","unstructured":"Stewart, C. J. et al. Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease. Microbiome 4, 67 (2016).","journal-title":"Microbiome"},{"key":"3887_CR53","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1016\/j.celrep.2016.03.015","volume":"14","author":"DoyleV Ward","year":"2016","unstructured":"Ward, DoyleV. et al. Metagenomic sequencing with strain-level resolution implicates uropathogenic E. coli in necrotizing enterocolitis and mortality in preterm infants. Cell Rep. 14, 2912\u20132924 (2016).","journal-title":"Cell Rep."},{"key":"3887_CR54","doi-asserted-by":"publisher","DOI":"10.1186\/2049-2618-1-20","volume":"1","author":"EC Claud","year":"2013","unstructured":"Claud, E. C. et al. Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants. Microbiome 1, 20 (2013).","journal-title":"Microbiome"},{"key":"3887_CR55","doi-asserted-by":"crossref","unstructured":"Freestone, P. P. et al. Growth stimulation of intestinal commensal Escherichia coli by catecholamines: a possible contributory factor in trauma-induced sepsis. Shock 18, 465\u2013470 (2002).","DOI":"10.1097\/00024382-200211000-00014"},{"key":"3887_CR56","doi-asserted-by":"publisher","first-page":"e00013","DOI":"10.1128\/mSystems.00013-15","volume":"1","author":"C Noecker","year":"2016","unstructured":"Noecker, C. et al. Metabolic model-based integration of microbiome taxonomic and metabolomic profiles elucidates mechanistic links between ecological and metabolic variation. mSystems 1, e00013\u2013e00015 (2016).","journal-title":"mSystems"},{"key":"3887_CR57","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s00441-010-1126-x","volume":"344","author":"LR Rivera","year":"2011","unstructured":"Rivera, L. R., Thacker, M., Pontell, L., Cho, H. J. & Furness, J. B. Deleterious effects of intestinal ischemia\/reperfusion injury in the mouse enteric nervous system are associated with protein nitrosylation. Cell Tissue Res. 344, 111\u2013123 (2011).","journal-title":"Cell Tissue Res."},{"key":"3887_CR58","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.conb.2019.12.003","volume":"62","author":"MF Linoy","year":"2020","unstructured":"Linoy, M. F., Evan, E. & Omry, K. The microbiota and the hypothalamus-pituitary-adrenocortical (HPA) axis, implications for anxiety and stress disorders. Curr. Opin. Neurobiol. 62, 76\u201382 (2020).","journal-title":"Curr. Opin. Neurobiol."},{"key":"3887_CR59","doi-asserted-by":"publisher","first-page":"572","DOI":"10.3389\/fncel.2019.00572","volume":"13","author":"J-J Yin","year":"2020","unstructured":"Yin, J.-J. et al. Dynamic balance of microglia and astrocytes involved in the remyelinating effect of ginkgolide B. Front. Cell. Neurosci. 13, 572 (2020).","journal-title":"Front. Cell. Neurosci."},{"key":"3887_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/srep34136","volume":"6","author":"D Dai","year":"2016","unstructured":"Dai, D. et al. Time-resolved metabolomics analysis of individual differences during the early stage of lipopolysaccharide-treated rats. Sci. Rep. 6, 34136 (2016).","journal-title":"Sci. Rep."},{"key":"3887_CR61","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-015-0892-6","volume":"12","author":"D Dai","year":"2015","unstructured":"Dai, D. et al. A pharmacometabonomic approach using predose serum metabolite profiles reveals differences in lipid metabolism in survival and non-survival rats treated with lipopolysaccharide. Metabolomics 12, 2 (2015).","journal-title":"Metabolomics"},{"key":"3887_CR62","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ab.2009.12.022","volume":"399","author":"MT Werth","year":"2010","unstructured":"Werth, M. T., Halouska, S., Shortridge, M. D., Zhang, B. & Powers, R. Analysis of metabolomic PCA data using tree diagrams. Anal. Biochem. 399, 58\u201363 (2010).","journal-title":"Anal. Biochem."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03887-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03887-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03887-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T15:29:22Z","timestamp":1727969362000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03887-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3887"],"URL":"https:\/\/doi.org\/10.1038\/s42003-022-03887-8","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]},"assertion":[{"value":"25 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"938"}}