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Gastrointestinal Physiology and Diseases pp 77–87Cite as

NMR-Based Metabolomic Analysis of Normal and Inflamed Gut

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1422))

Abstract

Crohn’s disease and ulcerative colitis, the two major forms of idiopathic inflammatory bowel disease (IBD), are thought to occur through a loss of intestinal barrier leading to an inappropriate immune response toward intestinal microbiota. While genome-wide association studies (GWAS) have provided much information about susceptibility loci associated with these diseases, the etiology of IBD is still unknown. Metabolomic analysis allows for the comprehensive measurement of multiple small molecule metabolites in biological samples. During the past decade, metabolomic techniques have yielded novel and potentially important findings, revealing insight into metabolic perturbations associated with these diseases. This chapter provides metabolomic methodologies describing a nuclear magnetic resonance (NMR)-based non-targeted approach that has been utilized to make important contributions toward a better understanding of IBD.

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References

  1. Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640

    Article  CAS  PubMed  Google Scholar 

  2. Brand S (2009) Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease. Gut 58:1152–1167

    Article  CAS  PubMed  Google Scholar 

  3. Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434

    Article  CAS  PubMed  Google Scholar 

  4. Khor B, Gardet A, Xavier RJ (2011) Genetics and pathogenesis of inflammatory bowel disease. Nature 474:307–317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Manichanh C, Borruel N, Casellas F, Guarner F (2012) The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol 9:599–608

    Article  CAS  PubMed  Google Scholar 

  6. Sartor RB (1995) Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn’s disease. Gastroenterol Clin North Am 24:475–507

    CAS  PubMed  Google Scholar 

  7. Danese S, Dejana E, Fiocchi C (2007) Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J Immunol 178:6017–6022

    Article  CAS  PubMed  Google Scholar 

  8. Hatoum OA, Binion DG, Gutterman DD (2005) Paradox of simultaneous intestinal ischaemia and hyperaemia in inflammatory bowel disease. Eur J Clin Invest 35:599–609

    Article  CAS  PubMed  Google Scholar 

  9. Haddad JJ (2003) Science review: redox and oxygen-sensitive transcription factors in the regulation of oxidant-mediated lung injury: role for hypoxia-inducible factor-1alpha. Crit Care 7:47–54

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kokura S, Yoshida N, Yoshikawa T (2002) Anoxia/reoxygenation-induced leukocyte-endothelial cell interactions. Free Radic Biol Med 33:427–432

    Article  CAS  PubMed  Google Scholar 

  11. Saadi S, Wrenshall LE, Platt JL (2002) Regional manifestations and control of the immune system. FASEB J 16:849–856

    Article  CAS  PubMed  Google Scholar 

  12. Cummins EP, Seeballuck F, Keely SJ et al (2008) The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology 134:156–165

    Article  CAS  PubMed  Google Scholar 

  13. Semenza GL (2009) Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda) 24:97–106

    Article  CAS  Google Scholar 

  14. Furuta GT, Turner JR, Taylor CT et al (2001) Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J Exp Med 193:1027–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Glover LE, Colgan SP (2011) Hypoxia and metabolic factors that influence inflammatory bowel disease pathogenesis. Gastroenterology 140:1748–1755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jostins L, Ripke S, Weersma RK et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cho JH (2008) The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 8:458–466

    Article  CAS  PubMed  Google Scholar 

  18. Dettmer K, Aronov PA, Hammock BD (2007) Mass spectrometry-based metabolomics. Mass Spectrom Rev 26:51–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dunn WB, Bailey NJ, Johnson HE (2005) Measuring the metabolome: current analytical technologies. Analyst 130:606–625

    Article  CAS  PubMed  Google Scholar 

  20. Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E, Lindon JC, Nicholson JK (2007) Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc 2:2692–2703

    Article  CAS  PubMed  Google Scholar 

  21. Andriulli A, Loperfido S, Napolitano G et al (2007) Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol 102:1781–1788

    Article  PubMed  Google Scholar 

  22. Glunde K, Serkova NJ (2006) Therapeutic targets and biomarkers identified in cancer choline phospholipid metabolism. Pharmacogenomics 7:1109–1123

    Article  CAS  PubMed  Google Scholar 

  23. Klawitter J, Kominsky DJ, Brown JL et al (2009) Metabolic characteristics of imatinib resistance in chronic myeloid leukaemia cells. Br J Pharmacol 158:588–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kominsky DJ, Klawitter J, Brown JL, Boros LG, Melo JV, Eckhardt SG, Serkova NJ (2009) Abnormalities in glucose uptake and metabolism in imatinib-resistant human BCR-ABL-positive cells. Clin Cancer Res 15:3442–3450

    Article  CAS  PubMed  Google Scholar 

  25. Kominsky DJ, Keely S, MacManus CF et al (2011) An endogenously anti-inflammatory role for methylation in mucosal inflammation identified through metabolite profiling. J Immunol 186:6505–6514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Romick-Rosendale LE, Goodpaster AM, Hanwright PJ, Patel NB, Wheeler ET, Chona DL, Kennedy MA (2009) NMR-based metabonomics analysis of mouse urine and fecal extracts following oral treatment with the broad-spectrum antibiotic enrofloxacin (Baytril). Magn Reson Chem 47(Suppl 1):S36–S46

    Article  CAS  PubMed  Google Scholar 

  27. Schicho R, Nazyrova A, Shaykhutdinov R, Duggan G, Vogel HJ, Storr M (2010) Quantitative metabolomic profiling of serum and urine in DSS-induced ulcerative colitis of mice by (1)H NMR spectroscopy. J Proteome Res 9:6265–6273

    Article  CAS  PubMed  Google Scholar 

  28. Hong YS, Ahn YT, Park JC et al (2010) 1H NMR-based metabonomic assessment of probiotic effects in a colitis mouse model. Arch Pharm Res 33:1091–1101

    Article  CAS  PubMed  Google Scholar 

  29. Dong F, Zhang L, Hao F, Tang H, Wang Y (2013) Systemic responses of mice to dextran sulfate sodium-induced acute ulcerative colitis using 1H NMR spectroscopy. J Proteome Res 12:2958–2966

    Article  CAS  PubMed  Google Scholar 

  30. Williams HR, Cox IJ, Walker DG et al (2009) Characterization of inflammatory bowel disease with urinary metabolic profiling. Am J Gastroenterol 104:1435–1444

    Article  CAS  PubMed  Google Scholar 

  31. Williams HR, Willsmore JD, Cox IJ, Walker DG, Cobbold JF, Taylor-Robinson SD, Orchard TR (2012) Serum metabolic profiling in inflammatory bowel disease. Dig Dis Sci 57:2157–2165

    Article  CAS  PubMed  Google Scholar 

  32. Jacobs DM, Deltimple N, van Velzen E, van Dorsten FA, Bingham M, Vaughan EE, van Duynhoven J (2008) (1)H NMR metabolite profiling of feces as a tool to assess the impact of nutrition on the human microbiome. NMR Biomed 21:615–626

    Article  CAS  PubMed  Google Scholar 

  33. Marchesi JR, Holmes E, Khan F, Kochhar S, Scanlan P, Shanahan F, Wilson ID, Wang Y (2007) Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. J Proteome Res 6:546–551

    Article  CAS  PubMed  Google Scholar 

  34. Bjerrum JT, Wang Y, Hao F, Coskun M, Ludwig C, Gunther U, Nielsen OH (2015) Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn’s disease and healthy individuals. Metabolomics 11:122–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Balasubramanian K, Kumar S, Singh RR, Sharma U, Ahuja V, Makharia GK, Jagannathan NR (2009) Metabolism of the colonic mucosa in patients with inflammatory bowel diseases: an in vitro proton magnetic resonance spectroscopy study. Magn Reson Imaging 27:79–86

    Article  CAS  PubMed  Google Scholar 

  36. Bjerrum JT, Nielsen OH, Hao F, Tang H, Nicholson JK, Wang Y, Olsen J (2010) Metabonomics in ulcerative colitis: diagnostics, biomarker identification, and insight into the pathophysiology. J Proteome Res 9:954–962

    Article  CAS  PubMed  Google Scholar 

  37. Sharma U, Singh RR, Ahuja V, Makharia GK, Jagannathan NR (2010) Similarity in the metabolic profile in macroscopically involved and un-involved colonic mucosa in patients with inflammatory bowel disease: an in vitro proton ((1)H) MR spectroscopy study. Magn Reson Imaging 28:1022–1029

    Article  PubMed  Google Scholar 

  38. Serkova NJ, Glunde K (2009) Metabolomics of cancer. Methods Mol Biol 520:273–295

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, The University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Daniel J. Kao, Jordi M. Lanis & Erica Alexeev

  2. Mucosal Inflammation Program, The University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Daniel J. Kao, Jordi M. Lanis & Erica Alexeev

  3. Department of Microbiology and Immunology, Montana State University, 109 Lewis Hall, Bozeman, MT, 59717, USA

    Douglas J. Kominsky

Authors
  1. Daniel J. Kao
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  2. Jordi M. Lanis
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  3. Erica Alexeev
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  4. Douglas J. Kominsky
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Corresponding author

Correspondence to Douglas J. Kominsky .

Editor information

Editors and Affiliations

  1. Dept of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU, Richmond, Virginia, USA

    Andrei I. Ivanov

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Kao, D.J., Lanis, J.M., Alexeev, E., Kominsky, D.J. (2016). NMR-Based Metabolomic Analysis of Normal and Inflamed Gut. In: Ivanov, A. (eds) Gastrointestinal Physiology and Diseases. Methods in Molecular Biology, vol 1422. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3603-8_8

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  • DOI: https://doi.org/10.1007/978-1-4939-3603-8_8

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3601-4

  • Online ISBN: 978-1-4939-3603-8

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