Skip to main content
Erschienen in: Inflammation Research 1/2017

21.10.2016 | Original Research Paper

1H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation

verfasst von: Raj Kumar Sharma, Kumudesh Mishra, Alvina Farooqui, Anu Behari, Vinay Kumar Kapoor, Neeraj Sinha

Erschienen in: Inflammation Research | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Objective and design

We present in this article 1H nuclear magnetic resonance (NMR)-based metabolic approach to screen the serum metabolic alterations in human gallbladder inflammation with chronic cholecystitis (CC).

Material/methods

Total of 71 human serum samples was divided into two groups, (n = 41, CC) and (n = 30 control). 1H NMR metabolic profiling was carried out for investigation of metabolic alterations. Multivariate statistical analysis was applied for pattern recognition and identification of metabolites playing crucial role in gallbladder inflammation. Receiver operating curve (ROC) and pathway analysis on NMR data were also carried out to validate the findings.

Results

Serum metabolites such as glutamine, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), alanine, branch chained amino acids (BCAA), histidine and tyrosine were found to be depleted whereas formate, lactate, 1,2-propanediol were found to be elevated in CC. Metabolic pathways associated with metabolite alteration have also been reported.

Conclusions

NMR has been established for disease diagnosis along with identification of metabolic pattern recognition in biofluids. Gallstones cause inflammation of the gallbladder in the form of CC. Inflammation plays a major role in causation of gall bladder cancer and leads the way to malignancy. Metabolic analysis of CC may lead to early diagnosis of disease and its progression to gallbladder cancer.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer. 2004;4:695–706.CrossRefPubMed Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer. 2004;4:695–706.CrossRefPubMed
2.
3.
Zurück zum Zitat Priya TP, Kapoor VK, Krishnani N, Agrawal V, Agrawal S. Role of E-cadherin gene in gall bladder cancer and its precursor lesions. Virchows Arch. 2010;456:507–14.CrossRefPubMed Priya TP, Kapoor VK, Krishnani N, Agrawal V, Agrawal S. Role of E-cadherin gene in gall bladder cancer and its precursor lesions. Virchows Arch. 2010;456:507–14.CrossRefPubMed
4.
Zurück zum Zitat Maurer KJ, Carey MC, Fox JG. Roles of infection, inflammation, and the immune system in cholesterol gallstone formation. Gastroenterology. 2009;136:425–40.CrossRefPubMed Maurer KJ, Carey MC, Fox JG. Roles of infection, inflammation, and the immune system in cholesterol gallstone formation. Gastroenterology. 2009;136:425–40.CrossRefPubMed
5.
Zurück zum Zitat Singh VP, Rajesh S, Bihari C, Desai SN, Pargewar SS, Arora A. Xanthogranulomatous cholecystitis: what every radiologist should know. World J Radiol. 2016;8:183–91.CrossRefPubMedPubMedCentral Singh VP, Rajesh S, Bihari C, Desai SN, Pargewar SS, Arora A. Xanthogranulomatous cholecystitis: what every radiologist should know. World J Radiol. 2016;8:183–91.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Schottenfeld D, Beebe-Dimmer J. Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin. 2006;56:69–83.CrossRefPubMed Schottenfeld D, Beebe-Dimmer J. Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin. 2006;56:69–83.CrossRefPubMed
7.
Zurück zum Zitat van Erpecum KJ. Biliary lipids, water and cholesterol gallstones. Biol Cell. 2005;97:815–22.CrossRefPubMed van Erpecum KJ. Biliary lipids, water and cholesterol gallstones. Biol Cell. 2005;97:815–22.CrossRefPubMed
8.
Zurück zum Zitat Carey MC. Biliary lipids and gallstone formation. In: Csomós G, Thaler H, editors. Clinical hepatology: history present state outlook. Berlin: Springer; 1983. p. 52–69.CrossRef Carey MC. Biliary lipids and gallstone formation. In: Csomós G, Thaler H, editors. Clinical hepatology: history present state outlook. Berlin: Springer; 1983. p. 52–69.CrossRef
9.
Zurück zum Zitat Behar J. Physiology and pathophysiology of the biliary tract: the gallbladder and sphincter of Oddi—A review. ISRN Physiol. 2013;2013:15.CrossRef Behar J. Physiology and pathophysiology of the biliary tract: the gallbladder and sphincter of Oddi—A review. ISRN Physiol. 2013;2013:15.CrossRef
10.
Zurück zum Zitat Raffler J, Friedrich N, Arnold M, Kacprowski T, Rueedi R, Altmaier E, et al. Genome-wide association study with targeted and non-targeted nmr metabolomics identifies 15 novel loci of urinary human metabolic individuality. PLoS Genet. 2015;11:e1005487.CrossRefPubMedPubMedCentral Raffler J, Friedrich N, Arnold M, Kacprowski T, Rueedi R, Altmaier E, et al. Genome-wide association study with targeted and non-targeted nmr metabolomics identifies 15 novel loci of urinary human metabolic individuality. PLoS Genet. 2015;11:e1005487.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Zhang A, Sun H, Wang P, Han Y, Wang X. Recent and potential developments of biofluid analyses in metabolomics. J Proteom. 2012;75:1079–88.CrossRef Zhang A, Sun H, Wang P, Han Y, Wang X. Recent and potential developments of biofluid analyses in metabolomics. J Proteom. 2012;75:1079–88.CrossRef
12.
Zurück zum Zitat Chen Z, Kim J. Urinary proteomics and metabolomics studies to monitor bladder health and urological diseases. BMC Urol. 2016;16:016–0129.CrossRef Chen Z, Kim J. Urinary proteomics and metabolomics studies to monitor bladder health and urological diseases. BMC Urol. 2016;16:016–0129.CrossRef
13.
Zurück zum Zitat Kork F, Gentsch A, Holthues J, Hellweg R, Jankowski V, Tepel M, et al. A biomarker for severity of Alzheimer’s disease: 1H-NMR resonances in cerebrospinal fluid correlate with performance in mini-mental-state-exam. Biomarkers. 2012;17:36–42.CrossRefPubMed Kork F, Gentsch A, Holthues J, Hellweg R, Jankowski V, Tepel M, et al. A biomarker for severity of Alzheimer’s disease: 1H-NMR resonances in cerebrospinal fluid correlate with performance in mini-mental-state-exam. Biomarkers. 2012;17:36–42.CrossRefPubMed
14.
Zurück zum Zitat Singh C, Rai R, Azim A, Sinha N, Ahmed A, Singh K, et al. Metabolic profiling of human lung injury by 1H high-resolution nuclear magnetic resonance spectroscopy of blood serum. Metabolomics. 2015;11:166–74.CrossRef Singh C, Rai R, Azim A, Sinha N, Ahmed A, Singh K, et al. Metabolic profiling of human lung injury by 1H high-resolution nuclear magnetic resonance spectroscopy of blood serum. Metabolomics. 2015;11:166–74.CrossRef
15.
Zurück zum Zitat Gupta A, Dwivedi M, Mahdi AA, Khetrapal CL, Bhandari M. Broad identification of bacterial type in urinary tract infection using 1H NMR spectroscopy. J Proteome Res. 2012;11:1844–54.CrossRefPubMed Gupta A, Dwivedi M, Mahdi AA, Khetrapal CL, Bhandari M. Broad identification of bacterial type in urinary tract infection using 1H NMR spectroscopy. J Proteome Res. 2012;11:1844–54.CrossRefPubMed
16.
Zurück zum Zitat Nagana Gowda GA, Somashekar BS, Ijare OB, Sharma A, Kapoor VK, Khetrapal CL. One-step analysis of major bile components in human bile using 1H NMR spectroscopy. Lipids. 2006;41(6):577–89. Nagana Gowda GA, Somashekar BS, Ijare OB, Sharma A, Kapoor VK, Khetrapal CL. One-step analysis of major bile components in human bile using 1H NMR spectroscopy. Lipids. 2006;41(6):577–89.
17.
Zurück zum Zitat Viswan A, Sharma RK, Azim A, Sinha N. NMR-based metabolic snapshot from minibronchoalveolar lavage fluid: an approach to unfold human respiratory metabolomics. J Proteome Res. 2016;15(1):302–10. Viswan A, Sharma RK, Azim A, Sinha N. NMR-based metabolic snapshot from minibronchoalveolar lavage fluid: an approach to unfold human respiratory metabolomics. J Proteome Res. 2016;15(1):302–10.
18.
Zurück zum Zitat Jayalakshmi K, Sonkar K, Behari A, Kapoor VK, Sinha N. Lipid profiling of cancerous and benign gallbladder tissues by 1H NMR spectroscopy. NMR Biomed. 2011;24:335–42.PubMed Jayalakshmi K, Sonkar K, Behari A, Kapoor VK, Sinha N. Lipid profiling of cancerous and benign gallbladder tissues by 1H NMR spectroscopy. NMR Biomed. 2011;24:335–42.PubMed
19.
Zurück zum Zitat Nagana Gowda GA, Raftery D. NMR spectroscopy-based metabolic profiling for detecting hepatobiliary diseases. Emerging trends in dietary components for preventing and combating disease. Am Chem Soc. 2012;1093:407–15. Nagana Gowda GA, Raftery D. NMR spectroscopy-based metabolic profiling for detecting hepatobiliary diseases. Emerging trends in dietary components for preventing and combating disease. Am Chem Soc. 2012;1093:407–15.
20.
Zurück zum Zitat Holmes E, Wijeyesekera A, Taylor-Robinson SD, Nicholson JK. The promise of metabolic phenotyping in gastroenterology and hepatology. Nat Rev Gastroenterol Hepatol. 2015;12:458–71.CrossRefPubMed Holmes E, Wijeyesekera A, Taylor-Robinson SD, Nicholson JK. The promise of metabolic phenotyping in gastroenterology and hepatology. Nat Rev Gastroenterol Hepatol. 2015;12:458–71.CrossRefPubMed
21.
Zurück zum Zitat Kimhofer T, Fye H, Taylor-Robinson S, Thursz M, Holmes E. Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review. Br J Cancer. 2015;112:1141–56.CrossRefPubMedPubMedCentral Kimhofer T, Fye H, Taylor-Robinson S, Thursz M, Holmes E. Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review. Br J Cancer. 2015;112:1141–56.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Murakami Y, Kubo S, Tamori A, Itami S, Kawamura E, Iwaisako K, et al. Comprehensive analysis of transcriptome and metabolome analysis in Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma. Sci Rep. 2015;5:16294.CrossRefPubMedPubMedCentral Murakami Y, Kubo S, Tamori A, Itami S, Kawamura E, Iwaisako K, et al. Comprehensive analysis of transcriptome and metabolome analysis in Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma. Sci Rep. 2015;5:16294.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Kapoor VK. Gall bladder cancer: what needs to be done in India? In: Gandhi V, Mehta K, Grover R, Pathak S, Aggarwal BB, editors. Multi-targeted approach to treatment of cancer. Berlin: Springer International Publishing; 2015. p. 179–87. Kapoor VK. Gall bladder cancer: what needs to be done in India? In: Gandhi V, Mehta K, Grover R, Pathak S, Aggarwal BB, editors. Multi-targeted approach to treatment of cancer. Berlin: Springer International Publishing; 2015. p. 179–87.
24.
Zurück zum Zitat Schicho R, Shaykhutdinov R, Ngo J, Nazyrova A, Schneider C, Panaccione R, et al. Quantitative metabolomic profiling of serum, plasma, and urine by (1)H NMR spectroscopy discriminates between patients with inflammatory bowel disease and healthy individuals. J Proteome Res. 2012;11:3344–57.CrossRefPubMedPubMedCentral Schicho R, Shaykhutdinov R, Ngo J, Nazyrova A, Schneider C, Panaccione R, et al. Quantitative metabolomic profiling of serum, plasma, and urine by (1)H NMR spectroscopy discriminates between patients with inflammatory bowel disease and healthy individuals. J Proteome Res. 2012;11:3344–57.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Sonkar K, Behari A, Kapoor VK, Sinha N. 1H NMR metabolic profiling of human serum associated with benign and malignant gallstone diseases. Metabolomics. 2013;9:515–28.CrossRef Sonkar K, Behari A, Kapoor VK, Sinha N. 1H NMR metabolic profiling of human serum associated with benign and malignant gallstone diseases. Metabolomics. 2013;9:515–28.CrossRef
26.
Zurück zum Zitat Williams HR, Cox IJ, Walker DG, North BV, Patel VM, Marshall SE, et al. Characterization of inflammatory bowel disease with urinary metabolic profiling. Am J Gastroenterol. 2009;104:1435–44.CrossRefPubMed Williams HR, Cox IJ, Walker DG, North BV, Patel VM, Marshall SE, et al. Characterization of inflammatory bowel disease with urinary metabolic profiling. Am J Gastroenterol. 2009;104:1435–44.CrossRefPubMed
27.
Zurück zum Zitat Wasinski F, Gregnani MF, Ornellas FH, Bacurau AVN, et al. Lymphocyte glucose and glutamine metabolism as targets of the anti-inflammatory and immunomodulatory effects of exercise. Mediat Inflamm. 2014;2014:10.CrossRef Wasinski F, Gregnani MF, Ornellas FH, Bacurau AVN, et al. Lymphocyte glucose and glutamine metabolism as targets of the anti-inflammatory and immunomodulatory effects of exercise. Mediat Inflamm. 2014;2014:10.CrossRef
28.
Zurück zum Zitat Khovidhunkit W, Kim M-S, Memon RA, Shigenaga JK, Moser AH, Feingold KR, et al. Thematic review series: the pathogenesis of atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host. J Lipid Res. 2004;45:1169–96.CrossRefPubMed Khovidhunkit W, Kim M-S, Memon RA, Shigenaga JK, Moser AH, Feingold KR, et al. Thematic review series: the pathogenesis of atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host. J Lipid Res. 2004;45:1169–96.CrossRefPubMed
29.
Zurück zum Zitat Watanabe M, Suliman ME, Qureshi AR, Garcia-Lopez E, Bárány P, Heimbürger O, et al. Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality. Am J Clin Nutr. 2008;87:1860–6.PubMed Watanabe M, Suliman ME, Qureshi AR, Garcia-Lopez E, Bárány P, Heimbürger O, et al. Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality. Am J Clin Nutr. 2008;87:1860–6.PubMed
30.
Zurück zum Zitat Nagana Gowda GA, Zhang S, Gu H, Asiago V, Shanaiah N, Raftery D. Metabolomics-based methods for early disease diagnostics: a review. Expert Rev Mol Diagn. 2008;8:617–33.CrossRefPubMedCentral Nagana Gowda GA, Zhang S, Gu H, Asiago V, Shanaiah N, Raftery D. Metabolomics-based methods for early disease diagnostics: a review. Expert Rev Mol Diagn. 2008;8:617–33.CrossRefPubMedCentral
Metadaten
Titel
1H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation
verfasst von
Raj Kumar Sharma
Kumudesh Mishra
Alvina Farooqui
Anu Behari
Vinay Kumar Kapoor
Neeraj Sinha
Publikationsdatum
21.10.2016
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 1/2017
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-016-0998-y

Weitere Artikel der Ausgabe 1/2017

Inflammation Research 1/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.