Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer. 2004;4:695–706.

    Article  CAS  PubMed  Google Scholar 

  2. Silk YN, Douglass HO, Nava HR, Driscoll DL, Tartarian G. Carcinoma of the gallbladder. The Roswell Park experience. Ann Surg. 1989;210:751–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. Maurer KJ, Carey MC, Fox JG. Roles of infection, inflammation, and the immune system in cholesterol gallstone formation. Gastroenterology. 2009;136:425–40.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. van Erpecum KJ. Biliary lipids, water and cholesterol gallstones. Biol Cell. 2005;97:815–22.

    Article  PubMed  Google Scholar 

  8. 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.

    Chapter  Google Scholar 

  9. Behar J. Physiology and pathophysiology of the biliary tract: the gallbladder and sphincter of Oddi—A review. ISRN Physiol. 2013;2013:15.

    Article  Google Scholar 

  10. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. Chen Z, Kim J. Urinary proteomics and metabolomics studies to monitor bladder health and urological diseases. BMC Urol. 2016;16:016–0129.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. 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. 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. 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.

    CAS  PubMed  Google Scholar 

  19. 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.

    Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 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.

    Google Scholar 

  24. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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.

    Article  CAS  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    CAS  PubMed  Google Scholar 

  30. 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.

    Article  PubMed Central  Google Scholar 

Download references

Acknowledgments

We acknowledge financial support from Department of Science and Technology (Grant Number EMR/2015/001758).

Author information

Authors and Affiliations

  1. Centre of Biomedical Research, SGPGIMS Campus, Lucknow, 226014, India

    Raj Kumar Sharma & Neeraj Sinha

  2. Department of Biosciences, Integral University, Kursi Road, Lucknow, 226026, India

    Raj Kumar Sharma & Alvina Farooqui

  3. Department of Surgical Gastroenterology, SGPGIMS, Lucknow, 226014, India

    Kumudesh Mishra, Anu Behari & Vinay Kumar Kapoor

Authors
  1. Raj Kumar Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kumudesh Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alvina Farooqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anu Behari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vinay Kumar Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Neeraj Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neeraj Sinha.

Additional information

Responsible Editor: John Di Battista.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Two-dimensional (2D) spectrum are given as supporting information (DOCX 1175 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharma, R.K., Mishra, K., Farooqui, A. et al. 1H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation. Inflamm. Res. 66, 97–105 (2017). https://doi.org/10.1007/s00011-016-0998-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-016-0998-y

Keywords

Search

Navigation