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Comprehensive 1H NMR metabolic profiling of body fluids for differentiation of meningitis in adults

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Abstract

Introduction

Meningitis, a morbidly infectious central nervous system pathology is accompanied by acute inflammation of the meninges, causing raised intracranial pressure linked with serious neurological sequelae.

Objective

To observe the variation in the metabolic profile, that may occur in serum and urine along with CSF in adults using 1H NMR spectroscopy, with an attempt of appropriate and timely treatment regimen.

Methods

The 1H NMR-based metabolomics has been performed in 115 adult subjects for differentiating bacterial meningitis (BM) and tubercular meningitis (TBM).

Results

The discriminant function analysis (DFA) of the three bio-fluids collectively identified 3-hydroxyisovalerate, lactate, glucose, formate, valine, alanine, ketonic bodies, malonate and choline containing compounds (choline and GPC) as significant metabolites among cases versus control group. The differentiation of bacterial meningitis and tuberculous meningitis (BM vs. TBM) can be done on the basis of identification of 3-hydroxyisovalerate, isobutyrate and formate in case of CSF (with a correct classification of 78 %), alanine in serum (correct classification 60 %), valine and acetone in case of urine (correct classification 89.1 %). The NMR spectral bins based orthogonal signal correction principal component analysis score plots of significant metabolites obtained from DFA also provided group classification among cases versus control group in CSF, serum and urine samples. The variable importance in projection scores also identified similar significant metabolites as obtained from DFA, collectively in CSF, serum and urine samples, responsible for differentiation of meningitis.

Conclusion

The CSF contained metabolites which are formed during infection and inflammation, and these were also found in significant quantity in serum and urine samples.

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Abbreviations

BM:

Bacterial meningitis/pyogenic meningitis

CPMG:

Carr-purcell-meiboom-gill

CSF:

Cerebrospinal fluid

CT:

Computed tomography

DFA:

Discriminant function analysis

FDR:

False discovery rate

MRI:

Magnetic resonance imaging

NMR:

Nuclear magnetic resonance

NOESY:

Nuclear overhauser effect spectroscopy

OSC-PCA:

Orthogonal signal correction-principal component analysis

PLS-DA:

Partial least square discriminant analysis

SD:

Standard deviation

TBM:

Tubercular meningitis

TSP:

Trimethylsilyl propionate

VIP:

Variables importance in projection

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Acknowledgments

The authors are thankful to Dr. Ram Manohar Lohia Institute of Medical Sciences for intramural funding (IEC 14/11) to carry out the study and Centre of Biomedical Research, Lucknow where the 1H NMR spectroscopy was conducted. Dr. Suruchi Singh would like to extend her thanks to Council of Scientific and Industrial Research (RA Award No.: 09/916/(0077)/2013/EMR-I) for financial assistance.

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    Authors and Affiliations

    1. Department of Microbiology, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow, 226010, India

      Tanushri Chatterji & Manodeep Sen

    2. Department of Neurology, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow, 226010, India

      Ajai Kumar Singh & Pradeep Kumar Maurya

    3. Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow, 226010, India

      Nuzhat Husain

    4. Centre of Biomedical Research, Formerly Centre of Biomedical Magnetic Resonance (CBMR), Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Rae Bareli Road, Lucknow, 226014, India

      Suruchi Singh, Sudhir Kumar Mandal & Raja Roy

    5. Amity Institute of Biotechnology, Amity University Uttar Pradesh, Malhaur, Lucknow, 226028, India

      Tanushri Chatterji & Janmejai Kumar Srivastava

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    1. Tanushri Chatterji
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    The authors have no potential conflict of interest. The disclosure of potential conflict of interest in the prescribed format has been obtained from all the authors.

    Ethical approval

    The study was ethically approved and the work was performed in strict accordance with the guidelines of Institutional Ethical Committee of Dr. Ram Manohar Lohia Institute of Medical Sciences (IEC 14/11).

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    The subjects were explained the study procedure and written and informed consent were obtained from them prior to the study. The authors: Tanushri Chatterji, Suruchi Singh, Manodeep Sen, Ajai Kumar Singh, Pradeep Kumar Maurya, Nuzhat Husain, Janmejai Kumar Srivastava, Sudhir Kumar Mandal, and Raja Roy are aware of ethical policy.

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    Tanushri Chatterji and Suruchi Singh have contributed equally.

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    Chatterji, T., Singh, S., Sen, M. et al. Comprehensive 1H NMR metabolic profiling of body fluids for differentiation of meningitis in adults. Metabolomics 12, 130 (2016). https://doi.org/10.1007/s11306-016-1073-y

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