Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: Identification of Urine Metabolites as Biomarkers of Early Lyme Disease

Abstract

Metabolites detectible in human biofuids are attractive biomarkers for the diagnosis of early Lyme disease (ELD), a vector-borne infectious disease. Urine represents an easily obtained clinical sample that can be applied for diagnostic purposes. However, few studies have explored urine for biomarkers of ELD. In this study, metabolomics approaches were applied to evaluate small molecule metabolites in urine from patients with ELD (n=14), infectious mononucleosis (n=14) and healthy controls (n=14). Metabolic biosignatures for ELD versus healthy controls and ELD versus infectious mononucleosis were generated using untargeted metabolomics. Pathway analyses and metabolite identifcation revealed the dysregulation of several metabolic processes in ELD as compared to healthy controls or mononucleosis, including metabolism of tryptophan. Linear discriminant analyses demonstrated that individual metabolic biosignatures can correctly discriminate ELD from the other patient groups with accuracies of 71 to 100%. These data provide proof-of-concept for use of urine metabolites as biomarkers for diagnostic classifcation of ELD.

Authors:
 [1];  [1];  [2];  [2];  [3];  [4];  [1];  [2];  [1];  [1];  [1]
+ Show Author Affiliations
  1. Centers for Disease Control and Prevention (CDC), Fort Collins, CO (United States). Division of Vector-Borne Diseases
  2. Colorado State Univ., Fort Collins, CO (United States). Dept. of Microbiology
  3. New York Medical College, Valhalla, NY (United States). Dept. of Medicine. Division of Infectious Diseases
  4. Colorado State Univ., Fort Collins, CO (United States). Colorado State Univ. Health Network
Publication Date:
Research Org.:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1624411
Grant/Contract Number:  
SC0014664
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Science & Technology - Other Topics

Citation Formats

Pegalajar-Jurado, Adoracion, Fitzgerald, Bryna L., Islam, M. Nurul, Belisle, John T., Wormser, Gary P., Waller, Kathlene S., Ashton, Laura V., Webb, Kristofor J., Delorey, Mark J., Clark, Rebecca J., and Molins, Claudia R. Identification of Urine Metabolites as Biomarkers of Early Lyme Disease. United States: N. p., 2018. Web. doi:10.1038/s41598-018-29713-y.
Copy to clipboard
Pegalajar-Jurado, Adoracion, Fitzgerald, Bryna L., Islam, M. Nurul, Belisle, John T., Wormser, Gary P., Waller, Kathlene S., Ashton, Laura V., Webb, Kristofor J., Delorey, Mark J., Clark, Rebecca J., & Molins, Claudia R. Identification of Urine Metabolites as Biomarkers of Early Lyme Disease. United States. https://doi.org/10.1038/s41598-018-29713-y
Copy to clipboard
Pegalajar-Jurado, Adoracion, Fitzgerald, Bryna L., Islam, M. Nurul, Belisle, John T., Wormser, Gary P., Waller, Kathlene S., Ashton, Laura V., Webb, Kristofor J., Delorey, Mark J., Clark, Rebecca J., and Molins, Claudia R. Wed . "Identification of Urine Metabolites as Biomarkers of Early Lyme Disease". United States. https://doi.org/10.1038/s41598-018-29713-y. https://www.osti.gov/servlets/purl/1624411.
Copy to clipboard
@article{osti_1624411,
title = {Identification of Urine Metabolites as Biomarkers of Early Lyme Disease},
author = {Pegalajar-Jurado, Adoracion and Fitzgerald, Bryna L. and Islam, M. Nurul and Belisle, John T. and Wormser, Gary P. and Waller, Kathlene S. and Ashton, Laura V. and Webb, Kristofor J. and Delorey, Mark J. and Clark, Rebecca J. and Molins, Claudia R.},
abstractNote = {Metabolites detectible in human biofuids are attractive biomarkers for the diagnosis of early Lyme disease (ELD), a vector-borne infectious disease. Urine represents an easily obtained clinical sample that can be applied for diagnostic purposes. However, few studies have explored urine for biomarkers of ELD. In this study, metabolomics approaches were applied to evaluate small molecule metabolites in urine from patients with ELD (n=14), infectious mononucleosis (n=14) and healthy controls (n=14). Metabolic biosignatures for ELD versus healthy controls and ELD versus infectious mononucleosis were generated using untargeted metabolomics. Pathway analyses and metabolite identifcation revealed the dysregulation of several metabolic processes in ELD as compared to healthy controls or mononucleosis, including metabolism of tryptophan. Linear discriminant analyses demonstrated that individual metabolic biosignatures can correctly discriminate ELD from the other patient groups with accuracies of 71 to 100%. These data provide proof-of-concept for use of urine metabolites as biomarkers for diagnostic classifcation of ELD.},
doi = {10.1038/s41598-018-29713-y},
journal = {Scientific Reports},
number = 1,
volume = 8,
place = {United States},
year = {Wed Aug 15 00:00:00 EDT 2018},
month = {Wed Aug 15 00:00:00 EDT 2018}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1038/s41598-018-29713-y
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal

Figures / Tables:

Figure 1 Figure 1: Level 1 identification and abundance confirmation of creatinine. Structural identification of creatinine (a,b) and creatinine levels (c). Structural identification was achieved by RT alignment (a) of authentic standard (top panel), the targeted metabolite in pooled urine (middle panel) and authentic standard spiked in pooled patient urine (bottom panel);more » and by comparison of MS/MS spectra (b) of the authentic standard (top panel) and the targeted metabolite in patient urine (bottom panel). Log2 LC-MS median abundances in HC, ELD and MONO are shown for creatinine as triangles (c). Creatinine concentration measured by the alkaline picrate assay are also shown in (c) as squares. HC are shown in blue, ELD in green and MONO in orange. For both measurement types, the mean and standard deviation from the mean are shown.« less
All figures and tables (7 total)
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

Incidence of Clinician-Diagnosed Lyme Disease, United States, 2005–2010
journal, September 2015

  • Nelson, Christina A.; Saha, Shubhayu; Kugeler, Kiersten J.
  • Emerging Infectious Diseases, Vol. 21, Issue 9
  • DOI: 10.3201/eid2109.150417

Metabolic Response to Infection
journal, February 1975

Metabolic Response to Infection
journal, February 1975

A robust modification of the ordered-heterogeneity test
journal, August 2006

A robust modification of the ordered-heterogeneity test
journal, August 2006

MetaboAnalyst 3.0—making metabolomics more meaningful
journal, April 2015

  • Xia, Jianguo; Sinelnikov, Igor V.; Han, Beomsoo
  • Nucleic Acids Research, Vol. 43, Issue W1
  • DOI: 10.1093/nar/gkv380

MetaboAnalyst 3.0—making metabolomics more meaningful
journal, April 2015

  • Xia, Jianguo; Sinelnikov, Igor V.; Han, Beomsoo
  • Nucleic Acids Research, Vol. 43, Issue W1
  • DOI: 10.1093/nar/gkv380

Early Lyme Disease
journal, June 2006

High frequency of false positive IgM immunoblots for Borrelia burgdorferi in Clinical Practice
journal, December 2012

Southern Tick-Associated Rash Illness (STARI) in the North: STARI Following a Tick Bite in Long Island, New York
journal, September 2011

  • Feder, H. M.; Hoss, D. M.; Zemel, L.
  • Clinical Infectious Diseases, Vol. 53, Issue 10
  • DOI: 10.1093/cid/cir553

Southern Tick-Associated Rash Illness (STARI) in the North: STARI Following a Tick Bite in Long Island, New York
journal, September 2011

  • Feder, H. M.; Hoss, D. M.; Zemel, L.
  • Clinical Infectious Diseases, Vol. 53, Issue 10
  • DOI: 10.1093/cid/cir553

High frequency of false positive IgM immunoblots for Borrelia burgdorferi in Clinical Practice
journal, December 2012

Serodiagnosis of Early Lyme Disease: Analysis of IgM and IgG Antibody Responses by Using an Antibody-Capture Enzyme Immunoassay
journal, October 1988

  • Berardi, Victor P.; Weeks, Karen E.; Steere, Allen C.
  • The Journal of Infectious Diseases, Vol. 158, Issue 4
  • DOI: 10.1093/infdis/158.4.754

HMDB: a knowledgebase for the human metabolome
journal, January 2009

  • Wishart, D. S.; Knox, C.; Guo, A. C.
  • Nucleic Acids Research, Vol. 37, Issue Database
  • DOI: 10.1093/nar/gkn810

Serodiagnosis of Early Lyme Disease: Analysis of IgM and IgG Antibody Responses by Using an Antibody-Capture Enzyme Immunoassay
journal, October 1988

  • Berardi, Victor P.; Weeks, Karen E.; Steere, Allen C.
  • The Journal of Infectious Diseases, Vol. 158, Issue 4
  • DOI: 10.1093/infdis/158.4.754

MetaboAnalyst: a web server for metabolomic data analysis and interpretation
journal, May 2009

  • Xia, J.; Psychogios, N.; Young, N.
  • Nucleic Acids Research, Vol. 37, Issue Web Server
  • DOI: 10.1093/nar/gkp356

Effect of creatinine and specific gravity normalization on urinary biomarker 1,6-hexamethylene diamine
journal, January 2010

  • Gaines, Linda G. T.; Fent, Kenneth W.; Flack, Sheila L.
  • Journal of Environmental Monitoring, Vol. 12, Issue 3
  • DOI: 10.1039/b921073c

Current and Future Applications of Mass Spectrometry to the Clinical Laboratory
journal, October 2011

  • Strathmann, Frederick G.; Hoofnagle, Andrew N.
  • American Journal of Clinical Pathology, Vol. 136, Issue 4
  • DOI: 10.1309/ajcpw0ta8obbngck

Lyme borreliosis
journal, February 2012

The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America
journal, November 2006

  • Wormser, Gary P.; Dattwyler, Raymond J.; Shapiro, Eugene D.
  • Clinical Infectious Diseases, Vol. 43, Issue 9
  • DOI: 10.1086/508667

The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population
journal, May 2010

  • Wagner, Brandie D.; Accurso, Frank J.; Laguna, Theresa A.
  • Journal of Cystic Fibrosis, Vol. 9, Issue 3
  • DOI: 10.1016/j.jcf.2010.02.004

Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-Barr Virus Infection: Report of 2 Cases
journal, April 2017

  • Pavletic, Adriana J.; Marques, Adriana R.
  • Clinical Infectious Diseases, Vol. 65, Issue 2
  • DOI: 10.1093/cid/cix298

Systematic impacts of chronic unpredictable mild stress on metabolomics in rats
journal, January 2020

Lyme Disease: Laboratory Issues
journal, June 2008

HMDB: a knowledgebase for the human metabolome
journal, January 2009

  • Wishart, D. S.; Knox, C.; Guo, A. C.
  • Nucleic Acids Research, Vol. 37, Issue Database
  • DOI: 10.1093/nar/gkn810

Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms
journal, July 2011

Critical Evaluation of Urine-Based PCR Assay for Diagnosis of Lyme Borreliosis
journal, August 2005

Normalization strategies for metabonomic analysis of urine samples
journal, February 2009

Phenotypic Characterization Analysis of Human Hepatocarcinoma by Urine Metabolomics Approach
journal, January 2016

  • Liang, Qun; Liu, Han; Wang, Cong
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep19763

Application of Nanotrap technology for high sensitivity measurement of urinary outer surface protein A carboxyl-terminus domain in early stage Lyme borreliosis
journal, November 2015

  • Magni, Ruben; Espina, Benjamin H.; Shah, Ketul
  • Journal of Translational Medicine, Vol. 13, Issue 1
  • DOI: 10.1186/s12967-015-0701-z

Application of Nanotrap technology for high sensitivity measurement of urinary outer surface protein A carboxyl-terminus domain in early stage Lyme borreliosis
journal, November 2015

  • Magni, Ruben; Espina, Benjamin H.; Shah, Ketul
  • Journal of Translational Medicine, Vol. 13, Issue 1
  • DOI: 10.1186/s12967-015-0701-z

A metabolic biosignature of early response to anti-tuberculosis treatment
journal, January 2014

  • Mahapatra, Sebabrata; Hess, Ann M.; Johnson, John L.
  • BMC Infectious Diseases, Vol. 14, Issue 1
  • DOI: 10.1186/1471-2334-14-53

Measurement of urinary concentration: a critical appraisal of methodologies
journal, April 2001

  • Chadha, Vimal; Alon, U. S.; Garg, Uttam
  • Pediatric Nephrology, Vol. 16, Issue 4
  • DOI: 10.1007/s004670000551

Prostate Cancer Patients–Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics
journal, December 2016

  • Fernández-Peralbo, M. A.; Gómez-Gómez, E.; Calderón-Santiago, M.
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep38243

Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients
journal, May 2015

  • Armstrong, Christopher W.; McGregor, Neil R.; Lewis, Donald P.
  • Metabolomics, Vol. 11, Issue 6
  • DOI: 10.1007/s11306-015-0816-5

Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling
journal, November 2017

  • Marques, Adriana; Schwartz, Ira; Wormser, Gary P.
  • The Journal of Infectious Diseases, Vol. 217, Issue 1
  • DOI: 10.1093/infdis/jix563

Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-Barr Virus Infection: Report of 2 Cases
journal, April 2017

  • Pavletic, Adriana J.; Marques, Adriana R.
  • Clinical Infectious Diseases, Vol. 65, Issue 2
  • DOI: 10.1093/cid/cix298

Metabolic differentiation of early Lyme disease from southern tick–associated rash illness (STARI)
journal, August 2017

  • Molins, Claudia R.; Ashton, Laura V.; Wormser, Gary P.
  • Science Translational Medicine, Vol. 9, Issue 403
  • DOI: 10.1126/scitranslmed.aal2717

Deregulated Tyrosine–Phenylalanine Metabolism in Pulmonary Tuberculosis Patients
journal, March 2015

Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms
journal, July 2011

Erythema Migrans
journal, June 2015

Erythema Migrans
journal, June 2008

  • Dandache, Patricia; Nadelman, Robert B.
  • Infectious Disease Clinics of North America, Vol. 22, Issue 2
  • DOI: 10.1016/j.idc.2007.12.012

The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America
journal, November 2006

  • Wormser, Gary P.; Dattwyler, Raymond J.; Shapiro, Eugene D.
  • Clinical Infectious Diseases, Vol. 43, Issue 9
  • DOI: 10.1086/508667

Epstein-barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early lyme borreliosis
journal, May 1999

  • Goossens, H. A. T.; van den Bogaard, A. E. J. M.; Nohlmans, M. K. E.
  • Infection, Vol. 27, Issue 3
  • DOI: 10.1007/BF02561539

Local Generation of Kynurenines Mediates Inhibition of Neutrophil Chemotaxis by Uropathogenic Escherichia coli
journal, February 2016

  • Loughman, Jennifer A.; Yarbrough, Melanie L.; Tiemann, Kristin M.
  • Infection and Immunity, Vol. 84, Issue 4
  • DOI: 10.1128/iai.01202-15

Tyrosine metabolism during interferon-alpha administration: Association with fatigue and CSF dopamine concentrations
journal, July 2013

Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report
journal, December 2017

In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans
journal, April 2016

Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients
journal, May 2015

  • Armstrong, Christopher W.; McGregor, Neil R.; Lewis, Donald P.
  • Metabolomics, Vol. 11, Issue 6
  • DOI: 10.1007/s11306-015-0816-5

Erythema Migrans
journal, June 2008

  • Dandache, Patricia; Nadelman, Robert B.
  • Infectious Disease Clinics of North America, Vol. 22, Issue 2
  • DOI: 10.1016/j.idc.2007.12.012

Global metabolic profiling procedures for urine using UPLC–MS
journal, May 2010

  • Want, Elizabeth J.; Wilson, Ian D.; Gika, Helen
  • Nature Protocols, Vol. 5, Issue 6
  • DOI: 10.1038/nprot.2010.50

Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics☆
journal, May 2009

  • Kitteringham, Neil R.; Jenkins, Rosalind E.; Lane, Catherine S.
  • Journal of Chromatography B, Vol. 877, Issue 13
  • DOI: 10.1016/j.jchromb.2008.11.013

Deregulated Tyrosine–Phenylalanine Metabolism in Pulmonary Tuberculosis Patients
journal, March 2015

Measurement of urinary concentration: a critical appraisal of methodologies
journal, April 2001

  • Chadha, Vimal; Alon, U. S.; Garg, Uttam
  • Pediatric Nephrology, Vol. 16, Issue 4
  • DOI: 10.1007/s004670000551

Activity of selected aromatic amino acids in biological systems.
journal, December 2011

Mass appeal: metabolite identification in mass spectrometry-focused untargeted metabolomics
journal, May 2012

Mass appeal: metabolite identification in mass spectrometry-focused untargeted metabolomics
journal, May 2012

A metabolic biosignature of early response to anti-tuberculosis treatment
journal, January 2014

  • Mahapatra, Sebabrata; Hess, Ann M.; Johnson, John L.
  • BMC Infectious Diseases, Vol. 14, Issue 1
  • DOI: 10.1186/1471-2334-14-53

Indoleamine 2,3-dioxygenase–expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection
journal, December 2006

  • Popov, Alexey; Abdullah, Zeinab; Wickenhauser, Claudia
  • Journal of Clinical Investigation, Vol. 116, Issue 12
  • DOI: 10.1172/jci28996

Detection of antigens in urine of mice and humans infected with Borrelia burgdorferi, etiologic agent of Lyme disease
journal, January 1989

Normalization strategies for metabonomic analysis of urine samples
journal, February 2009

Collection and Characterization of Samples for Establishment of a Serum Repository for Lyme Disease Diagnostic Test Development and Evaluation
journal, August 2014

  • Molins, C. R.; Sexton, C.; Young, J. W.
  • Journal of Clinical Microbiology, Vol. 52, Issue 10
  • DOI: 10.1128/jcm.01409-14

Erythema Migrans
journal, June 2015

Prostate Cancer Patients–Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics
journal, December 2016

  • Fernández-Peralbo, M. A.; Gómez-Gómez, E.; Calderón-Santiago, M.
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep38243

Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics☆
journal, May 2009

  • Kitteringham, Neil R.; Jenkins, Rosalind E.; Lane, Catherine S.
  • Journal of Chromatography B, Vol. 877, Issue 13
  • DOI: 10.1016/j.jchromb.2008.11.013

Normalization of urinary biomarkers to creatinine during changes in glomerular filtration rate
journal, September 2010

  • Waikar, Sushrut S.; Sabbisetti, Venkata S.; Bonventre, Joseph V.
  • Kidney International, Vol. 78, Issue 5
  • DOI: 10.1038/ki.2010.165

Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report
journal, December 2017

Phenylalanine and Tyrosine Metabolism in Chronic Kidney Failure
journal, June 2007

In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans
journal, April 2016

Tyrosine metabolism during interferon-alpha administration: Association with fatigue and CSF dopamine concentrations
journal, July 2013

The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population
journal, May 2010

  • Wagner, Brandie D.; Accurso, Frank J.; Laguna, Theresa A.
  • Journal of Cystic Fibrosis, Vol. 9, Issue 3
  • DOI: 10.1016/j.jcf.2010.02.004

Induction of indoleamine 2,3-dioxygenase by Borrelia burgdorferi in human immune cells correlates with pathogenic potential
journal, November 2014

  • Love, Andrea C.; Schwartz, Ira; Petzke, Mary M.
  • Journal of Leukocyte Biology, Vol. 97, Issue 2
  • DOI: 10.1189/jlb.4a0714-339r

Lyme Disease Testing by Large Commercial Laboratories in the United States
journal, May 2014

  • Hinckley, Alison F.; Connally, Neeta P.; Meek, James I.
  • Clinical Infectious Diseases, Vol. 59, Issue 5
  • DOI: 10.1093/cid/ciu397

Immunoblot interpretation criteria for serodiagnosis of early Lyme disease
journal, February 1995

Development of a Metabolic Biosignature for Detection of Early Lyme Disease
journal, March 2015

  • Molins, Claudia R.; Ashton, Laura V.; Wormser, Gary P.
  • Clinical Infectious Diseases, Vol. 60, Issue 12
  • DOI: 10.1093/cid/civ185

Detection of antigens in urine of mice and humans infected with Borrelia burgdorferi, etiologic agent of Lyme disease
journal, January 1989

Metabolic features of chronic fatigue syndrome
journal, August 2016

  • Naviaux, Robert K.; Naviaux, Jane C.; Li, Kefeng
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 37
  • DOI: 10.1073/pnas.1607571113
    Sort by:
    [ × clear filter / sort ]

    Figures / Tables found in this record:

    Figure 1 (p. 3)figure
    Figure 2 (p. 4)figure
    Figure 3 (p. 5)figure
    Figure 4 (p. 6)figure
    Figure 5 (p. 7)figure
    Table 1 (p. 7)table
    Table 2 (p. 8)table
      [ × clear filter / sort ]
      Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.

      Similar Records in DOE PAGES and OSTI.GOV collections: