Serum and urine metabolomic fngerprinting in diagnostics of inflammatory bowel diseases

Tomasz Dawiskiba, Stanisław Deja, Agata Mulak, Adam Zabek, Ewa Jawień, Dorota Pawełka, Mirosław Banasik, Agnieszka Mastalerz-Migas, Waldemar Balcerzak, Krzysztof Kaliszewski, Jan Skóra, Piotr Barć, Krzysztof Korta, Kornel Pormańczuk, Przemyslaw Szyber, Adam Litarski, Piotr Młynarz

Research output: Contribution to journalArticle

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Abstract

AIM: To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases (IBD). METHODS: Serum and urine samples were collected from 24 patients with ulcerative colitis (UC), 19 patients with the Crohn's disease (CD) and 17 healthy controls. The activity of UC was assessed with the Simple Clinical Colitis Activity Index, while the activity of CD was determined using the Harvey-Bradshaw Index. The analysis of serum and urine samples was performed using proton nuclear magnetic resonance (NMR) spectroscopy. All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine. Prior to the chemometric analysis, both data sets were unit variance scaled. The differences in metabolite fingerprints were assessed using partial least-squares-discriminant analysis (PLS-DA). Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models. Metabolites responsible for separation in models were tested using STATISTICA 10 with the Mann-Whitney-Wilcoxon test and the Student's t test (α = 0.05). RESULTS: The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models (P value 0.002 for serum and 0.003 for urine). The metabolites that allowed to distinguish these groups were: N-acetylated compounds and phenylalanine (up-regulated in serum), low-density lipoproteins and very low-density lipopro-teins (decreased in serum) as well as glycine (increased in urine) and acetoacetate (decreased in urine). The signifcant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation (P value < 0.001 for serum and 0.003 for urine). The metabolites that were found to be the strongest biomarkers included in this case: leucine, isoleucine, 3-hydroxybutyric acid, N-acet-ylated compounds, acetoacetate, glycine, phenylalanine and lactate (increased in serum), creatine, dimethyl sul-fone, histidine, choline and its derivatives (decreased in serum), as well as citrate, hippurate, trigonelline, tau-rine, succinate and 2-hydroxyisobutyrate (decreased in urine). No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples, although one metabolite (formate) in univariate statistical analysis was signif-cantly lower in serum of patients with active CD, and two metabolites (alanine and N-acetylated compounds) were signifcantly higher in serum of patients with CD when comparing jointly patients in the remission and active phase of the diseases. Contrary to the results obtained from the serum samples, the analysis of urine samples allowed to distinguish patients with IBD in remission from healthy control subjects. The metabolites of importance included in this case up-regulated aceto-acetate and down-regulated citrate, hippurate, taurine, succinate, glycine, alanine and formate. CONCLUSION: NMR-based metabolomic fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.

Original languageEnglish (US)
Pages (from-to)163-174
Number of pages12
JournalWorld Journal of Gastroenterology
Volume20
Issue number1
DOIs
StatePublished - Jan 7 2014
Externally publishedYes

Fingerprint

Metabolomics
Inflammatory Bowel Diseases
Urine
Serum
Discriminant Analysis
Least-Squares Analysis
formic acid
Crohn Disease
Ulcerative Colitis
Glycine
VLDL Lipoproteins
Succinic Acid
Phenylalanine
Citric Acid
Alanine
Healthy Volunteers
Magnetic Resonance Spectroscopy
3-Hydroxybutyric Acid
Creatine
Isoleucine

Keywords

  • Crohn's disease
  • Inflammatory bowel disease
  • Metabolomics
  • Partial least-squares-discriminant analysis
  • Proton nuclear magnetic resonance spectroscopy
  • Serum
  • Ulcerative colitis
  • Urine

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Serum and urine metabolomic fngerprinting in diagnostics of inflammatory bowel diseases. / Dawiskiba, Tomasz; Deja, Stanisław; Mulak, Agata; Zabek, Adam; Jawień, Ewa; Pawełka, Dorota; Banasik, Mirosław; Mastalerz-Migas, Agnieszka; Balcerzak, Waldemar; Kaliszewski, Krzysztof; Skóra, Jan; Barć, Piotr; Korta, Krzysztof; Pormańczuk, Kornel; Szyber, Przemyslaw; Litarski, Adam; Młynarz, Piotr.

In: World Journal of Gastroenterology, Vol. 20, No. 1, 07.01.2014, p. 163-174.

Research output: Contribution to journalArticle

Dawiskiba, T, Deja, S, Mulak, A, Zabek, A, Jawień, E, Pawełka, D, Banasik, M, Mastalerz-Migas, A, Balcerzak, W, Kaliszewski, K, Skóra, J, Barć, P, Korta, K, Pormańczuk, K, Szyber, P, Litarski, A & Młynarz, P 2014, 'Serum and urine metabolomic fngerprinting in diagnostics of inflammatory bowel diseases', World Journal of Gastroenterology, vol. 20, no. 1, pp. 163-174. https://doi.org/10.3748/wjg.v20.i1.163
Dawiskiba, Tomasz ; Deja, Stanisław ; Mulak, Agata ; Zabek, Adam ; Jawień, Ewa ; Pawełka, Dorota ; Banasik, Mirosław ; Mastalerz-Migas, Agnieszka ; Balcerzak, Waldemar ; Kaliszewski, Krzysztof ; Skóra, Jan ; Barć, Piotr ; Korta, Krzysztof ; Pormańczuk, Kornel ; Szyber, Przemyslaw ; Litarski, Adam ; Młynarz, Piotr. / Serum and urine metabolomic fngerprinting in diagnostics of inflammatory bowel diseases. In: World Journal of Gastroenterology. 2014 ; Vol. 20, No. 1. pp. 163-174.
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abstract = "AIM: To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases (IBD). METHODS: Serum and urine samples were collected from 24 patients with ulcerative colitis (UC), 19 patients with the Crohn's disease (CD) and 17 healthy controls. The activity of UC was assessed with the Simple Clinical Colitis Activity Index, while the activity of CD was determined using the Harvey-Bradshaw Index. The analysis of serum and urine samples was performed using proton nuclear magnetic resonance (NMR) spectroscopy. All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine. Prior to the chemometric analysis, both data sets were unit variance scaled. The differences in metabolite fingerprints were assessed using partial least-squares-discriminant analysis (PLS-DA). Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models. Metabolites responsible for separation in models were tested using STATISTICA 10 with the Mann-Whitney-Wilcoxon test and the Student's t test (α = 0.05). RESULTS: The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models (P value 0.002 for serum and 0.003 for urine). The metabolites that allowed to distinguish these groups were: N-acetylated compounds and phenylalanine (up-regulated in serum), low-density lipoproteins and very low-density lipopro-teins (decreased in serum) as well as glycine (increased in urine) and acetoacetate (decreased in urine). The signifcant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation (P value < 0.001 for serum and 0.003 for urine). The metabolites that were found to be the strongest biomarkers included in this case: leucine, isoleucine, 3-hydroxybutyric acid, N-acet-ylated compounds, acetoacetate, glycine, phenylalanine and lactate (increased in serum), creatine, dimethyl sul-fone, histidine, choline and its derivatives (decreased in serum), as well as citrate, hippurate, trigonelline, tau-rine, succinate and 2-hydroxyisobutyrate (decreased in urine). No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples, although one metabolite (formate) in univariate statistical analysis was signif-cantly lower in serum of patients with active CD, and two metabolites (alanine and N-acetylated compounds) were signifcantly higher in serum of patients with CD when comparing jointly patients in the remission and active phase of the diseases. Contrary to the results obtained from the serum samples, the analysis of urine samples allowed to distinguish patients with IBD in remission from healthy control subjects. The metabolites of importance included in this case up-regulated aceto-acetate and down-regulated citrate, hippurate, taurine, succinate, glycine, alanine and formate. CONCLUSION: NMR-based metabolomic fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.",
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T1 - Serum and urine metabolomic fngerprinting in diagnostics of inflammatory bowel diseases

AU - Dawiskiba, Tomasz

AU - Deja, Stanisław

AU - Mulak, Agata

AU - Zabek, Adam

AU - Jawień, Ewa

AU - Pawełka, Dorota

AU - Banasik, Mirosław

AU - Mastalerz-Migas, Agnieszka

AU - Balcerzak, Waldemar

AU - Kaliszewski, Krzysztof

AU - Skóra, Jan

AU - Barć, Piotr

AU - Korta, Krzysztof

AU - Pormańczuk, Kornel

AU - Szyber, Przemyslaw

AU - Litarski, Adam

AU - Młynarz, Piotr

PY - 2014/1/7

Y1 - 2014/1/7

N2 - AIM: To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases (IBD). METHODS: Serum and urine samples were collected from 24 patients with ulcerative colitis (UC), 19 patients with the Crohn's disease (CD) and 17 healthy controls. The activity of UC was assessed with the Simple Clinical Colitis Activity Index, while the activity of CD was determined using the Harvey-Bradshaw Index. The analysis of serum and urine samples was performed using proton nuclear magnetic resonance (NMR) spectroscopy. All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine. Prior to the chemometric analysis, both data sets were unit variance scaled. The differences in metabolite fingerprints were assessed using partial least-squares-discriminant analysis (PLS-DA). Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models. Metabolites responsible for separation in models were tested using STATISTICA 10 with the Mann-Whitney-Wilcoxon test and the Student's t test (α = 0.05). RESULTS: The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models (P value 0.002 for serum and 0.003 for urine). The metabolites that allowed to distinguish these groups were: N-acetylated compounds and phenylalanine (up-regulated in serum), low-density lipoproteins and very low-density lipopro-teins (decreased in serum) as well as glycine (increased in urine) and acetoacetate (decreased in urine). The signifcant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation (P value < 0.001 for serum and 0.003 for urine). The metabolites that were found to be the strongest biomarkers included in this case: leucine, isoleucine, 3-hydroxybutyric acid, N-acet-ylated compounds, acetoacetate, glycine, phenylalanine and lactate (increased in serum), creatine, dimethyl sul-fone, histidine, choline and its derivatives (decreased in serum), as well as citrate, hippurate, trigonelline, tau-rine, succinate and 2-hydroxyisobutyrate (decreased in urine). No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples, although one metabolite (formate) in univariate statistical analysis was signif-cantly lower in serum of patients with active CD, and two metabolites (alanine and N-acetylated compounds) were signifcantly higher in serum of patients with CD when comparing jointly patients in the remission and active phase of the diseases. Contrary to the results obtained from the serum samples, the analysis of urine samples allowed to distinguish patients with IBD in remission from healthy control subjects. The metabolites of importance included in this case up-regulated aceto-acetate and down-regulated citrate, hippurate, taurine, succinate, glycine, alanine and formate. CONCLUSION: NMR-based metabolomic fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.

AB - AIM: To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases (IBD). METHODS: Serum and urine samples were collected from 24 patients with ulcerative colitis (UC), 19 patients with the Crohn's disease (CD) and 17 healthy controls. The activity of UC was assessed with the Simple Clinical Colitis Activity Index, while the activity of CD was determined using the Harvey-Bradshaw Index. The analysis of serum and urine samples was performed using proton nuclear magnetic resonance (NMR) spectroscopy. All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine. Prior to the chemometric analysis, both data sets were unit variance scaled. The differences in metabolite fingerprints were assessed using partial least-squares-discriminant analysis (PLS-DA). Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models. Metabolites responsible for separation in models were tested using STATISTICA 10 with the Mann-Whitney-Wilcoxon test and the Student's t test (α = 0.05). RESULTS: The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models (P value 0.002 for serum and 0.003 for urine). The metabolites that allowed to distinguish these groups were: N-acetylated compounds and phenylalanine (up-regulated in serum), low-density lipoproteins and very low-density lipopro-teins (decreased in serum) as well as glycine (increased in urine) and acetoacetate (decreased in urine). The signifcant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation (P value < 0.001 for serum and 0.003 for urine). The metabolites that were found to be the strongest biomarkers included in this case: leucine, isoleucine, 3-hydroxybutyric acid, N-acet-ylated compounds, acetoacetate, glycine, phenylalanine and lactate (increased in serum), creatine, dimethyl sul-fone, histidine, choline and its derivatives (decreased in serum), as well as citrate, hippurate, trigonelline, tau-rine, succinate and 2-hydroxyisobutyrate (decreased in urine). No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples, although one metabolite (formate) in univariate statistical analysis was signif-cantly lower in serum of patients with active CD, and two metabolites (alanine and N-acetylated compounds) were signifcantly higher in serum of patients with CD when comparing jointly patients in the remission and active phase of the diseases. Contrary to the results obtained from the serum samples, the analysis of urine samples allowed to distinguish patients with IBD in remission from healthy control subjects. The metabolites of importance included in this case up-regulated aceto-acetate and down-regulated citrate, hippurate, taurine, succinate, glycine, alanine and formate. CONCLUSION: NMR-based metabolomic fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.

KW - Crohn's disease

KW - Inflammatory bowel disease

KW - Metabolomics

KW - Partial least-squares-discriminant analysis

KW - Proton nuclear magnetic resonance spectroscopy

KW - Serum

KW - Ulcerative colitis

KW - Urine

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