Characterization of inflammatory bowel disease with urinary metabolic profiling

Horace R. T. Williams; I. Jane Cox; David G. Walker; Bernard V. North; Venisha M. Patel; Sara E. Marshall; Derek P. Jewell; Subrata Ghosh; Huw J. W. Thomas; Julian P. Teare; Simon Jakobovits; Sebastian Zeki; Kenneth I. Welsh; Simon D. Taylor-Robinson; Timothy R. Orchard

doi:10.1038/ajg.2009.175

Characterization of inflammatory bowel disease with urinary metabolic profiling

Horace R. T. Williams, I. Jane Cox, David G. Walker, Bernard V. North, Venisha M. Patel, Sara E. Marshall, Derek P. Jewell, Subrata Ghosh, Huw J. W. Thomas, Julian P. Teare, Simon Jakobovits, Sebastian Zeki, Kenneth I. Welsh, Simon D. Taylor-Robinson, Timothy R. Orchard

Research output: Contribution to journal › Article › peer-review

155 Citations (Scopus)

Abstract

OBJECTIVES: Distinguishing between the inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) is important for both management and prognostic reasons. Discrimination using noninvasive techniques could be an adjunct to conventional diagnostics. Differences have been shown between the intestinal microbiota of CD and UC patients and controls; the gut bacteria influence specific urinary metabolites that are quantifiable using proton highresolution nuclear magnetic resonance (NMR) spectroscopy. This study tested the hypothesis that such metabolites differ between IBD and control cohorts, and that using multivariate pattern-recognition analysis, the cohorts could be distinguished by urine NMR spectroscopy.

METHODS: NMR spectra were acquired from urine samples of 206 Caucasian subjects (86 CD patients, 60 UC patients, and 60 healthy controls). Longitudinal samples were collected from 75 individuals. NMR resonances specific for metabolites influenced by the gut microbes were studied, including hippurate, formate, and 4-cresol sulfate. Multivariate analysis of all urinary metabolites involved principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA).

RESULTS: Hippurate levels were lowest in CD patients and differed significantly between the three cohorts (P<0.0001). Formate levels were higher and 4-cresol sulfate levels lower in CD patients than in UC patients or controls (P=0.0005 and P=0.0002, respectively). PCA revealed clustering of the groups; PLS-DA modeling was able to distinguish the cohorts. These results were independent of medication and diet and were reproducible in the longitudinal cohort.

CONCLUSIONS: Specific urinary metabolites related to gut microbial metabolism differ between CD patients, UC patients, and controls. The emerging technique of urinary metabolic profiling with multivariate analysis was able to distinguish these cohorts.

Original language	English
Pages (from-to)	1435-1444
Number of pages	10
Journal	American Journal of Gastroenterology
Volume	104
Issue number	6
DOIs	https://doi.org/10.1038/ajg.2009.175
Publication status	Published - 2009

Keywords

Magnetic resonance spectroscopy
NMR-based metabonomics
Crohns disease
Ulcerative colitis
Intestinal microflora
Mucosa
Bacteria
Rats
Pathogenesis
Microbiota

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10.1038/ajg.2009.175

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Williams, H. R. T., Cox, I. J., Walker, D. G., North, B. V., Patel, V. M., Marshall, S. E., Jewell, D. P., Ghosh, S., Thomas, H. J. W., Teare, J. P., Jakobovits, S., Zeki, S., Welsh, K. I., Taylor-Robinson, S. D., & Orchard, T. R. (2009). Characterization of inflammatory bowel disease with urinary metabolic profiling. American Journal of Gastroenterology, 104(6), 1435-1444. https://doi.org/10.1038/ajg.2009.175

@article{db83dc1358b34828940db1337a8f4fc0,

title = "Characterization of inflammatory bowel disease with urinary metabolic profiling",

abstract = "OBJECTIVES: Distinguishing between the inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) is important for both management and prognostic reasons. Discrimination using noninvasive techniques could be an adjunct to conventional diagnostics. Differences have been shown between the intestinal microbiota of CD and UC patients and controls; the gut bacteria influence specific urinary metabolites that are quantifiable using proton highresolution nuclear magnetic resonance (NMR) spectroscopy. This study tested the hypothesis that such metabolites differ between IBD and control cohorts, and that using multivariate pattern-recognition analysis, the cohorts could be distinguished by urine NMR spectroscopy.METHODS: NMR spectra were acquired from urine samples of 206 Caucasian subjects (86 CD patients, 60 UC patients, and 60 healthy controls). Longitudinal samples were collected from 75 individuals. NMR resonances specific for metabolites influenced by the gut microbes were studied, including hippurate, formate, and 4-cresol sulfate. Multivariate analysis of all urinary metabolites involved principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA).RESULTS: Hippurate levels were lowest in CD patients and differed significantly between the three cohorts (P<0.0001). Formate levels were higher and 4-cresol sulfate levels lower in CD patients than in UC patients or controls (P=0.0005 and P=0.0002, respectively). PCA revealed clustering of the groups; PLS-DA modeling was able to distinguish the cohorts. These results were independent of medication and diet and were reproducible in the longitudinal cohort.CONCLUSIONS: Specific urinary metabolites related to gut microbial metabolism differ between CD patients, UC patients, and controls. The emerging technique of urinary metabolic profiling with multivariate analysis was able to distinguish these cohorts.",

keywords = "Magnetic resonance spectroscopy, NMR-based metabonomics, Crohns disease, Ulcerative colitis, Intestinal microflora, Mucosa, Bacteria, Rats, Pathogenesis, Microbiota",

author = "Williams, {Horace R. T.} and Cox, {I. Jane} and Walker, {David G.} and North, {Bernard V.} and Patel, {Venisha M.} and Marshall, {Sara E.} and Jewell, {Derek P.} and Subrata Ghosh and Thomas, {Huw J. W.} and Teare, {Julian P.} and Simon Jakobovits and Sebastian Zeki and Welsh, {Kenneth I.} and Taylor-Robinson, {Simon D.} and Orchard, {Timothy R.}",

year = "2009",

doi = "10.1038/ajg.2009.175",

language = "English",

volume = "104",

pages = "1435--1444",

journal = "American Journal of Gastroenterology",

issn = "0002-9270",

publisher = "Wolters Kluwer Health",

number = "6",

}

Williams, HRT, Cox, IJ, Walker, DG, North, BV, Patel, VM, Marshall, SE, Jewell, DP, Ghosh, S, Thomas, HJW, Teare, JP, Jakobovits, S, Zeki, S, Welsh, KI, Taylor-Robinson, SD & Orchard, TR 2009, 'Characterization of inflammatory bowel disease with urinary metabolic profiling', American Journal of Gastroenterology, vol. 104, no. 6, pp. 1435-1444. https://doi.org/10.1038/ajg.2009.175

TY - JOUR

T1 - Characterization of inflammatory bowel disease with urinary metabolic profiling

AU - Williams, Horace R. T.

AU - Cox, I. Jane

AU - Walker, David G.

AU - North, Bernard V.

AU - Patel, Venisha M.

AU - Marshall, Sara E.

AU - Jewell, Derek P.

AU - Ghosh, Subrata

AU - Thomas, Huw J. W.

AU - Teare, Julian P.

AU - Jakobovits, Simon

AU - Zeki, Sebastian

AU - Welsh, Kenneth I.

AU - Taylor-Robinson, Simon D.

AU - Orchard, Timothy R.

PY - 2009

Y1 - 2009

N2 - OBJECTIVES: Distinguishing between the inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) is important for both management and prognostic reasons. Discrimination using noninvasive techniques could be an adjunct to conventional diagnostics. Differences have been shown between the intestinal microbiota of CD and UC patients and controls; the gut bacteria influence specific urinary metabolites that are quantifiable using proton highresolution nuclear magnetic resonance (NMR) spectroscopy. This study tested the hypothesis that such metabolites differ between IBD and control cohorts, and that using multivariate pattern-recognition analysis, the cohorts could be distinguished by urine NMR spectroscopy.METHODS: NMR spectra were acquired from urine samples of 206 Caucasian subjects (86 CD patients, 60 UC patients, and 60 healthy controls). Longitudinal samples were collected from 75 individuals. NMR resonances specific for metabolites influenced by the gut microbes were studied, including hippurate, formate, and 4-cresol sulfate. Multivariate analysis of all urinary metabolites involved principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA).RESULTS: Hippurate levels were lowest in CD patients and differed significantly between the three cohorts (P<0.0001). Formate levels were higher and 4-cresol sulfate levels lower in CD patients than in UC patients or controls (P=0.0005 and P=0.0002, respectively). PCA revealed clustering of the groups; PLS-DA modeling was able to distinguish the cohorts. These results were independent of medication and diet and were reproducible in the longitudinal cohort.CONCLUSIONS: Specific urinary metabolites related to gut microbial metabolism differ between CD patients, UC patients, and controls. The emerging technique of urinary metabolic profiling with multivariate analysis was able to distinguish these cohorts.

AB - OBJECTIVES: Distinguishing between the inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) is important for both management and prognostic reasons. Discrimination using noninvasive techniques could be an adjunct to conventional diagnostics. Differences have been shown between the intestinal microbiota of CD and UC patients and controls; the gut bacteria influence specific urinary metabolites that are quantifiable using proton highresolution nuclear magnetic resonance (NMR) spectroscopy. This study tested the hypothesis that such metabolites differ between IBD and control cohorts, and that using multivariate pattern-recognition analysis, the cohorts could be distinguished by urine NMR spectroscopy.METHODS: NMR spectra were acquired from urine samples of 206 Caucasian subjects (86 CD patients, 60 UC patients, and 60 healthy controls). Longitudinal samples were collected from 75 individuals. NMR resonances specific for metabolites influenced by the gut microbes were studied, including hippurate, formate, and 4-cresol sulfate. Multivariate analysis of all urinary metabolites involved principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA).RESULTS: Hippurate levels were lowest in CD patients and differed significantly between the three cohorts (P<0.0001). Formate levels were higher and 4-cresol sulfate levels lower in CD patients than in UC patients or controls (P=0.0005 and P=0.0002, respectively). PCA revealed clustering of the groups; PLS-DA modeling was able to distinguish the cohorts. These results were independent of medication and diet and were reproducible in the longitudinal cohort.CONCLUSIONS: Specific urinary metabolites related to gut microbial metabolism differ between CD patients, UC patients, and controls. The emerging technique of urinary metabolic profiling with multivariate analysis was able to distinguish these cohorts.

KW - Magnetic resonance spectroscopy

KW - NMR-based metabonomics

KW - Crohns disease

KW - Ulcerative colitis

KW - Intestinal microflora

KW - Mucosa

KW - Bacteria

KW - Rats

KW - Pathogenesis

KW - Microbiota

U2 - 10.1038/ajg.2009.175

DO - 10.1038/ajg.2009.175

M3 - Article

C2 - 19491857

SN - 0002-9270

VL - 104

SP - 1435

EP - 1444

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

IS - 6

ER -

Characterization of inflammatory bowel disease with urinary metabolic profiling

Abstract

Keywords

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