Metabolomics as a diagnostic tool in gastroenterology

Table 1 Overview of web-based databases for metabolite identification

Database	URL or web address	Extra information
Human Metabolome Database (HMDB)	http://www.hmdb.ca/	Wishart et al[34]
Madison Metabolomics Consortium (MMC) Database	http://mmcd.nmrfam.wisc.edu/	Cui et al[35]
Biological Magnetic Resonance Data Bank (BMRB)	http://www.bmrb.wisc.edu/	Ulrich et al[36]
Golm Metabolome Database	http://csbdb.mpimp-golm.mpg.de/csbdb/gmd/gmd.html	Kopka et al[37]
BiGG (a knowledgebase of Biochemically, Genetically and Genomically structured genome-scale metabolic network reconstructions)	http://bigg.ucsd.edu/	Schellenberger et al[38]
SetupX and BinBase	http://fiehnlab.ucdavis.edu/	Skogerson et al[39]
MassBank	http://www.massbank.jp/	Horai et al[40]
METLIN	http://metlin.scripps.edu/	Smith et al[41]

Table 2 Overview of the studies that applied metabolomics to discriminate inflammatory bowel diseases and/or irritable bowel syndrome patients from controls

Reference	Analytical platform	Biofluid	Samples	Observations
Marchesi et al[47]	1HNMR	Faecal extracts	CD (n = 10), UC (n = 10), HC (n = 13)	Depletion of SCFA and methylamine and trimethylamine in CD patients Higher amounts of amino acids in UC and CD compared to healthy controls
Jansson et al[64]	ICR-FT/MS	Faecal water	10 twin pairs with CD, 7 healthy twin pairs	Discrimination based on disease location (ileal or colonic CD) significant differences in the types and number of metabolites within specific pathways, including tyrosine and phenyl-alanine metabolism and bile acid and fatty acid biosynthesis
Le Gall et al[49]	1HNMR	Faecal water	UC (n = 13; 31 samples), IBS (n = 10; 21 samples), HC (n = 22; 72 samples)	Discrimination between UC and HC; no classification of IBS Increased taurine and cadaverine in UC
Walton et al[50]	GC-MS	Faeces	UC (n = 20), CD (n = 22), IBS (n = 26), HC (n = 19)	Increased concentrations of ester and alcohol derivates of short-chain fatty acids and indole in CD After treatment, metabolite patterns are more similar to those of HC
Williams et al[52]	1HNMR	Urine	CD (n = 86), UC (n = 60), HC (n = 60)	Discrimination between CD, UC and HC Significantly different metabolites include hippurate, p-cresol sulfate and formate Clustering independent of diet and medication
Schicho et al[53]	1HNMR	Urine, serum, plasma	CD (n = 20), UC (n = 20), HC (n = 40)	IBD patients could be discriminated from HC, differences between CD and UC less pronounced Discriminating metabolites include amino acids, creatine, creatinine, metabolites of urea cycle, monosaccharides, hippurate (urine)
Stephens et al[54]	1HNMR	Urine	CD (n = 30), UC (n = 30), HC (n = 60)	Metabolites for distinguishing IBD from HC: TCA cycle intermediates, amino acids metabolites derived from gut microflora (methanol, formate, hippurate, acetate, and methylamine); as well as the other metabolites trigonelline, creatine, urea, and taurine No discrimination between UC and CD after removal of patients with surgical intervention confounder
Ooi et al[58]	GC-MS	Colonic biopsies, serum	Colonic biopsies: UC (n = 22), serum: UC (n = 13), CD (n = 21), HC (n = 17)	Reduced levels of amino acids resulting in reduced levels of TCA cycle related downstream molecules in colonic tissue of UC Serum amino acid profiling enabled discrimination between UC and CD
Bjerrum et al[60]	1HNMR	Colonic biopsies, colonocytes, lymphocytes, urine	Active UC (n = 35), quiescent UC (n = 33), HC (n = 25)	No discrimination between active UC, inactive UC and HC based on urine or lymphocyte profiles Inactive UC could not be differentiated from HC Active UC characterized by higher antioxidants and amino acids and lower levels of lipid, myo-inositol, betaine and glycerophosphoglycine 20% of inactive UC had similar profile as active UC
Bezabeh et al[63]	1HNMR	Colonic biopsies	UC (n = 26; 45 samples), CD (n = 21; 31 samples), controls (38 non-inflamed IBD, 25 cancer patients)	Accurate classification of UC vs CD Some non-inflamed tissues from IBD had abnormal NMR-spectra
Balasubramanian et al[61]	1HNMR	Colonic biopsies	Active UC (n = 20), Inactive UC (n = 11), Active CD (n = 20), Inactive CD (n = 6), HC (n = 26)	Higher α-glucose and lower amino acids, membrane components, lactate and succinate in active UC and CD compared to HC Lower lactate, glycerophosphorylcholine and myo-inositol in inactive UC and lower lactate in inactive CD compared to HC Lower formate in active UC vs active CD
Sharma et al[62]	1HNMR	Colonic biopsies (inflamed and non-inflamed)	UC (n = 12), CD (n = 9), controls (n = 25)	No differentiation between inflamed and non-inflamed samples Lower levels of amino acids, membrane components, lactate and formate in IBD vs controls and higher levels of glucose
Hisamatsu et al[66]	AA analyzer	plasma	CD (n = 165), UC (n = 222), HC (n = 210)	Multivariate indexes established from plasma aminograms distinguish CD or UC from HC Other indexes distinguish active UC and CD from each remission patients and correlate with disease activity indices
Zhang et al[67]	1HNMR	Serum	Active UC (n = 20), HC (n = 19)	Active UC displayed increased 3-hydroxybutyrate, β-glucose, α-glucose and phenylalanine and decreased lipid compared to healthy controls
Ponnusamy et al[71]	GC-MS	Faeces	IBS (n = 11) vs non-IBS (n = 8)	Elevated levels of amino acids and phenolic compounds that were highly correlated with abundance of lactobacilli and Clostridium
Ohman et al[69]	GC-MS	Faeces	IBS-D (n = 30), CD (n = 62), UC (n = 48), HC (n = 109)	Significantly more esters in IBS-D, association of aldehydes with IBD Accurate separation of IBS-D from active CD, UC and HC

SCFA: Short-chain fatty acids; IBD: Inflammatory bowel diseases; IBS: Irritable bowel syndrome; TCA: Tricarboxylic acid; HNMR: Nuclear magnetic resonance; ICR-FT/MS: Fourier transform ion cyclotron resonance mass spectrometry; GC-MS: Gas chromatography-mass spectrometry.