Rapid and noninvasive metabonomic characterization of inflammatory bowel disease

被引:473
作者
Marchesi, Julian R.
Holmes, Elaine
Khan, Fatima
Kochhar, Sunil
Scanlan, Pauline
Shanahan, Fergus
Wilson, Ian D.
Wang, Yulan
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Biomol Med, SORA Div, Fac Med, London SW7 2AZ, England
[2] Natl Univ Ireland Univ Coll Cork, Dept Microbiol, Cork, Ireland
[3] Natl Univ Ireland Univ Coll Cork, Alimentary Pharmabiot Ctr, Cork, Ireland
[4] Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland
[5] AstraZeneca, Dept Drug Metab & Pharmacokinet, Macclesfield SK10 4TG, Cheshire, England
关键词
Crohn's disease; ulcerative colitis; metabonomics; feces; NMR spectroscopy;
D O I
10.1021/pr060470d
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) have a major impact on the health of individuals and populations. Accurate diagnosis of inflammatory bowel disease (IBD) at an early stage, and correct differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is important for optimum treatment and prognosis. We present here the first characterization of fecal extracts obtained from patients with CD and UC by employing a noninvasive metabonomics approach, which combines high resolution H-1 NMR spectroscopy and multivariate pattern recognition techniques. The fecal extracts of both CD and UC patients were characterized by reduced levels of butyrate, acetate, methylamine, and trimethylamine in comparison with a control population, suggesting changes in the gut microbial community. Also, elevated quantities of amino acids were present in the feces from both disease groups, implying malabsorption caused by the inflammatory disease or an element of protein losing enteropathy. Metabolic differences in fecal profiles were more marked in the CD group in comparison with the control group, indicating that the inflammation caused by CD is more extensive in comparison with UC and involves the whole intestine. Furthermore, glycerol resonances were a dominant feature of fecal spectra from patients with CD but were present in much lower intensity in the control and UC groups. This work illustrates the potential of metabonomics to generate novel noninvasive diagnostics for gastrointestinal diseases and may further our understanding of disease mechanisms.
引用
收藏
页码:546 / 551
页数:6
相关论文
共 44 条
[1]   MLEV-17-BASED TWO-DIMENSIONAL HOMONUCLEAR MAGNETIZATION TRANSFER SPECTROSCOPY [J].
BAX, A ;
DAVIS, DG .
JOURNAL OF MAGNETIC RESONANCE, 1985, 65 (02) :355-360
[2]   The genetics of inflammatory bowel disease [J].
Bonen, DK ;
Cho, JH .
GASTROENTEROLOGY, 2003, 124 (02) :521-536
[3]  
Brindle JT, 2002, NAT MED, V8, P1439, DOI 10.1038/nm802
[4]   Statistical total correlation spectroscopy:: An exploratory approach for latent biomarker identification from metabolic 1H NMR data sets [J].
Cloarec, O ;
Dumas, ME ;
Craig, A ;
Barton, RH ;
Trygg, J ;
Hudson, J ;
Blancher, C ;
Gauguier, D ;
Lindon, JC ;
Holmes, E ;
Nicholson, J .
ANALYTICAL CHEMISTRY, 2005, 77 (05) :1282-1289
[5]   Evaluation of the orthogonal projection on latent structure model limitations caused by chemical shift variability and improved visualization of biomarker changes in 1H NMR spectroscopic metabonomic studies [J].
Cloarec, O ;
Dumas, ME ;
Trygg, J ;
Craig, A ;
Barton, RH ;
Lindon, JC ;
Nicholson, JK ;
Holmes, E .
ANALYTICAL CHEMISTRY, 2005, 77 (02) :517-526
[6]   The epidemiology of paediatric inflammatory bowel disease [J].
Cosgrove, M ;
AlAtia, RF ;
Jenkins, HR .
ARCHIVES OF DISEASE IN CHILDHOOD, 1996, 74 (05) :460-461
[7]   Comparative study of normal and osteoarthritic canine synovial fluid using 500 MHz 1H magnetic resonance spectroscopy [J].
Damyanovich, AZ ;
Staples, JR ;
Chan, ADM ;
Marshall, KW .
JOURNAL OF ORTHOPAEDIC RESEARCH, 1999, 17 (02) :223-231
[8]   T cell specificity and cross reactivity towards enterobacteria, Bacteroides, Bifidobacterium, and antigens from resident intestinal flora in humans [J].
Duchmann, R ;
May, E ;
Heike, M ;
Knolle, P ;
Neurath, M ;
zum Büschenfelde, KHM .
GUT, 1999, 44 (06) :812-818
[9]   HIGH-RESOLUTION PROTON MAGNETIC-RESONANCE SPECTROSCOPY OF CYST FLUIDS FROM PATIENTS WITH POLYCYSTIC KIDNEY-DISEASE [J].
FOXALL, PJD ;
PRICE, RG ;
JONES, JK ;
NEILD, GH ;
THOMPSON, FD ;
NICHOLSON, JK .
BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1138 (04) :305-314
[10]   Genotypes and phenotypes in Crohn's disease: do they help in clinical management? [J].
Gasche, C ;
Grundtner, P .
GUT, 2005, 54 (01) :162-167