Metabonomics of inflamma tory bowel disease
UC patients had lower levels of shortchain fatty acids but elevated levels of amino acids. In addition, the presence of glycerol differentiated CD from UC patients. No metabonomic studies for IBD diagnosis or prognosis have been published, says Marchesi. In fact, he recently went to a meeting in which an attendee announced that such an investigation couldn’t be done. Marchesi stood up and responded that not only is such a study possible, but that he and his collaborators already had done it!
glycerol, but they are not usually found in the human gut,” he explains. “But at We’ve all had bouts of gastrointestinal the same time, we still don’t fully know (GI) irritation, but patients with inflamwhat lives in the human gut.” matory bowel disease (IBD) have more To dig deeper into the metabonomes, than a simple upset stomach. They have the researchers applied multivariate severe abdominal pain, diarrhea, and analysis techniques to the data. Prinvomiting. IBD is actually a collection cipal components analysis (PCA) is of inflammatory conditions, including an unsupervised and unbiased way Crohn’s disease (CD) and ulcerative of separating samples into groups. colitis (UC), which affect the GI tract. In With this approach, the IBD patients CD, inflammation can occur anywhere were distinguished from controls, but along the GI tract, but in UC, inflammaUC and CD patients were less clearly tion typically is confined to the colon. separated from each other. Next, the As many as 4 million people researchers used a method worldwide are affected, and called orthogonal projecthe incidence of IBD is growtion to latent structures ing, especially in developed discriminant analysis (O(a) 0.02 0.6 countries. Diagnosis typiPLS-DA) to specifically look -0.02 cally is invasive; an endofor candidate biomarkers. scope, or a small camera, is This analysis removes some -0.06 0 used to peer into the GI tract. of the noise caused by pa(b) 0.02 In addition, blood tests can rameters that are not related 0.6 determine whether inflamto the disease, such as age. 0 mation is present, but no With O-PLS-DA coefficient -0.02 0 biomarker exists yet for IBD plots, researchers can de(c) 0.04 or for distinguishing various termine which metabolites 0.6 IBD conditions. are elevated or decreased in 0 The causes of the disease samples from patients with are not well understood, but a particular disease. -0.02 0 4 3.5 3 2.5 2 1.5 1 a mix of genetic and enviThe levels of short-chain 1H -ppm � ronmental factors is likely fatty acids, such as acetate to blame. For example, the and butyrate, were reduced composition of the bacteria in IBD patients compared 1 What’s the difference? H-NMR metabonomics methods were used to in the gut (the microbiota) with controls. These mefind metabolites that distinguish (a) CD patients from controls, (b) UC pais known to be affected in tabolites were slightly more tients from controls, and (c) CD patients from UC patients. IBD patients. As Julian Marabundant in UC compared chesi at University College with CD patients. Marchesi Cork (UCC; Ireland) points out, “It’s “I think the researcher thought that says that butyrate is an interesting a chicken and egg situation. Did the the patterns would be too complex,” he compound because it is known as an disease happen and that changed the explains. He says that Holmes’s group, anti-inflammatory agent and as a main bacteria, or did the bacteria change and however, has the necessary expertise to energy source for intestinal cells. In that caused the disease?” Regardless, interpret the complicated fecal spectra. addition, amino acids were more abunMarchesi and his group realized that And according to Holmes, the effort is dant in IBD samples than in those from studying the metabolites produced by well worth it. “Metabonomics, especontrols. Holmes explains that this the microbiota could give them imporcially NMR-based metabonomics, is result suggests that IBD patients have tant clues about what was going on in very robust, reproducible, and you can difficulties absorbing nutrients. patients. So his group teamed up with get a rapid profile of a sample in 5 or 10 Now that this pilot study has conexperts in metabonomics to identify minutes,” she says. cluded, the researchers will expand metabolites that could be used as bioIn the study, fecal samples from the project to include samples from pamarkers of IBD. CD, UC, and healthy controls were tients with diverse ethnic backgrounds. In this issue of JPR (pp 546–551), analyzed by 1H NMR. The researchers In addition, samples from patients with Marchesi, Elaine Holmes, Yulan Wang, got a general impression of some difother GI conditions will be compared and colleagues at UCC, Imperial Colferences just by looking at the spectra. with the IBD samples to determine lege London, Nestlé Research Center For example, low levels of butyrate and specificity. Holmes says that the re(Switzerland), and AstraZeneca (U.K.) high levels of glycerol were observed in searchers also will continue to develop report a noninvasive metabonomic CD samples compared with those from the methodology and will use MS and 1H-NMR techniques to analyze samples analysis of fecal samples from IBD paUC patients and controls. Marchesi tients and healthy controls. They found says that the glycerol result was odd. obtained over time. that, compared with controls, CD and “There are some bacteria that can make —Katie Cottingham
Journal of Proteome Research • Vol. 6, No. 2, 2007 439
