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Serologic biomarkers for inflammatory bowel disease (IBD) have yielded variable differentiating ability. Quantitative analysis of a large number of metabolites is a promising method to detect IBD biomarkers. Human subjects with active Crohn’s disease (CD) and active ulcerative colitis (UC) were identified, and serum, plasma, and urine specimens were obtained.

We characterized 44 serum, 37 plasma, and 71 urine metabolites by use of 1H NMR spectroscopy and “targeted analysis” to differentiate between diseased and non-diseased individuals, as well as between the CD and UC cohorts. We used multiblock principal component analysis and hierarchical OPLS-DA for comparing several blocks derived from the same “objects” (e.g., subject) to examine differences in metabolites. In serum and plasma of IBD patients, methanol, mannose, formate, 3-methyl-2-oxovalerate, and amino acids such as isoleucine were the metabolites most prominently increased, whereas in urine, maximal increases were observed for mannitol, allantoin, xylose, and carnitine. Both serum and plasma of UC and CD patients showed significant decreases in urea and citrate, whereas in urine, decreases were observed, among others, for betaine and hippurate. Quantitative metabolomic profiling of serum, plasma, and urine discriminates between healthy and IBD subjects.

However, our results show that the metabolic differences between the CD and UC cohorts are less pronounced. Crohn’s disease (CD) and ulcerative colitis (UC), the two major subtypes of chronic inflammatory bowel disease (IBD), cause significant morbidity in affected individuals.

The prevalence ranges from 37 to 249 cases per 100,000 people for UC and from 26 to 319 cases per 100,000 people for CD in the North American population, with similar incidences in other developed countries. While the pathophysiology of IBD is not fully understood, it has been widely accepted that multiple components, including genetic, environmental, and microbiological factors, contribute to the occurrence and perpetuation of the disease. Current therapeutic options consist of anti-inflammatory medications as well as corticosteroids and immunosuppressive and novel biological agents. However, some individuals fail to respond to these therapies, and these agents are associated with significant side effects. In addition, CD and UC, while sharing several similar pathologic and clinical features, do have distinct differences in prognosis and management.

Therefore, to minimize side effects in IBD therapy, appropriate therapeutic decision-making through accurate diagnosis and regular surveillance is crucial. Currently, diagnosis relies upon clinical, endoscopic, histologic, and radiologic techniques that can be time-consuming and costly. Endoscopy is a technique with risks, including a 1 in 1000 risk of bowel perforation. Furthermore, differentiating between the two subtypes of disease endoscopically and even histologically may be challenging in certain situations. Less invasive methods for diagnosis, such as determination of biomarkers from urine, serum, or feces, however, would be of significant advantage and useful for primary diagnosis, surveillance, and early detection of relapses. Additionally, non-invasive biomarkers could be used by gastroenterologists to triage referral for patients with symptoms such as abdominal pain and diarrhea.

Several investigators have addressed this issue by performing non-targeted analysis of metabolites in animal models of colitis using mass spectroscopy as well as 1H NMR spectroscopy. The latter method has also been applied to IBD patients to characterize metabolites in urine, fecal extracts, and biopsy samples. A recent study employing ion cyclotron resonance-Fourier transform mass spectrometry to discriminate between 1000 metabolites revealed differences in fecal samples collected from identical twin pairs, including healthy individuals and CD patients. Another study clearly distinguished between IBD patients and healthy individuals by use of multivariate indexes established from plasma aminograms. Analysis of metabolites is therefore rapidly emerging as a powerful method for characterizing IBD in experimental animal models and humans. Though various markers or marker panels have been tested in clinical trials, there is no ideal marker that is able to diagnose or predict IBD. Most useful markers in clinical practice include acute phase proteins such as C-reactive protein, the fecal markers calprotectin and lactoferrin, and serologic markers such as the DNase-sensitive antineutrophil cytoplasmic antibody p-ANCA that is present in sera of 60% of UC and 20% of CD patients. Farming simulator 2011 platinum edition cracked. Non alphanumeric character s.