Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn’s disease and healthy individuals

Abstract

This study employs spectroscopy-based metabolic profiling of fecal extracts from healthy subjects and patients with active or inactive ulcerative colitis (UC) and Crohn's disease (CD) to substantiate the potential use of spectroscopy as a non-invasive diagnostic tool and to characterize the fecal metabolome in inflammatory bowel disease (IBD). Stool samples from 113 individuals (UC 48, CD 44, controls 21) were analyzed by 1 H nuclear magnetic resonance (NMR) spectroscopy (Bruker 600 MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with principal component analysis and orthogonal-projection to latent structure-discriminant analysis using SIMCA-P ? 12 and MATLAB. Significant differences were found in the metabolic profiles making it possible to differentiate between active IBD and controls and between UC and CD. The metabolites holding differential power primarily belonged to a range of amino acids, microbiota-related short chain fatty acids, and lactate suggestive of an inflammation-driven malabsorption and dysbiosis of the normal bacterial ecology. However, removal of patients with intestinal surgery and anti-TNF-a antibody treatment eliminated the discriminative power regarding UC versus CD. This study consequently demonstrates that 1 H NMR spectroscopy of fecal extracts is a potential non-invasive diagnostic tool and able to characterize the inflammationdriven changes in the metabolic profiles related to malabsorption and dysbiosis. Intestinal surgery and medication are to be accounted for in future studies, as it seems to be factors of importance in the discriminative process.

Metabolomics in the Clinical Diagnosis of Inflammatory Bowel Disease

“…Marchesi et al [32] demonstrated that the relative amounts of amino acids and glycerol were increased and the levels of butyrate and acetate were decreased in the feces of CD patients which contributed to the differentiation between patients with CD and UC. In a recent study of Bjerrum et al [33] , a clear different differentiation between CD and UC patients based on fecal profiles was found. However, after removal of patients with intestinal surgery and anti-TNF-α treatment, the distinction was eliminated indicating the necessity to evaluate the results for possible confounding factors.…”

“…As a result of the dysbiosis identified in fecal samples of IBD patients, a number of studies investigated the metabolite profile in feces or fecal extracts. In the studies by Marchesi et al [32] and Bjerrum et al [33] , higher levels of amino acids and but lower levels of SCFA were found in fecal extracts of IBD patients as compared to HCs using the 1 H-NMR technology. The depletion of SCFA in IBD patients versus HCs are not novel and have often been described in the past few years.…”

Sample preparation optimization in fecal metabolic profiling

“…Metabolomic analysis of fecal samples has revealed calprotectin or lactoferrin as valuable biomarkers for early detection of inflammatory bowel diseases [24,25]. NMR spectroscopy [26][27][28][29], GC-MS [30][31][32] and LC-MS [33][34][35] have been used to find biomarkers of intestinal diseases in stool material from human and rodents. The use of metabolomics in the study of bowel diseases was recently reviewed [23,36].…”

Duration of Inflammatory Bowel Disease Is Associated With Increased Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis and IBD

“…The pathobiological mechanisms underlying our findings remain unclear but may be related to the altered bile acid milieu or altered microbiome (17,18) and metabolome (19–21) that exist in a chronically inflamed colon and can persist after colectomy. Altered bile acid profiles in the setting of chronic IBD and after colectomy have been reported (22–24), and whether these changes could injure the biliary epithelia via the enterohepatic circulation or modify the biliary microenvironment to promote malignant transformation remains plausible, although unconfirmed.…”