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Objective: A decade of microbiome studies has linked IBD to an alteration in the gut microbial community of genetically predisposed subjects. However, existing profiles of gut microbiome dysbiosis in adult IBD patients are inconsistent among published studies, and did not allow the identification of microbial signatures for CD and UC. Here, we aimed to compare the faecal microbiome of CD with patients having UC and with non-IBD subjects in a longitudinal study., Design: We analysed a cohort of 2045 non-IBD and IBD faecal samples from four countries (Spain, Belgium, the UK and Germany), applied a 16S rRNA sequencing approach and analysed a total dataset of 115 million sequences., Results: In the Spanish cohort, dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Tested against the whole cohort, the signature achieved an overall sensitivity of 80% and a specificity of 94%, 94%, 89% and 91% for the detection of CD versus healthy controls, patients with anorexia, IBS and UC, respectively., Conclusions: Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Although incrimination of the intestinal microbiota in the pathogenesis of IBD is widely accepted, few data are available about the role of specific bacteria. Potentially, Faecalibacterium prausnitzii, bacteria with anti-inflammatory properties, might be deficient in ulcerative colitis (UC)., Aim: To quantify F. prausnitzii in the faecal microbiota of UC patients in remission and determine its relationship with relapse., Methods: A cross-sectional study included 116 UC patients in remission, 29 first-degree relatives and 31 healthy controls. A subset of eighteen patients, recruited during the first month of remission, underwent a 1-year follow-up. Total bacteria and F. prausnitzii were measured by quantitative Real Time PCR (qPCR, copies/g). Calprotectin was determined as inflammatory index (μg/g)., Results: We found that F. prausnitzii was reduced in patients (median, IQR: 1.4 × 10⁸ , 5.1 × 10⁷-4.5 × 10⁸) and relatives (1.7 × 10⁸, 9.3 × 10⁷-5.1 × 10⁸) vs. controls (6.5 × 10⁸, 3.7 × 10⁸-1.6 × 10⁹, P < 0.0001). Moreover, low counts of F. prausnitzii were associated with less than 12 months of remission (8.0 × 10⁷, 2.0 × 10⁷-3.5 × 10⁸ vs. 2.1 × 10⁸, 1.0 × 10⁸-7.9 × 10⁸, P < 0.001) and more than 1 relapse/year (8.0 × 10⁷, 3.2 × 10⁷-3.8 × 10⁸ vs. 1.9 × 10⁸, 6.8 × 10⁷-6.0 × 10⁸, P < 0.01). When patients were followed up, F. prausnitzii increased steadily until reaching similar levels to those of controls if remission persisted (2.9 × 10⁸, 9.3 × 10⁶-1.2 × 10⁹; calprotectin: 76, 19-212), whereas it remained low if patients relapsed (2.2 × 10⁸, 1.4 × 10⁶-3.3 × 10⁸; calprotectin: 1760, 844-3662 P < 0.05 vs. controls)., Conclusions: Defective gut colonisation by F. prausnitzii occurred in UC patients during remission and in their unaffected relatives. The recovery of the F. prausnitzii population after relapse is associated with maintenance of clinical remission., (© 2013 John Wiley & Sons Ltd.)

Background and Aim: Studies have identified abnormal characteristics of the gut microbiota in patients with active IBD, but whether the changes are causal or secondary to inflammation remains uncertain. We investigated dynamics of fecal microbiota in ulcerative colitis (UC) during remission by genomic technology., Patients and Methods: Patients in clinical remission and on stable maintenance mesalazine therapy were recruited (N = 33). Fecal samples were collected at regular intervals over a period of 1 yr. Sixteen patients who remained in remission and eight healthy controls were included in the analysis. Variable V6 to V8 regions of the 16S rRNA gene in DNA extracts from fecal samples were amplified by polymerase chain reaction. Amplicons were separated by denaturant gradient gel electrophoresis, band profiles were compared by software, and similarity indices were calculated from densitometric curves., Results: Band profiles showed unique patterns with low similarity index between individuals, suggesting host specificity in the predominant microbiota. Within the same individual, profiles were stable in controls but varied notably over time in patients. In controls, the similarity index was remarkably stable (78 +/- 8% mean +/- SD) over a period of 24 months. However, patients showed a steady decline in similarity index versus the initial profile, dropping down to 42 +/- 24% at month 3 of follow-up and to 23 +/- 19% at month 12 (P < 0.001). Biodiversity of the dominant microbiota, as estimated by number of bands, was lower in patients (17 +/- 4) than controls (23 +/- 4, P < 0.01)., Conclusion: Molecular analysis of fecal bacteria in patients with inactive UC shows low biodiversity and temporal instability.

Background: We have developed a technique for measuring fecal excretion of human DNA by assuming that luminal desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa. However, the clinical usefulness of this technique in the follow-up of patients with ulcerative colitis has not been established. The aim of this study was to determine the stability of fecal DNA in inactive ulcerative colitis and its potential value as an indicator of relapse., Methods: The 54 patients with clinically quiescent ulcerative colitis in this prospective study were followed for 12 months or until clinical relapse (clinical activity index > 7). Fecal calprotectin concentration was determined by ELISA, and fecal DNA concentration was determined by quantitative PCR., Results: During the year of follow-up, 23 of the 54 patients relapsed, with a median increase in the colitis activity index from 1.0 to 8.0 (P < 0.01). Median fecal DNA remained unchanged in patients with stable, inactive colitis, ranging from 6.8 copies/microg at inclusion to 1.7 copies/microg at the end of follow-up. Fecal calprotectin level also was unchanged, ranging from 414.0 microg/g at inclusion to 128.9 microg/g at the end of follow-up. In contrast, fecal DNA concentration increased significantly in patients who relapsed (259.0 versus 3.9 copies/microg at entry; P < 0.01). Similar increases in relapsing patients were also observed with fecal calprotectin. ROC curve analysis to assess the accuracy of fecal DNA and calprotectin in detecting relapses during follow-up yielded similar results., Conclusions: Fecal DNA concentration remained stable in patients with inactive ulcerative colitis but increased significantly with relapses. Determining fecal DNA concentration may be a new objective instrument to use in the follow-up of patients.

Background & Aims: Several indices evaluate disease activity in ulcerative colitis, but most have drawbacks to their application (invasiveness, complexity, or lack of specificity), and discrepancies between them are frequent. Assuming that desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa, we hypothesized that fecal excretion of human DNA is an index of mucosal inflammation and damage. The aim of our study was to determine whether excretion of human DNA is useful in the evaluation of disease activity in ulcerative colitis., Methods: Thirty-one controls and 36 ulcerative colitis patients were included. Ulcerative colitis patients and controls underwent colonoscopic examination after preparation by gut lavage with polyethylene-glycol electrolyte solution. In patients, disease activity was established using the clinical index of Rachmilewitz and an endoscopic score. Feces and gut lavage fluid were obtained and DNA levels were measured by quantitative polymerase chain reaction of the human beta-globin gene., Results: Fecal DNA excretion correlated with the clinical index (r = 0.59, P < 0.05) and the endoscopic score (r = 0.76, P < 0.01). Gut lavage fluid DNA levels also correlated with clinical and endoscopic activity scores (r = 0.41 and 0.51, respectively, P < 0.05). Fecal DNA excretion was significantly higher in patients with endoscopically or clinically active disease than in controls or patients in remission. Fecal DNA excretion discriminates between endoscopically active disease and remission (sensitivity 0.67, specificity 1.00, P < 0.01)., Conclusions: Excretion of human DNA in feces, as an expression of cellular desquamation, is a novel noninvasive technique to objectively assess disease activity in ulcerative colitis.