Dataset Information

The fecal microbiota as a biomarker for disease activity in Crohn's disease.

ABSTRACT: Monitoring mucosal inflammation is crucial to prevent complications and disease progression in Crohn's disease (CD). Endoscopy is the current standard, but is invasive. Clinical activity scores and non-invasive biochemical markers do not correlate well with mucosal inflammation. Microbial perturbations have been associated with disease activity in CD. Therefore, we aimed to investigate its potential use to differentiate CD patients in remission from those with an exacerbation. From 71 CD patients repeated fecal samples were collected, resulting in 97 active disease and 97 remission samples based on a combination of biochemical and clinical parameters. The microbiota composition was assessed by pyrosequencing of the 16S rRNA V1-V3 region. Random Forest analysis was used to find the most discriminatory panel of operational taxonomic units (OTUs) between active and remission samples. An independent internal validation set was used to validate the model. A combination of 50 OTUs was able to correctly predict 73% of remission and 79% of active samples with an AUC of 0.82 (sensitivity: 0.79, specificity: 0.73). This study demonstrates that fecal microbial profiles can be used to differentiate between active and remission CD and underline the potential of the fecal microbiota as a non-invasive tool to monitor disease activity in CD.

SUBMITTER: Tedjo DI

PROVIDER: S-EPMC5062155 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The fecal microbiota as a biomarker for disease activity in Crohn's disease.

Tedjo Danyta I DI Smolinska Agnieszka A Savelkoul Paul H PH Masclee Ad A AA van Schooten Frederik J FJ Pierik Marieke J MJ Penders John J Jonkers Daisy M A E DM

Scientific reports 20161013

Monitoring mucosal inflammation is crucial to prevent complications and disease progression in Crohn's disease (CD). Endoscopy is the current standard, but is invasive. Clinical activity scores and non-invasive biochemical markers do not correlate well with mucosal inflammation. Microbial perturbations have been associated with disease activity in CD. Therefore, we aimed to investigate its potential use to differentiate CD patients in remission from those with an exacerbation. From 71 CD patient ...[more]

PMID: 27734914

Similar Datasets

Project description:Background:The treatment goal of Crohn's disease (CD) has moved towards achieving mucosal healing, resolution of transmural inflammation, and normalization of biomarkers. The purpose of this study was to evaluate how well computed tomography enterography (CTE) and fecal calprotectin (FC) correlated with endoscopic activity in newly diagnosed patients with CD and after 1 year of therapy. Methods:Consecutive patients with newly diagnosed CD were evaluated by endoscopy, CTE, and FC at diagnosis and 12 months after beginning immunosuppression. Endoscopic severity was assessed using the Simplified Endoscopic Score for Crohn's Disease (SES-CD). Biomarkers, clinical indexes, and FC were recorded on the day of ileocolonoscopy at diagnosis and 1 year after diagnosis. We adapted a CTE score for disease activity based on radiological signs of inflammation (i.e. mural thickness, mural hyperenhancement, mesenteric fat proliferation, mesenteric fat densification, comb sign, presence of strictures, fistulas, abscesses, ascites, and lymphadenopathy). Correlations between endoscopy, CTE, and FC were assessed using Spearman's rank correlation. Results:A total of 29 patients (48% women; median age 30 (24.5-35.5) years) were included in this prospective cohort. CTE findings significantly correlated with endoscopic findings. Endoscopic remission (ER) at 1-year follow up significantly correlated with improvement in mural hyperenhancement (p = 0.004), mesenteric fat densification (p = 0.001), comb sign (p = 0.004), and strictures (p = 0.008) in CTE. None of the CTE findings improved in patients without ER. FC correlated with SES-CD (rs = 0.696, p < 0.001) and with CTE features of inflammation (rs = 0.596, p < 0.001). A cut-off of 100 µg/g predicted ER with 92% sensitivity, 65% specificity, and 83% accuracy (area under curve 0.878, p < 0.001). Conclusions:CTE findings and FC levels correlated with endoscopic activity in CD both at diagnosis and at 1-year follow up. These two noninvasive markers of disease activity may be used as an alternative to endoscopy to monitor disease response to therapy.

Project description:The fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive of numerous disease states. Less well studied is the effect of immunomodulatory therapy on the microbiota and its role in response to therapy. This study explored associations between the fecal microbiota and therapeutic response of Crohn's disease (CD) patients treated with ustekinumab (UST; Stelara) in the phase 2 CERTIFI study. Using stool samples collected over the course of 22 weeks, the composition of these subjects' fecal bacterial communities was characterized by sequencing the 16S rRNA gene. Subjects in remission could be distinguished from those with active disease 6 weeks after treatment using random forest models trained on subjects' baseline microbiota and clinical data (area under the curve [AUC] of 0.844, specificity of 0.831, sensitivity of 0.774). The most predictive operational taxonomic units (OTUs) that were ubiquitous among subjects were affiliated with Faecalibacterium and Escherichia or Shigella The median baseline community diversity in subjects in remission 6 weeks after treatment was 1.7 times higher than that in treated subjects with active disease (P = 0.020). Their baseline community structures were also significantly different (P = 0.017). Two OTUs affiliated with Faecalibacterium (P = 0.003) and Bacteroides (P = 0.022) were significantly more abundant at baseline in subjects who were in remission 6 weeks after treatment than those with active CD. The microbiota diversity of UST-treated clinical responders increased over the 22 weeks of the study, in contrast to nonresponsive subjects (P = 0.012). The observed baseline differences in fecal microbiota and changes due to therapeutic response support the potential for the microbiota as a response biomarker.IMPORTANCE CD is a global health concern, with increasing incidence and prevalence, causing large economic and health care impacts. Finding prognostic biomarkers that give clinicians the ability to identify patients more likely to respond to CD treatment at diagnosis will reduce the time subjects receive drugs that are unlikely to be beneficial. OTUs associated with remission after treatment induction, especially Faecalibacterium, could be biomarkers for successful UST treatment of anti-tumor necrosis factor alpha (anti-TNF-α) refractory CD patients. More broadly, these results suggest that the fecal microbiota could be a useful noninvasive biomarker for directing or monitoring the treatment of gastrointestinal diseases.

Project description:Background and Aims: Anti-tumor necrosis factor mAb (i.e., adalimumab, ADA) is currently used in the treatment of patients with Crohn's disease (CD). However, its regulation on fecal microbiota is still not fully understood. Methods: A retrospective analysis was conducted on 115 patients with CD who received treatment with ADA for 12 weeks at the Inflammatory Bowel Disease Center in Shanghai Tenth People's Hospital and Department of Gastroenterology in Shanghai General Hospital. The Crohn's disease activity index (CDAI) evaluation was applied to patients before ADA therapy at week 0, 4, 8, and 12. Clinical remission (CR) was defined as the CDAI < 150. All patients underwent ileocolonoscopy or enteroscopy at baseline (week 0) and week 12. Crohn's Disease Endoscopic Index of Severity (CDEIS) scores were calculated by two experienced physicians to assess endoscopic activity. Mucosal healing (MH) was assigned a CDEIS score between 0 and 3. Fecal samples were collected from eight CD patients at baseline and week 12, and the microbiota was analyzed by using 16S RNA sequencing. Results: At week 12, CR was achieved in 70.6% (72/102) of the patients with active CD. A total of 47.1% (48/102) of the patients with active CD attained MH, among which, 56.6% (30/53) of the patients with mildly active CD (3 ≤ CDEIS <9) and 48.0% (12/25) of the moderately active CD patients (9 ≤ CDEIS <12) attained MH, but only 25.0% (6/24) achieved MH in severely active CD patients (CDEIS ≥12). The efficacy of ADA was not associated with lesion locations (χ 2 = 0.409, p = 0.815). Unexpectedly, we found an increase in protective microbiota at the genus level (e.g., Barnesiella, Anaerostipes, Tyzzerella, Lachnoclostridium, and Lachnospiraceae_unclassified) but a decrease in pathogenic bacteria (Escherichia-Shigella) in fecal samples of the ADA-responsive group (ADA-R) when compared with those in the ADA-nonresponsive group (ADA-NR). Notably, the gene bglX coding β-glucosidase and gph encoding phosphoglycolate phosphatase were enriched in fecal samples of ADA-R. Conversely, the abundance of genes coding ATP-binding cassette (ABC) transporter system proteins was significantly enriched in fecal samples of ADA-NR when compared with that of the ADA-R. Conclusion: This study reveals that ADA markedly improves clinical remission and induces MH in mildly to moderately active CD patients and that distinct changes in the gut microbiota can be used to predict the efficacy of ADA.

Dataset Information

The fecal microbiota as a biomarker for disease activity in Crohn's disease.

Publications

The fecal microbiota as a biomarker for disease activity in Crohn's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets