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. 2017 May;66(5):813-822.
doi: 10.1136/gutjnl-2016-313235. Epub 2017 Feb 7.

A microbial signature for Crohn's disease

Affiliations

A microbial signature for Crohn's disease

Victoria Pascal et al. Gut. 2017 May.

Abstract

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.

Keywords: INFLAMMATORY BOWEL DISEASE; INTESTINAL BACTERIA.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Microbiome stability. Unweighted UniFrac distances were calculated between different time periods for healthy relatives HR(CD) (relatives of patients with CD), HR(UC) (relatives of patients with UC), and patients with CD and UC (3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months). CD-RC and UC-RC refer to samples collected during recurrence onset. At 3-month interval, patients with CD and UC presented significant differences in their UniFrac indexes compared with their HR (Mann-Whitney U test, *p=0.01). We compared the UniFrac indexes obtained between samples collected at baseline and the rest of the time points using the mixed-design ANOVA model and found that the microbiome of patients with CD was significantly more unstable than that of patients with UC (mixed-ANOVA, p
Figure 2
Figure 2
Dysbiosis in patients with IBD. (A) Microbiome clustering based on unweighted (left) and weighted (right) Principal Coordinate Analysis-UniFrac metrics. Significant differences were observed between all controls (All-HC, combining HC, healthy relatives HR(CD) and HR(UC)) and patients with CD (NPMANOVA test; p=0.001 for weighted and unweighted UniFrac indexes) and between all controls and patients with UC (NPMANOVA test, p=0.001 for unweighted and p=0.004 for weighted UniFrac). Microbial richness was calculated based on the Chao1 index (B, left) and microbial richness and evenness on the Shannon index (B, right). Using the Student's t-test, the microbiome of patients with CD presented significantly lower richness and evenness than healthy controls (HC, HR(CD), and HR(UC)) and patients with UC, but patients in remission and in recurrence (CD-RC and UC-RC) did not present significant differences. *p
Figure 3
Figure 3
Calprotectin: biomarker of inflammation. Calprotectin was measured in the stool of healthy relatives of CD (HR(CD)) and UC (HR(UC)) patients, and in the stool of patients with CD and UC at baseline (TP0) and after 1-year in remission (RM) and at recurrence (RC). The Mann-Whitney test was used to compare differences between groups. CD, Crohn's disease.
Figure 4
Figure 4
Microbial marker discovery and validation. Eight bacterial genera showed potential to discriminate between HC (unrelated HC) and patients with CD and UC in the discovery cohort: 34 HC, and 33 patients with UC and 34 patients with CD (A) and in the validation cohort of 2045 faecal samples from HC (n=1247), CD (n=339), UC (n=158), IBS (n=202) and anorexia (n=99) (B). Each blue bar represents the presence of each microbial group for each subject. Participants in each group are underlined with a specific colour code (blue=all HC; red=CD; yellow=UC; green=IBS and purple=anorexia). The plot was performed using an R script on relative abundance of the eight bacterial genera. The gradient of colours for the bars corresponds to white=absent, clear blue=low abundance and dark=high abundance. (C) Unweighted UniFrac Principal Coordinate Analysis representation of the various groups of subjects: HC=unrelated healthy controls, CD, Crohn's disease, Significant differences were found between CD and HC, UC, IBS and anorexia (NPMANOVA test, p

Comment in

  • Gut microbiota: Diagnosing IBD with the gut microbiome.
    Dickson I. Dickson I. Nat Rev Gastroenterol Hepatol. 2017 Apr;14(4):195. doi: 10.1038/nrgastro.2017.25. Epub 2017 Mar 1. Nat Rev Gastroenterol Hepatol. 2017. PMID: 28250469 No abstract available.
  • A microbial signature for Crohn's disease.
    Çekin AH. Çekin AH. Turk J Gastroenterol. 2017 May;28(3):237-238. doi: 10.5152/tjg.2017.24031. Epub 2017 Apr 14. Turk J Gastroenterol. 2017. PMID: 28408358 No abstract available.
  • Guiding longitudinal sampling in IBD cohorts.
    Vázquez-Baeza Y, Gonzalez A, Xu ZZ, Washburne A, Herfarth HH, Sartor RB, Knight R. Vázquez-Baeza Y, et al. Gut. 2018 Sep;67(9):1743-1745. doi: 10.1136/gutjnl-2017-315352. Epub 2017 Oct 21. Gut. 2018. PMID: 29055911 Free PMC article. No abstract available.

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