Fecal microbial composition of ulcerative colitis and Crohn's disease patients in remission and subsequent exacerbation - PubMed (original) (raw)

Fecal microbial composition of ulcerative colitis and Crohn's disease patients in remission and subsequent exacerbation

Edgar S Wills et al. PLoS One. 2014.

Abstract

Background: Limited studies have examined the intestinal microbiota composition in relation to changes in disease course of IBD over time. We aimed to study prospectively the fecal microbiota in IBD patients developing an exacerbation during follow-up.

Design: Fecal samples from 10 Crohn's disease (CD) and 9 ulcerative colitis (UC) patients during remission and subsequent exacerbation were included. Active disease was determined by colonoscopy and/or fecal calprotectine levels. Exclusion criteria were pregnancy, antibiotic use, enema use and/or medication changes between consecutive samples. The microbial composition was assessed by 16S rDNA pyrosequencing.

Results: After quality control, 6,194-11,030 sequences per sample were available for analysis. Patient-specific shifts in bacterial composition and diversity were observed during exacerbation compared to remission, but overarching shifts within UC or CD were not observed. Changes in the bacterial community composition between remission and exacerbation as assessed by Bray-Curtis dissimilarity, were significantly larger in CD versus UC patients (0.59 vs. 0.42, respectively; p = 0.025). Thiopurine use was found to be a significant cause of clustering as shown by Principal Coordinate Analysis and was associated with decreases in bacterial richness (Choa1 501.2 vs. 847.6 in non-users; p<0.001) and diversity (Shannon index: 5.13 vs. 6.78, respectively; p<0.01).

Conclusion: Shifts in microbial composition in IBD patients with changing disease activity over time seem to be patient-specific, and are more pronounced in CD than in UC patients. Furthermore, thiopurine use was found to be associated with the microbial composition and diversity, and should be considered when studying the intestinal microbiota in relation to disease course.

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Conflict of interest statement

Competing Interests: MP has acted as a consultant for MSD and received payments for lectures from MSD, Falk, Pharma, Abvie and Ferring. The other authors have declared that no competing interests exist. The authors can confirm that the competing interests that they have declared do not alter their adherence to all PLOS ONE policies on sharing data and materials.

Figures

Figure 1

Figure 1. Relative abundance of bacterial phyla in fecal samples of nine UC (#1–9) and ten CD (#10–19) patients during remission and subsequent exacerbation.

Figure 2

Figure 2. Mean number of observed species (OTUs) according to thiopurine use in Crohn’s disease (p = 2.57*10

−5 ), total Inflammatory Bowel Disease (p = 2.37*10 −4 ) and Ulcerative Colitis (p = 7.93*10 −4 ) patients. *: Significantly different (p<0.001).

Figure 3

Figure 3. Communities clustered using Principal Coordinates Analysis (PCoA) of the unweighted UniFrac distance matrix.

(A) PC1 and PC2 are plotted on _x_- and _y_-axes. Each point corresponds to a community colored according to thiopurine use. All samples are shown. The percentage of variation explained by the plotted principal coordinates is indicated on the axes. (B) PC1 and PC3 are plotted on x- and y-axis. Each point corresponds to a community colored according to disease location. Only samples from UC patients are included.

Figure 4

Figure 4. Within and between subjects pair-wise unweighted UniFrac distances for ulcerative colitis (#1–9) and Crohn’s disease (#10–19) patients.

Figure 5

Figure 5. Mean within subjects pair-wise Bray-Curtis distances for ulcerative colitis and Crohn’s disease patients (p = 0.027).

*: Significantly different (p<0.05).

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This study was financially supported by grants form the Academic Foundation of Maastricht University Medical Center+ and by the IBD Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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