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P858 Crohn’s disease is characterised by a fungal dysbiosis

A. Frau1*, D. Jonkers2, J. Penders2, M. Pierik2, U.Z. Ijaz3, B. Campbell1, A. Darby4, J. Kenny4, N. Hall5, C. Probert1

1University of Liverpool, Cellular and Molecular Physiology, Liverpool, UK, 2Maastricht University, Internal Medicine, section of Gastroenterology, Maastricht, The Netherlands, 3University of Glasgow, Infrastructure and Environment, Glasgow, UK, 4University of Liverpool, Functional and Comparative Genomics, Liverpool, UK, 5Earlham Institute, Norwich, UK

Background

A role for fungi in Crohn’s disease (CD) has been proposed since the observation of ASCA antibodies in CD patients. In addition, genetic studies on inflammatory bowel disease patients found SNPs in genes involved in the immune response towards fungi. Recently, the detection of volatile organic compounds (VOCs) related to fungal metabolism in CD patients supports the idea that fungi are metabolically active in the gut of CD patients. Studies focused on the characterisation of the fungal community in CD patients have reported a dysbiosis, with an increase in Candida. New research on mouse models implies Saccharomyces as a cause in gut inflammation. However, our understanding of the role of fungi in IBD is limited.

Aim: to characterise the fungal community in a cohort of CD patients from the Netherlands over time.

Methods

Repeated faecal samples (2–3 samples/individual) were collected from 24 CD patients with either a stable or changing disease course and from 15 healthy controls, resulting in a total of 108 samples for downstream analysis.

Metagenomic DNA was extracted from stool samples with the PSP Spin Stool DNA kit (STRATEC) and used as template for fungal 18S rRNA amplification, amplicons were sequenced with an Illumina MiSeq (2 × 250 bp). Reads were quality filtered, trimmed, paired and OTUs were clustered. OTU table, fasta file, phylogenetic tree and metadata were then used for statistical analysis (taxa summary, alpha diversity, β diversity, phylogenetic dispersion, taxa differential analysis etc.).

Results

CD patients show a less diverse community than controls (alpha diversity, richness, pair-wise ANOVA, p < 0.05). NMDS analysis (unweighted Unifrac) shows a significant separation of CD active vs. CD remission vs controls (PERMANOVA, p = 0.001). Taxa differential analysis showed that Candida, Pichia and Cyberlindnera are overrepresented in CD, while Geotricum was overrepresented in controls. In general, Saccharomyces was dominant in almost all the samples. Unweighted phylogenetic dispersion indicates that CD patients have a more conserved community than controls (pair-wise ANOVA, p < 0.001).

Conclusion

Our study shows that a dysbiosis occurs in CD patients. Mycobiome in CD is less diverse, forms a separate cluster and is phylogenetically more conserved, indicating that the disease represents an environmental pressure driving the community toward phylogenetic clustering. Saccharomycetales are again protagonists. Candida, Pichia, and Cyberlindnera were overrepresented in CD suggesting they play a role in the inflammation or find inflamed gut a suitable environment. Further experimental studies (in vitro and in vivo models) are required to confirm the role of these species in Crohn’s disease.