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P835 Characterisation of fungal microbiota in a Norwegian IBD cohort

A. van Beelen Granlund*1,2, S. Thorsvik1,3, I. Catalán-Serra1,4, V. Beisvag2, D. Underhill1,5,6, A. K. Sandvik1,3

1Norwegian University of Science and Technology, Centre for Molecular Inflammation Research, Trondheim, Norway, 2Norwegian University of Science and Technology, Department of Clinical and Molecular Medicine, Trondheim, Norway, 3St Olav’s Hospital, Department of Gastroenterology, Trondheim, Norway, 4Levanger Hospital, Department of Medicine [Gastroenterology], Levanger, Norway, 5Cedars-Sinai Medical Center, Research Division of Immunology, Los Angeles, CA, USA, 6Cedars-Sinai Medical Center, F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, CA, USA

Background

While the role of bacterial microbiota in disease has been widely studied over the last years, the exact role of the mycobiome in IBD remains poorly understood. A few studies show changes in fungal microbiota associated with IBD status. However, there is little consensus regarding a definite fungal microbiome in IBD. The aim of this study was to characterise the fungal microbiota of patients, and to evaluate association between fungal abundance and patient characteristics.

Methods

The present study presents sequencing of the faecal fungi of 111 individuals (active CD (aCD = 22), active UC (aUC = 20), inactive CD (iCD = 15), inactive UC (iUC = 32), healthy controls (F = 22)). Patient characteristics (age, sex, medication, faecal calprotectin (fCalpro), faecal Neutrophil gelatinase-associated lipocalin (fNGAL), disease history) was available for all included individuals. ITS sequencing was done on amplicons targeting the ITS1 region of fungal DNA. Sequencing was done on a Illumina MiSeq sequencer. Filtered FASTQ sequencing data were aligned with the Targeted Host-associated Fungi (THF) database using Blast in QIIME. Chosen OTUs were compiled into six taxonomic ranks (Phylum-Species). Data analysis was performed in R, using tools of the phyloseq and deSeq2-packages.

Results

In contrast to other studies of fungal microbiota, we found no significant differences in either species or genus richness, diversity or evenness between IBD subgroups and healthy controls. There were several differences between sample groups on both genus and species level. Figure 1 shows top 10 differentially abundant genera (a) and species (b) for the contrast active IBD vs. healthy controls. Candida Albicans was significantly increased in aUC (logFC 5.4, adj. pVal < 0.001) but not in aCD (logFC 1.84, adj. pVal 0.2), while Cryptococcus tephrensis was significantly decreased in aCD (logFC -4.76, adj. pVal < 0.001) but not in aUC (logFC −0.96, adj. pVal 0.52). High levels of fNGAL was associated with increased abundance of the Aspergillus (adj. pVal < 0.001) genus, and decrease in Clavispora (adj. pVal < 0.001).

Figure 1. Top 10 genera (a) and species (b) for the contrast active IBD (aIBD) vs. healthy controls (F). Bars show mean log2 fold relative difference in abundance with standard error of the mean. p-values are adjusted for multiple comparison.

Conclusion

With its strictly controlled patient cohort and broad patient characteristics, our analysis serves as a rigorous addition to the understanding of IBD-associated changes in the fungal microbiome. We identify several novel changes in species and genera abundance associated with patient subgroups, disease activity and clinical parameters, further enhancing our understanding of the fungal microbiome in IBD.