To Örebro University

Background: Inflammatory bowel disease (IBD) is a chronic disease where the aetiology is suggested to involve genetic, microbial, and environmental factors as well as their interactions. Though the bacterial component of the gut microbiome has been of substantial interest in recent years, the mycobiome (fungal community) is less studied. Recent studies have, however, shown that the efficacy of faecal microbiota transplantation in ulcerative colitis (UC) is dependent on the pre-transplantation of host mycobiome. Furthermore, there is an association between anti-Saccharomyces cerevisiae antibodies (ASCA) for Crohn’s disease (CD), but not UC. We aimed to characterize the gut mycobiome of incident IBD patients.

Methods: In this study, we analysed samples from 216 adult treatment-naïve patients in the NORDTREAT cohort, who were referred on suspicion of IBD. Patients were recruited in 4 Nordic countries from 2022 to 20231. The diagnosis of IBD was based on internationally accepted criteria (UC n=72, CD n=48 and IBD-unclassified [IBD-U] n=8) or, if IBD was ruled out, categorized as symptomatic controls (SC, n=88). Stool samples and colonic biopsies were collected at inclusion. From these, DNA was extracted, and ITS2 amplicon sequencing was performed as previously described2. The primary end-point of subsequent bioinformatic analysis was relative abundance at the genus level. The secondary end-points were alpha and beta diversity, as well as a correlation analysis between faecal samples and biopsies.

Results: The relative abundance at genus level was dominated by Saccharomyces in stool samples whereas this genus was markedly reduced in biopsies and Malassezia was found to be increased (see figure 1, data not shown for IBD-U). We did not observe statistically significant differences in relative abundance between patient groups. Alpha diversity and beta diversity did not significantly differ for fungi across patient groups, neither in stool nor in biopsies. However, canonical correspondence analysis of the dominant genera between biopsies and faecal samples demonstrated a low constrained proportion in SC (0,2), increasing from UC (0,25) through CD (0,5) indicating that in CD, the mycobiome of stool and mucosa is more similar than in the UC and SC.

Conclusion: This study of the gut mycobiome in new onset and treatment naïve IBD patients is the largest so far and does not find evidence of disease specific differences. Previous reports with inconsistent findings regarding alterations of the mycobiome in IBD patients might rather reflect treatment effects than a role of the mycobiome in disease aetiology.

References:

1.Fejrskov A, Füchtbauer JD, Davíðsdóttir LG, et al. Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease: protocol for the Nordic inception cohort study (NORDTREAT). BMJ Open. 2024;14(5):e083144. doi:10.1136/bmjopen-2023-083144

2.Rühlemann MC, Solovjeva MEL, Zenouzi R, et al. Gut mycobiome of primary sclerosing cholangitis patients is characterised by an increase of Trichocladium griseum and Candida species. Gut. Published online October 25, 2019. doi:10.1136/gutjnl-2019-320008