Fungal Microbiota Composition in Inflammatory Bowel Disease Patients: Characterization in Different Phenotypes and Correlation With Clinical Activity and Disease Course

Ignacio Catalán-Serra; Silje Thorsvik; Vidar Beisvag; Torunn Bruland; David Underhill; Arne Kristian Sandvik; Atle van Beelen Granlund

doi:10.1093/ibd/izad289

Fungal Microbiota Composition in Inflammatory Bowel Disease Patients: Characterization in Different Phenotypes and Correlation With Clinical Activity and Disease Course

Inflamm Bowel Dis. 2023 Dec 16:izad289. doi: 10.1093/ibd/izad289. Online ahead of print.

Authors

Ignacio Catalán-Serra^{1

2

3}, Silje Thorsvik^{1

2}, Vidar Beisvag², Torunn Bruland^{2

4}, David Underhill^{1

5

6}, Arne Kristian Sandvik^{1

2

4}, Atle van Beelen Granlund^{1

2

4}

Affiliations

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

PMID: 38103028
DOI: 10.1093/ibd/izad289

Abstract

Background: There is growing evidence of the role of the mycobiome in inflammatory bowel disease (IBD). Variations within phenotypes and activity and with prognosis have been poorly studied.

Methods: A total of 111 individuals were prospectively enrolled: 89 IBD patients (52 ulcerative colitis and 37 Crohn's disease [CD]) and 22 healthy individuals. Disease characteristics were collected and a fecal calprotectin >100 μg/mg was considered indicative of activity. A subset of patients was followed for 6 ± 2 years. Disease course was designated as either complicated or uncomplicated based on the need of intensified medication and/or surgery. ITS sequencing was performed targeting the ITS1 region.

Results: We found lower Ascomycota/Basidiomycota ratio in IBD. Patients showed a marked increase in Candida dublinensis and Ca albicans and were depleted of Aspergillus rubrobrunneus and Penicillium brevicompactum (P ≤ .001) Saccharomyces was predominant in total colitis and Penicillium in proctitis. Several Penicillium species were depleted in total colitis vs proctitis. Ileal CD patients were enriched in Debaromyces hansenii and depleted of Ca tropicalis (P ≤ .001). Ca albicans was overrepresented in inflammatory (B1) vs fibrostenosing (B2) CD. Ca dublinensis was more abundant in active patients and correlated positively with fecal calprotectin and neutrophil gelatinase-associated lipocalin, while S pastorianus correlated inversely with activity. Ca sake was associated with complicated disease and increased abundance of Cryptococcus carnescens with the need for surgery in CD.

Conclusions: This study shows important differences in the mycobiome in IBD and within phenotypes. Selected fungal species were associated with complicated disease and the need of surgery in CD. This work adds to our understanding of the role of fungi in IBD, with potential clinical implications.

Keywords: Crohn's disease; fungi; inflammatory bowel disease; microbiology; microbiome; mycobiome; ulcerative colitis, prognosis.

Plain language summary

This study compares the fungal microbiome (mycobiome) between patients with inflammatory bowel disease (IBD) (ulcerative colitis and Crohn’s disease [CD]) and control individuals in a well-characterized population in Norway. We show important differences in the mycobiome of IBD patients and between ulcerative colitis and CD. Our study also demonstrates variations in the fungal composition in the different disease phenotypes (regarding disease location or behavior of disease). Last, we show that selected fungal species are associated with the activity of the disease, the future development of complications and the need of surgery in CD. This work adds to our understanding of the role of fungi in IBD and has potential clinical implications.