The ileal fungal microbiota is altered in Crohn's disease and is associated with the disease course

Maya Olaisen; Mathias L Richard; Vidar Beisvåg; Atle van Beelen Granlund; Elin S Røyset; Olivier Rué; Tom Christian Martinsen; Arne Kristian Sandvik; Harry Sokol; Reidar Fossmark

doi:10.3389/fmed.2022.868812

The ileal fungal microbiota is altered in Crohn's disease and is associated with the disease course

Front Med (Lausanne). 2022 Sep 27:9:868812. doi: 10.3389/fmed.2022.868812. eCollection 2022.

Authors

Maya Olaisen^{1

2}, Mathias L Richard^{3

4}, Vidar Beisvåg^{1

5}, Atle van Beelen Granlund^{1

6}, Elin S Røyset^{1

6

7}, Olivier Rué^{8

9}, Tom Christian Martinsen^{1

2}, Arne Kristian Sandvik^{1

2

6}, Harry Sokol^{3

4

10}, Reidar Fossmark^{1

2}

Affiliations

¹ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
² Department of Gastroenterology and Hepatology, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway.
³ INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France.
⁴ Paris Center for Microbiome Medicine, Fédération Hospitalo-Universitaire, Paris, France.
⁵ Central Administration, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway.
⁶ Centre of Molecular Inflammation Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁷ Department of Pathology, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway.
⁸ INRAE, MaIAGE, Université Paris-Saclay, Jouy-en-Josas, France.
⁹ INRAE, BioinfOmics, MIGALE Bioinformatics Facility, Université Paris-Saclay, Jouy-en-Josas, France.
¹⁰ Gastroenterology Department, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Sorbonne Université, Paris, France.

Abstract

Introduction: Fungal microbiota's involvement in the pathogenesis of Crohn's disease (CD) is incompletely understood. The terminal ileum is a predilection site both for primary involvement and recurrences of CD. We, therefore, assessed the mucosa-associated mycobiota in the inflamed and non-inflamed ileum in patients with CD.

Methods: The mucosa-associated mycobiota was assessed by ITS2 sequencing in a total of 168 biopsies sampled 5 and 15 cm proximal of the ileocecal valve or ileocolic anastomosis in 44 CD patients and 40 healthy controls (HC). CD patients with terminal ileitis, with endoscopic inflammation at 5 cm and normal mucosa at 15 cm and no history of upper CD involvement, were analyzed separately. The need for additional CD treatment the year following biopsy collection was recorded.

Results: CD patients had reduced mycobiota evenness, increased Basidiomycota/Ascomycota ratio, and reduced abundance of Chytridiomycota compared to HC. The mycobiota of CD patients were characterized by an expansion of Malassezia and a depletion of Saccharomyces, along with increased abundances of Candida albicans and Malassezia restricta. Malassezia was associated with the need for treatment escalation during follow-up. Current anti-TNF treatment was associated with lower abundances of Basidiomycota. The alpha diversity of the inflamed and proximal non-inflamed mucosa within the same patients was similar. However, the inflamed mucosa had a more dysbiotic composition with increased abundances of Candida sake and reduced abundances of Exophiala equina and Debaryomyces hansenii.

Conclusions: The ileal mucosa-associated mycobiota in CD patients is altered compared to HC. The mycobiota in the inflamed and proximal non-inflamed ileum within the same patients harbor structural differences which may play a role in the CD pathogenesis. Increased abundance of Malassezia was associated with an unfavorable disease course.

Keywords: Crohn's disease; fungal microbiota; fungi; inflammatory bowel disease; mycobiota.