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

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

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.868812

DOI=10.3389/fmed.2022.868812

ISSN=2296-858X

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 <italic>Malassezia</italic> and a depletion of <italic>Saccharomyces</italic>, along with increased abundances of <italic>Candida albicans</italic> and <italic>Malassezia restricta</italic>. <italic>Malassezia</italic> 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 <italic>Candida sake</italic> and reduced abundances of <italic>Exophiala equina</italic> and <italic>Debaryomyces hansenii</italic>.</p></sec><sec><title>Conclusions</title><p>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 <italic>Malassezia</italic> was associated with an unfavorable disease course.</p></sec>