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

Abstract

IntroductionFungal 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.MethodsThe 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.ResultsCD 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.ConclusionsThe 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.

Changes in the gut mycobiome in pediatric patients in relation to the clinical activity of Crohn's disease

“…In this study, we have documented that CD patients were over-colonized with Malassezia species compared to the control group (Figures 2 and 3 ). This is consistent with the observations of other researchers[ 12 , 27 , 46 ]. Patients with CD often suffer from malabsorption syndrome, manifested by fatty diarrhea.…”

“…, lower number of taxons in a single sample. These data are consistent with previous reports[ 24 , 26 , 27 ]. Interestingly, we have shown that patients in the non-active phase of CD (II) were characterized by significantly higher alpha biodiversity indices at the level L7 (species) compared to patients with newly diagnosed, active disease (Ia).…”

“…Analysis at the species level has shown that C. albicans constituted the highest percentage in the group of patients in remission (II) compared to the other groups (Figure 3 ), and LDA analysis has documented that this species may be a fungal biomarker for patients in non-active CD ( P = 0.005, Figure 4 ). Previous studies showed that these yeasts were more abundant in CD patients, and it was suggested that C. albicans may promote IBD by increasing the inflammatory response[ 27 , 32 , 33 ]. However, it should be noted that these studies did not take into account patients in remission.…”

Unveiling Candida albicans intestinal carriage in healthy volunteers: the role of micro- and mycobiota, diet, host genetics and immune response

“…The abundance of this fungal species has been previously shown to decrease in patients suffering from inflammatory bowel disease (IBD), while C. albicans abundance tends to increase, thus suggesting a negative association between the two fungal species. 31 , 32 This discrepancy between these results and our findings suggests that although competition between C. albicans and S. cerevisiae may arise in the context of a disease, such competition is not relevant in the healthy intestinal niche.…”

Insight into the mechanism of gallstone disease by proteomic and metaproteomic characterization of human bile

“…Reoviridae (Duplornaviricota, Reovirales, Resentoviricetes, Rotavirus) has been commonly implicated in biliary atresia, a childhood disease ( Averbukh and Wu, 2018 ). Among the fungal taxa, Debaryomyces has been previously identified in the human digestive tract and associated with Crohn’s disease ( Olaisen et al, 2022 ), while Sordariomycetes (Hypocreales) was found in skin microbiome ( Oh et al, 2016 ).…”