DIFFERENTIAL ABUNDANCE OF THE FUNGAL MYCOBIOME IN PATIENTS WITH ULCERATIVE COLITIS

Abstract BACKGROUND The fungal mycobiome has been increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Circulating antibodies to Saccharomyces antibodies are detected in 60-70% of Crohn’s disease and in 10-15% of patients with ulcerative colitis (UC). Specific fungal species, including Candida albicans, are increased in active IBD compared to healthy controls. Recently, UC patients with high fecal Candida prior to fecal microbial transplantation (FMT) were more likely to demonstrate robust treatment responses to transplant, with low Candida levels post-FMT predicting ameliorated inflammation in the recipient. Despite the accumulation of findings supporting the role of fungi in IBD, the mycobiome remains poorly characterized in UC. Few studies have examined changes in the UC mycobiome with respect to validated endoscopic indices or histologic parameters; furthermore, the effects of treatment exposure, including biologic medications, on fungal communities in UC are unknown. AIMS In this study, we aim to characterize the fungal mycobiome in UC patients with varying levels of endoscopic activity, endo-histologic activity, and treatment exposure. METHODS We performed a secondary analysis using the data extracted from the Crohn’s and Colitis Foundation’s Study of a Prospective Adult Research Cohort with IBD, which contains clinical, endoscopic, histologic, and metagenomic data. Using Internal Transcribed Spacer based deep sequencing of fungal rDNA from fecal samples, we classified sequences utilizing the UNITE fungal database and a fitted classifier. The R package DESeq2 was used to calculate the log-2 fold change of differential abundance. RESULTS We identified 504 unique fungal amplicon sequence variants across the cohort of 98 patients, belonging to phylum Ascomycota (71.5%), Basidiomycota (11%), Mucoromycota (0.16%), or unidentified (17.2%). Compared to endoscopic remission, patients with endoscopic activity (n=25) were enriched with Saccharomyces (4.31, p< 5 x 10-5) and Candida (2.53, p< 1 x 10-3). Similarly, compared to endo-histologic remission, patients with endo-histologic activity (n=19) were also enriched for Saccharomyces (2.71, p<0.05) and Candida (2.07, p=0.05). Biologic exposure favored the growth of Candida (p-adj < 1 x10-4). After adjusting for age, gender, and biologic exposure among patients with endoscopic activity, Saccharomyces (p-adj < 5 x 10-12) and Candida (p-adj< 1 x 10-8) remained enriched. CONCLUSION These data demonstrate that endoscopic and histologic inflammation in UC is associated with expansion of Saccharomyces and Candida compared to remission, even after controlling for exposure to biologic exposure. These findings are recapitulated during endo-histologic activity. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in UC should be evaluated.