P1091 Cross-domain dynamics of the fungal-bacterial microbiome in patients with ulcerative colitis

Abstract

Abstract Background Background: Candida in the gut has been recently linked to inflammatory activity in UC. However, the relationship between Candida abundance and the bacterial microbiome remains poorly understood, and how these relationships evolve over disease course in UC is unknown. Methods Methods: We utilized data from the Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD) from IBD Plexus to examine the taxonomic composition of the fungal mycobiome and bacterial microbiome cross-sectionally and longitudinally in time. Differential abundance was assessed using a log-transformed linear model on microbial relative abundances, with a false discovery rate of <0.25. Spearman’s correlations and co-abundance networks were utilized to examine relationships between fungi, bacteria, and disease activity. Changes in fungi and bacteria within-subjects was assessed over 2 timepoints, with respect to clinical inflammatory status, and abundances were compared using Wilcoxon signed rank tests. Results Results: Among 212 patients with UC, 166 patients were in clinical remission (78.3%) while 46 demonstrated clinical activity (21.7%). During clinical activity, there were increases in Candida (q-val<0.05), bacterial family Desulfovibrionaceae (q-val<0.05), and genus Bilophilia (q-val<0.05) [Fig 1A]. During remission, there were reductions in Candida, with increases in family Lachnospiraceae (q-val<0.05), including genus Anaerostipes (q-val=0.09), Blautia (q-val=0.09) and Roseburia (q-val=0.21) [Fig 1B]. Active disease positively correlated with Candida and Desulfovibrionaceae, and negatively correlated with family Lachnospiraceae. During remission, a positive network was present between family Lachnospiraceae, Bifidobacteriaceae, and Eggerthellaceae, which was disrupted during activity, while an antagonistic relationship was evident between Candida and Saccharomyces during remission. Among 25 patients with persistent remission over time (median time interval ~ 4 months), there were no changes in fungal abundances over timepoints. Among patients evolving from activity to remission (n=7), Saccharomyces significantly increased (p-val<0.05), with no significant change in Candida, although there was a trend towards reduction (mean relative abundance at t1=0.28 vs t2=0.11). Concurrently among bacteria, both Bifidobacterium and Anaerostipes significantly increased (p-val<0.05). Conclusions Candida and bacteria from families Lachnospiraceae may have opposing associations with inflammatory status in ulcerative colitis, suggesting they may demonstrate competitive ecological niches. Whether reduction of Candida species may expand protective bacteria should be tested adjunctive to immunosuppressive or microbial modulation therapies.