Exploring how microbiome signatures change across inflammatory bowel disease conditions and disease locations

Abstract

Understanding the variables that influence microbiome studies is critical for successful translational research. Inflammatory bowel disease (IBD) is a complex group of diseases that can present at multiple locations within the Gastrointestinal tract. Here, using the FAMISHED study cohort, we aimed to investigate the relationship between IBD condition, IBD disease location, and the microbiome. Signatures of the microbiome, including measures of diversity, taxonomy, and functionality, all significantly differed across the three different IBD conditions, Crohn's disease (CD), ulcerative colitis (UC), and microscopic colitis (MC). Notably, when stratifying by disease location, patients with CD in the terminal ileum were more similar to healthy controls than patients with CD in the small bowel or colon, however no differences were observed at different disease locations across patients with UC. Change in taxonomic composition resulted in changes in function, with CD at each disease location, UC and MC all having unique functional dysbioses. CD patients in particular had deficiencies in Short-Chain Fatty Acid (SCFA) pathways. Our results demonstrate the complex relationship between IBD and the microbiome and highlight the need for consistent strategies for the stratification of clinical cohorts and downstream analysis to ensure results across microbiome studies and clinical trials are comparable.

Figure 1

(A) Overview of FAMISHED Patient cohort. (B) NMDS ordination plot based on the Bray Curtis dissimilarity between Healthy Controls and three IBD conditions, CD, MC, UC. (C) The Observed ASV diversity of Healthy Controls and patients classified as having IBD. (D) The Observed ASV diversity of Healthy Controls and patients classified as having CD, UC, and MC. (E) The Observed ASV diversity of Healthy Controls and patients classified as having CD, UC, and MC when accounting for disease location in CD and UC patients.

Figure 2

(A) Cladogram demonstrating taxa which are enriched in each patient group when comparing Healthy Controls and CD patients. (B) Cladogram demonstrating taxa which are enriched in each patient group when comparing Healthy Controls and CD patients when accounting for disease location. (C) Changes in metabolic pathways between Healthy Controls and CD Patients. (D) Changes in metabolic pathways between Healthy Controls and CD patients when accounting for disease location.

Figure 3

(A) Cladogram demonstrating taxa which are enriched for UC or Healthy Controls. (B) Changes in metabolic pathways between healthy volunteers and UC patients.