Distal fecal wash host transcriptomics identifies inflammation throughout the colon and terminal ileum

Non-invasive modalities for assessing active endoscopic and histological inflammation in Crohn’s disease and Ulcerative Colitis patients are critically needed. Fecal wash host shed-cell transcriptomics has been shown to be a robust classifier of endoscopic and histological inflammation in inflammatory bowel disease (IBD) patients with distal colitis 1. Whether such fecal washes can inform on inflammatory processes occurring in more proximal intestinal segments is currently unknown. 59 IBD patients and 50 controls were prospectively enrolled. Biopsies and fecal washes from the distal colon, proximal colon and terminal ileum were compared. Host transcriptomics was performed on the biopsies and fecal washes obtained during colonoscopy at predefined locations throughout the colon and terminal ileum and results were associated with concurrent clinical, endoscopic and histological parameters. We found that host transcriptomics of distal fecal washes robustly classify histological inflammation in ileal and proximal colonic Crohn’s disease, even without distal colonic involvement (Area Under the Receiver Operating Characteristic Curve, AUC=0.94+-0.09). We further found that fecal washes consist of modules of co-expressed genes of immune, stromal and epithelial origin that are indicative of endoscopic disease severity. Fecal wash host transcriptomics also captures expression of gene modules previously associated with lack of response to biological therapies. Our study establishes the accuracy of distal colonic fecal washes for identifying and scoring inflammatory processes throughout the entire ileal-colonic axis. [Display omitted]