Transcriptomic profiling of fecal aspirates as a tool for prediction of endoscopic inflammation in small bowel...

While colonoscopy with mucosal biopsies remains the gold standard for evaluation and surveillance of Crohn's disease (CD), it does not allow a full evaluation of inflammation status over the entire small bowel. This study aims to evaluate the efficacy of host transcriptomics of fecal aspirates in assessing small bowel inflammation in asymptomatic CD patients.

Biopsies and fecal aspirate samples were prospectively obtained from CD patients in clinical remission undergoing same-day colonoscopy and video-capsule endoscopy (VCE). Host transcriptomics analysis was performed, and findings were associated with clinical, laboratory, and endoscopic parameters, and validated using a 2-gene-based qRT-PCR assay.

Our cohort comprised 56 asymptomatic Crohn's patients and 16 healthy controls. Thirty-five asymptomatic patients (62.5%) demonstrated active inflammation by colonoscopy or VCE. Transcriptomic analysis of fecal aspirates distinguished inflamed from noninflamed patients, revealing substantially more differentially expressed genes than biopsies (2352 vs 22, respectively). Inflamed aspirates showed enrichment of natural killer and regulatory T cells, along with activation of immune pathways. We devised a 10-gene predictive model for endoscopic inflammation in asymptomatic Crohn's patients with superior discrimination compared to stool calprotectin (AUC = 0.82 vs 0.58) and closely approximates the accuracy of VCE (AUC = 0.90). An additional 10-gene diagnostic model differentiated CD patients from healthy controls (AUC = 0.952). Both models were validated using qRT-PCR as well as an additional validation cohort.

Transcriptomic profiling of rectal fecal aspirates reliably detects small bowel inflammation and identifies specific immune pathways in asymptomatic CD. The resulting models offer potential biomarkers for CD diagnosis and monitoring.