{
  "abstract": "Background Crohn’s disease (CD) affecting different intestinal segments is treated as a single entity, yet whether disease location determines molecular phenotype independent of diagnosis remains unexplored. We aimed to determine whether ileal and colonic CD represent molecularly distinct entities and quantify the transcriptomic similarity between colonic CD and ulcerative colitis (UC).Methods Colonic biopsy gene expression profiles were integrated from three GEO cohorts (GSE75214, GSE179285, GSE16879; n=531; ileal CD=185, colonic CD=131, UC=215) following ComBat batch correction and projected onto a UMAP embedding derived from unsupervised consensus clustering (k=3) of 616 IBD transcriptomes. Differential expression (Welch’s t-test, FDR<0.05, |log2FC|>0.5) and MSigDB Hallmark pathway enrichment were performed for ileal CD vs colonic CD and colonic CD vs UC comparisons.Results Ileal and colonic CD occupied entirely distinct transcriptomic regions. A total of 84% of ileal CD samples mapped to the Metabolic-Absorptive subtype, while colonic CD distributed across Hypoxia-Metabolic (69%) and Inflammatory-EMT (31%) subtypes - identical to UC (62% and 38% respectively) ( IDDF2026-ABS-0222 Figure 1. Ileal CD vs colonic CD pathway enrichment).Differential expression identified 824 significant genes distinguishing ileal from colonic CD, versus only 46 genes separating colonic CD from UC, an 18-fold difference, confirming location as a far stronger determinant of molecular phenotype than diagnosis (IDDF2026-ABS-0222 Figure 2. Colonic CD vs UC pathway enrichment, IDDF2026-ABS-0222 Figure 3. Molecular subtype distribution by location, IDDF2026-ABS-0222 Figure 4. Colonic CD vs UC differential expression). Ileal CD was characterised by xenobiotic metabolism, bile acid processing, and fatty acid absorption pathways (p<2×10−10), consistent with terminal ileal absorptive dysfunction. Colonic CD upregulated MYC targets, unfolded protein response, and PI3K/AKT/mTOR signalling pathways shared with UC mucosal regeneration. Colonic CD retained a residual metabolic signature (fatty acid metabolism, p=4×10−6) distinguishing it from UC, but no inflammatory pathway separation was observed (IDDF2026-ABS-0222 Figure 5. Umap CD location vs UC).Conclusions Ileal and colonic CD are transcriptomically distinct diseases sharing only a clinical label. Colonic CD is molecularly near-identical to UC, with 18-fold fewer differentially expressed genes separating them than separate ileal from colonic CD. These findings challenge the anatomical agnosticism of current CD classification and suggest colonic CD may warrant reclassification, distinct treatment stratification, and separate inclusion in clinical trials.Abstract IDDF2026-ABS-0222 Figure 1Abstract IDDF2026-ABS-0222 Figure 2Abstract IDDF2026-ABS-0222 Figure 3Abstract IDDF2026-ABS-0222 Figure 4Abstract IDDF2026-ABS-0222 Figure 5",
  "authors": [
    {
      "affiliations": [
        "New York Medical College, United States"
      ],
      "name": "Jeril Lasington"
    },
    {
      "affiliations": [
        "Rutgers University, United States"
      ],
      "name": "Lawin Steve Mathew Lasington"
    },
    {
      "affiliations": [
        "Boston University, United States"
      ],
      "name": "Swamynathan Umamaheshwaran"
    }
  ],
  "title": "IDDF2026-ABS-0222 Crohn’s or colitis? when the transcriptome can’t tell the difference",
  "uid": "5fad8dd6-6ce0-5a98-9e8f-81049a0d3a56"
}