{
  "abstract": "Background Clinical remission in IBD is defined by symptom resolution and endoscopic normalisation, yet whether the mucosa returns to a truly healthy molecular state remains unknown. We aimed to characterise the residual transcriptomic footprint of uninflamed IBD mucosa versus healthy controls.Methods Gene expression profiles from four integrated GEO cohorts (n=616) spanning three groups, truly healthy controls (n=41), uninflamed IBD mucosa (n=31), and active IBD (n=544), were batch-corrected using ComBat and projected onto a common UMAP embedding. Differential expression (Welch’s t-test, FDR<0.05, |log2FC|>0.3), MSigDB Hallmark pathway enrichment, a 47-gene Fibrosis Risk Score (FRS), and 13-cell-type Total Immune Burden Score (TIBS) were computed across groups.Results UMAP projection revealed uninflamed IBD mucosa occupying an intermediate molecular position distinct from truly healthy controls and active IBD, clustering within metabolic C1/C2 subtype space yet failing to co-localise with healthy controls ( IDDF2026-ABS-0267 Figure 1. UMAP projection of control types in molecular subtype space). Uninflamed IBD mucosa harboured 479 significantly differentially expressed genes versus truly healthy controls, including upregulation of MMP1 (+1.02), MMP3 (+0.87), IDO1 (+0.80), DUOX2 (+0.65), and CXCL10 (+0.60) (IDDF2026-ABS-0267 Figure 6. Top 20 differentially expressed genes). Volcano plot analysis confirmed widespread residual transcriptomic dysregulation, with more genes upregulated in uninflamed IBD than healthy controls across the full expression range (IDDF2026-ABS-0267 Figure 3. Volcano plot of 479 differentially expressed genes in uninflamed IBD mucosa versus truly healthy controls). Pathway enrichment revealed persistent upregulation of Inflammatory Response (p=1.2×10−7), Complement (p=1.9×10−4), and mTORC1 signalling in uninflamed mucosa, while healthy mucosa was enriched for Fatty Acid Metabolism (p=7×10−9), Peroxisome function, and Oxidative Phosphorylation (IDDF2026-ABS-0267 Figure 4. MSigDB Hallmark pathway enrichment comparing uninflamed IBD versus truly healthy mucosa).Critically, FRS was significantly elevated in uninflamed IBD versus healthy controls (-0.408 vs -0.743; p<0.0001) (IDDF2026-ABS-0267 Figure 2. Fibrosis Risk Score (FRS) distribution across truly healthy and uninflamed IBD-context and active IBD groups), while TIBS was not significantly different (p=0.261) (IDDF2026-ABS-0267 Figure 5. Total immune burden score TIBS distribution), demonstrating fibrotic programming persists after immune normalisation. Top differentially expressed genes formed a continuous gradient from healthy to uninflamed to active IBD, with MMP1 and MMP3 progressively increasing and absorptive signatures progressively decreasing (IDDF2026-ABS-0267 Figure 6. Top 20 differentially expressed genes).Conclusions Endoscopic remission in IBD does not restore normal mucosal gene expression. Fibrotic programming persists in histologically normal mucosa despite immune normalisation, with 479 genes remaining dysregulated versus truly healthy controls. These findings reframe remission as a midpoint on a molecular continuum rather than a return to baseline, suggesting current remission endpoints are insufficient and fibrosis-targeted therapies may be warranted even in patients achieving endoscopic remission.Abstract IDDF2026-ABS-0267 Figure 1Abstract IDDF2026-ABS-0267 Figure 2Abstract IDDF2026-ABS-0267 Figure 3Abstract IDDF2026-ABS-0267 Figure 4Abstract IDDF2026-ABS-0267 Figure 5Abstract IDDF2026-ABS-0267 Figure 6",
  "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-0267 The mucosa remembers: is endoscopic remission in IBD a molecular dead end?",
  "uid": "8bf067d6-f86b-5849-8a85-feb36ea3c262"
}