{
  "abstract": "Background and AimsFibrostenotic stricture is a severe complication of Crohns disease (CD) that affect up to 50% of patients over their lifetime, causing irreversible narrowing of the intestinal lumen and bowel obstruction, but the molecular programs that distinguish stenotic from non-stenotic inflammation and the relative contributions of fibrosis and smooth-muscle remodeling remain incompletely characterized. We aimed to dissect bowel-wall compartment-specific and histology-defined remodeling programs in fibrostenotic CD.\n\nMethodsMatched full-thickness terminal ileal tissues from 4 patients with fibrostenotic CD were sampled from stenotic stricture (SS), non-stenotic inflamed bowel (NS), and non-inflamed bowel (NI). Histomorphology-guided NanoString GeoMx whole-transcriptome profiling was performed across mucosa, muscularis mucosae, submucosa, and muscularis propria. GeoMx data were processed by standard software provided by GeoMx platform. DESeq2 models included patient identity as a blocking factor, and the analysis was performed in 74 histologically valid regions of interest (ROIs) representing full spectrum of CD histopathologies. DEGs were defined as adjusted P < .05 and |log2FC| >= 1.0.\n\nResultsOut of 18,677 genes analyzed in each of the ROIs, direct SS-versus-NS comparison identified 0 significant DEGs in mucosa, 18 in muscularis mucosae, 43 in submucosa, and 0 in muscularis propria. NS-versus-NI submucosa showed 132 DEGs (131 increased, 1 decreased), dominated by humoral/plasma-cell genes with a modest stromal-remodeling component. SS-versus-NI submucosa showed 144 DEGs (138 increased, 6 decreased) with coordinated contractile, extracellular-matrix/remodeling and cell-matrix adhesion programs. Muscularized versus fibrotic SS submucosa showed 219 DEGs, with marked enrichment of contractile and remodeling genes in muscularized regions. Excluding 5 follicle-containing submucosal ROIs markedly altered the NS comparison but not the core SS fibromuscular program. Exploratory follicular-niche analyses showed that lymphoid follicle-rich (LFR) submucosa was lymphoid/B-cell enriched relative to lymphoid follicle-null (LFN) areas; SS-LFR nevertheless acquired a stronger fibroblast/ECM program relative to NS-LFR, while CCL19 was the only significant LFR-versus-LFN DEG within SS.\n\nConclusionsFibrostenotic CD is characterized by spatially concentrated submucosal fibromuscular remodeled inflammatory program. Non-stenotic submucosa is heterogeneous and may already show regional stromal remodeling, whereas established stenosis displays a broader and more robust ECM-contractile-adhesion phenotype with molecularly distinct fibrotic and muscularized niches.",
  "abstract_shown": true,
  "affiliations": [
    "Wake Forest University School of Medicine"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "X. Gui"
    },
    {
      "name": "G. Jin"
    },
    {
      "name": "D. L. Caudell"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f2em1h7ez8311.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.14.26363080",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.14.26363080v1.full",
  "id": "f2em1h7ez8311",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.14.26363080v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "gastroenterology"
    ],
    [
      "openalex",
      "1311|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W7213272824",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.14.26363080v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f2em1h7ez8311.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:39Z",
      "native_id": "10.64898/2026.09.14.26363080",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.14.26363080v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Inflammatory Bowel Disease",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Layer-Resolved Spatial Transcriptomic Profiling Reveals Distinct Fibrotic and Muscularizing Submucosal Niches in Fibrostenotic Crohn's Disease",
  "title_text": "Layer-Resolved Spatial Transcriptomic Profiling Reveals Distinct Fibrotic and Muscularizing Submucosal Niches in Fibrostenotic Crohn's Disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:39Z",
  "url": "https://research.draconitic.com/paper/f2em1h7ez8311",
  "venue": "medRxiv",
  "versions": []
}