{
  "abstract": "Background: Numerous baseline mucosal transcriptomic signatures have been proposed to stratify therapeutic outcomes in ulcerative colitis (UC), but cross-cohort transferability is frequently undermined by platform heterogeneity, endpoint/timepoint differences, and drug-specific biases. The resulting lack of a biologic-agnostic molecular baseline has limited clinical translation and prospective trial design.\n\nMethods: We integratively re-analyzed endpoint-linked baseline mucosal transcriptomes from seven public UC GEO series (778 unique baseline samples), with three additional public accessions used for disease-activity and contextual analyses. The primary response/healing synthesis used five study slices spanning anti-TNF, anti-integrin, and etrolizumab-treated cohorts. Unsupervised decomposition identified baseline endotypes, and endotype-outcome associations were estimated within each cohort (OR per 1-SD increase) and summarized by random-effects cross-cohort pooling with heterogeneity reporting, rank/seed sensitivity analyses, endpoint-restricted summaries, and negative controls.\n\nResults: Across five primary response/healing study slices, an epithelial barrier endotype (EPITHELIAL_BARRIER/NMF_C3) was associated with higher odds of response/healing (random-effects cross-cohort pooling OR = 3.171, 95% CI 1.491–6.744), whereas macrophage-inflammation and lymphoid/complement-stromal axes (MACROPHAGE_INFLAMMATION/NMF_C1 and LYMPHOID_COMPLEMENT_STROMAL/NMF_C2) were associated with lower odds of response/healing (OR = 0.359, 0.175–0.735; OR = 0.378, 0.220–0.651). The epithelial estimate was largest in GSE73661 but remained significant in the five-study leave-one-out summary after excluding that cohort (OR = 2.547, 95% CI 1.271–5.105). Cross-mechanism evaluation included UNIFI ustekinumab week-8 mucosal healing (UST arm n = 358; EPITHELIAL_BARRIER OR = 4.483, 2.263–8.881) and directionally consistent effects in etrolizumab. Endotype axes were supported by independent single-cell localization (FDR = 0.0026). Treatment-interaction tests were imprecise and did not establish drug-class-specific prediction. In cohort-heldout prediction, AUC ranged from 0.717 to 0.758, but calibration was variable. A network-based therapeutic prioritization was enriched for UC-approved agents (AUC = 0.741; permutation p = 6.0 × 10 ⁻ ⁴ ) and is presented as hypothesis-generating.\n\nConclusion: Baseline mucosal endotypes stratify healing capacity and therapeutic outcomes across public cohorts, with orthogonal support from single-cell localization. These findings support prospective evaluation as biologic-agnostic outcome stratifiers rather than established drug-specific predictive biomarkers.",
  "abstract_shown": true,
  "affiliations": [
    "School of Medicine, Quanzhou Medical College",
    "Key Laboratory of Screening and Control of Infectious Diseases (Quanzhou Medical College)"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Wenbiao Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shiyong Zeng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dwbrv3fhv70mp.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1931118",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1931118/full",
  "id": "dwbrv3fhv70mp",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1931118/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RM1-950"
    ],
    [
      "openalex",
      "1311|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W7223287045",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1931118/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dwbrv3fhv70mp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1931118",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1931118/full"
    },
    {
      "first_seen": "2026-10-30T13:43:13Z",
      "native_id": "de94cd8b88bc41b5aada76a9a68b312e",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fphar.2026.1931118"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Inflammatory Bowel Disease",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Baseline mucosal transcriptomic endotypes stratify healing capacity and biologic therapy outcomes in ulcerative colitis: an integrative multi-cohort study",
  "title_text": "Baseline mucosal transcriptomic endotypes stratify healing capacity and biologic therapy outcomes in ulcerative colitis: an integrative multi-cohort study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:13Z",
  "url": "https://research.draconitic.com/paper/dwbrv3fhv70mp",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}