{
  "abstract": "Several inherited predispositions to colorectal cancer exist, most notably familial adenomatous polyposis (FAP), which typically involves a germline loss-of-function mutation in one APC allele. A second hit in APC or related loci leads to aberrant Wnt signalling, triggering adenoma formation with near-complete penetrance. Yet, substantial variability in disease onset and severity, even among siblings with identical APC germline mutations, implicates environmental modifiers. Emerging evidence points to the gut microbiome as a critical regulator of adenoma initiation and progression, particularly in early-onset CRC. Here, we show that bacterial invasion is associated with neutrophil immunosuppression, T-cell exclusion and adenoma progression in a porcine model of FAP. Longitudinal mapping of progressing and regressing polyps using single-cell RNA sequencing, spatial transcriptomics and integrated microbiome profiling resolved the cellular and microbial architecture underlying these divergent lesion states. Single-cell RNA-seq identified 35 cell subpopulations and showed that regressing polyps are enriched for central-memory CD4+ T cells, cytotoxic CD8+ T cells and inflammatory neutrophils, whereas progressing polyps contain immunosuppressive/PD-L1-associated neutrophils, regulatory and dysfunctional T cells. Spatial transcriptomics with a custom host panel and targeted bacterial probes linked bacterial-high adenomatous regions to immunosuppressive neutrophil niches and T cell exclusion, while regressing lesions showed predominantly lumen-adjacent bacterial localization and spatially organized immune surveillance. These results provide a spatially resolved map of cellular and microbial organisation in early colorectal polyp progression and regression and reveal a microbiome-driven, neutrophil-mediated mechanism of early tumour progression with implications for CRC interception.",
  "abstract_shown": true,
  "affiliations": [
    "Technical University of Munich"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "W. Liang"
    },
    {
      "name": "L. Falk"
    },
    {
      "name": "D. Lucarelli"
    },
    {
      "name": "P. Putze"
    },
    {
      "name": "A. Metwaly"
    },
    {
      "name": "Y. Zheng"
    },
    {
      "name": "F. Springer"
    },
    {
      "name": "T. Winogrodzki"
    },
    {
      "name": "Q. Chan"
    },
    {
      "name": "T. M. Pauli"
    },
    {
      "name": "Y. Zhang"
    },
    {
      "name": "G. Zeller"
    },
    {
      "name": "M. Meier"
    },
    {
      "name": "A. Schnieke"
    },
    {
      "name": "F. Ebner"
    },
    {
      "name": "D. Haller"
    },
    {
      "name": "T. Flisikowska"
    },
    {
      "name": "D. Saur"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Flisikowski"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e2bsqhz0xw8mv.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.07.10.737736",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.07.10.737736v2.full",
  "id": "e2bsqhz0xw8mv",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.07.10.737736v2",
  "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": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|Gut microbiota and health"
    ]
  ],
  "openalex": "W7168149560",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.07.10.737736v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e2bsqhz0xw8mv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:17Z",
      "native_id": "10.64898/2026.07.10.737736",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.07.10.737736v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Microbial Invasion and Immunosuppression Drives Adenoma Progression in Early Colorectal Cancer Development",
  "title_text": "Microbial Invasion and Immunosuppression Drives Adenoma Progression in Early Colorectal Cancer Development",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:17Z",
  "url": "https://research.draconitic.com/paper/e2bsqhz0xw8mv",
  "venue": "bioRxiv",
  "versions": []
}