{
  "abstract": "The biological and clinical significance of the intratumoral microbiota in pancreatic ductal adenocarcinoma (PDAC) remains poorly defined. Using oncogenic Kras-driven mouse models of pancreatic tumorigenesis and human pancreatic tissue from patients with non-metastatic PDAC treated with neoadjuvant (n = 62) or adjuvant therapy (n = 101), along with samples from intraductal papillary mucinous neoplasms (IPMN, n = 24), chronic pancreatitis (CP, n = 33), and healthy donors (n = 9), we determined tissue lipopolysaccharide (LPS), 16S rRNA sequencing, high-resolution quantitative multiplex immunofluorescence of autophagy markers (LAMP2, LC3B) and LPS, 16S rRNA fluorescence in situ hybridization (FISH) staining, and TLR4 signaling. In KrasCre mice, we identified significant bacterial accumulation in the pancreas, indicated by elevated LPS, increased FISH signals, enhanced TLR4 signaling, and activation of autophagy. Administration of exogenous LPS further amplified autophagy and TLR4 signaling, supporting a mechanistic link between microbial sensing and autophagy. In human tissue, both adjuvant and neoadjuvant PDAC samples showed significantly increased bacterial alpha- and beta diversity compared with controls, while CP showed a similar enrichment pattern that IPMN lacks; the underlying microbial diversity differs fundamentally across these conditions. Increased LPS levels, along with elevated autophagy markers and abundant FISH-positive bacteria, support the presence of intratumoral bacteria. Across four independent transcriptomic datasets, PDAC samples showed elevated expression of bacteria-associated pathways (including TLR4) and autophagy-related genes. Clinically, higher autophagy-associated LAMP2-LC3B colocalization and increased densities of FISH-positive cells were independently associated with prolonged survival in both adjuvant and neoadjuvant or combined PDAC patients. Collectively, these findings link intratumoral microbial enrichment to increased autophagy-associated signaling and improved patient outcomes, suggesting that microbial signals within the tumor microenvironment were associated with favorable survival.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General, Visceral and Transplantation Surgery, Heidelberg, Germany.",
    "Translational Research Center, University Clinic Heidelberg, Heidelberg, Germany.",
    "Division of Applied Bioinformatics, The German Cancer Research Center (DKFZ), Heidelberg, Germany.",
    "Technical University Munich, Clinic for Surgery, Munich, Germany.",
    "Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.",
    "Institute of Pathology, University Clinic Heidelberg, Heidelberg, Germany.",
    "Department of Medical Oncology, National Center for Tumor Diseases, University Clinic Heidelberg, Heidelberg, Germany.",
    "Department of Infectious Diseases, Medical Microbiology and Hygiene, University Clinic Heidelberg, Heidelberg, Germany.",
    "Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research(DZL), University Clinic Heidelberg, Heidelberg, Germany.",
    "AREA Science Park, 34149, Trieste, Italy.",
    "Gustave Roussy Cancer Campus, ClinicObiome, Villejuif, France. viebba@units.it.",
    "Department of Medical, Surgical, and Health Sciences, University of Trieste, Trieste, Italy. viebba@units.it.",
    "Department of General, Visceral and Transplantation Surgery, Heidelberg, Germany. franco.fortunato@uni-heidelberg.de.",
    "Translational Research Center, University Clinic Heidelberg, Heidelberg, Germany. franco.fortunato@uni-heidelberg.de."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yifan Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Toohina L Gobin"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhenhua Huang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bingwen Miao"
    },
    {
      "affs": [
        2
      ],
      "name": "Roma Kurilov"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Haitao Sun"
    },
    {
      "affs": [
        3
      ],
      "name": "Christine Tjaden"
    },
    {
      "affs": [
        0
      ],
      "name": "Ulrike Heger"
    },
    {
      "affs": [
        4
      ],
      "name": "Thilo Hackert",
      "orcid": "0000-0002-7012-1196"
    },
    {
      "affs": [
        0
      ],
      "name": "Ulf Hinz",
      "orcid": "0000-0001-8227-968X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Michael Schaefer"
    },
    {
      "affs": [
        5
      ],
      "name": "Frank Bergmann"
    },
    {
      "affs": [
        6
      ],
      "name": "Christoph Springfeld"
    },
    {
      "affs": [
        2
      ],
      "name": "Sadaf S Mughal"
    },
    {
      "affs": [
        2
      ],
      "name": "Benedikt Brors",
      "orcid": "0000-0001-5940-3101"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Patrick Schaal"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Bachar Cheaib"
    },
    {
      "affs": [
        9
      ],
      "name": "Danilo Licastro"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Valerio Iebba",
      "orcid": "0000-0002-0716-306X"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "Franco Fortunato",
      "orcid": "0000-0002-6711-5828"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c5crj2hvca8m3.bib",
  "cited_by": 0,
  "doi": "10.1038/s41419-026-09256-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13720179",
  "id": "c5crj2hvca8m3",
  "issns": [
    "2041-4889"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957626",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
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  "openalex": "W7155971672",
  "pdf_url": "https://europepmc.org/articles/PMC13720179?pdf=render",
  "pmcid": "PMC13720179",
  "pmid": "42957626",
  "published": "2026-10-27",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/c5crj2hvca8m3.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:36Z",
      "native_id": "MED:42957626",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957626"
    },
    {
      "first_seen": "2026-11-02T12:24:01Z",
      "native_id": "PMC13720179",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41419-026-09256-1"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "Autophagy and intratumoral bacteria abundance influence the prognosis of patients with pancreatic carcinoma.",
  "title_text": "Autophagy and intratumoral bacteria abundance influence the prognosis of patients with pancreatic carcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:06Z",
  "url": "https://research.draconitic.com/paper/c5crj2hvca8m3",
  "venue": "Cell death & disease",
  "versions": []
}