{
  "abstract": "Background: Growing evidence links the gut microbiome to colorectal cancer (CRC) progression, with certain bacterial species enriched in specific molecular tumor subtypes. DNA mismatch repair deficiency in CRC, evidenced by the presence of microsatellite instability (MSI), has been consistently associated with a favorable prognosis, and may be related to certain aspects of the microbiome. Here, we examined the relationship between tumor microbial biodiversity and MSI status. Methods: Diagnostic tumor tissue samples were obtained from the Seattle site of the Colon Cancer Family Registry (SCCFR) and a companion study; both recruited patients diagnosed with incident CRC from 1998 to 2007. MSI status assessment and prokaryotic 16S rRNA gene sequencing was performed on the tumor tissue samples. We used an adaptive test of alpha-diversity (aMiAD) to estimate the association between microbial biodiversity and MSI status. We performed differential abundance analysis with ANCOM-BC to identify enriched genera in tumor tissue, based on dichotomized MSI status. Analyses were adjusted for age, sex, smoking history, and tumor location (N = 632). Results: The adaptive aMiAD effect estimate was −1.08 (p = 0.29), suggesting that MSI-high tumors had lower estimated alpha-diversity, though this difference was not statistically significant. We identified 20 differentially abundant genera in CRC tumors according to MSI status, with 8 enriched genera and 12 depleted genera in MSI-high tumors. The most strongly enriched genera in MSI-high tumors were Gemella and Lawsonella, while Sporolactobacillaceae and Cloacibacterium were the most strongly depleted. Fusobacterium was enriched in MSI-high tumors only after subsetting the genus to Fusobacterium nucleatum specific sequences. Conclusions: We did not detect a statistically significant association between the adaptive alpha-diversity measure and MSI status, though individual measures concordantly estimated a depletion of alpha-diversity in the MSI-high tumors. We found evidence of differential abundance of certain genera dependent on MSI status, including several novel associations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, United States of America",
    "Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America",
    "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America",
    "Centre for Public Health Research, Massey University, Wellington, New Zealand",
    "Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America",
    "Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America",
    "Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Calen Mendall"
    },
    {
      "affs": [
        1
      ],
      "name": "Meredith A. J. Hullar"
    },
    {
      "affs": [
        2
      ],
      "name": "Keith R. Curtis"
    },
    {
      "affs": [
        3
      ],
      "name": "Courtney M. Hill"
    },
    {
      "affs": [
        4
      ],
      "name": "Claire E. Thomas"
    },
    {
      "affs": [
        5
      ],
      "name": "Ningxin Ma"
    },
    {
      "affs": [
        6
      ],
      "name": "Timothy W. Randolph"
    },
    {
      "name": "Rachel C. Malen"
    },
    {
      "name": "Adriana M. Reedy"
    },
    {
      "name": "Scott LaBrie"
    },
    {
      "name": "John D. Potter"
    },
    {
      "name": "Shuji Ogino"
    },
    {
      "name": "Polly A. Newcomb"
    },
    {
      "name": "Amanda I. Phipps"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1a698m9t4hejh.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0359555",
  "fulltext_url": null,
  "id": "1a698m9t4hejh",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0359555",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Gut microbiota and health"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Ribosomal RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Ribosomes/Ribosomal RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Ribosomes/Ribosomal RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Ecology/Ecological metrics/Species diversity/Shannon index"
    ],
    [
      "plos",
      "/Biology and life sciences/Evolutionary biology/Evolutionary systematics/Phylogenetics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Microbial genomics/Microbiome"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Fusobacteria"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbiome"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Microbial genomics/Microbiome"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Gut bacteria/Fusobacteria"
    ],
    [
      "plos",
      "/Biology and life sciences/Taxonomy/Evolutionary systematics/Phylogenetics"
    ],
    [
      "plos",
      "/Computer and information sciences/Data management/Taxonomy/Evolutionary systematics/Phylogenetics"
    ],
    [
      "plos",
      "/Ecology and environmental sciences/Ecology/Ecological metrics/Species diversity/Shannon index"
    ],
    [
      "plos",
      "/Medicine and health sciences/Diagnostic medicine/Cancer detection and diagnosis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancer detection and diagnosis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Colorectal cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Fusobacteria"
    ]
  ],
  "openalex": "W7126845548",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0359555&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/1a698m9t4hejh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pone.0359555",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0359555"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:ecology",
      "subfield": "ecology"
    },
    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
    },
    {
      "field": "medicine",
      "origin": "plos:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Tumor microbial biodiversity and microsatellite instability in colorectal cancer",
  "title_text": "Tumor microbial biodiversity and microsatellite instability in colorectal cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/1a698m9t4hejh",
  "venue": "PLOS One",
  "versions": []
}