{
  "abstract": "Background While colorectal cancer (CRC) has been linked to the gut microbiome, it remains unclear whether specific microbial signatures are detectable in precursor lesions such as adenomatous polyps, serrated lesions or sessile serrated lesions.Objective To assess gut microbiome taxonomic and functional associations with colorectal neoplasia presence, severity (non-advanced, advanced and CRC) and subtype and evaluate predictive potential in high-risk neoplasia.Design Analysed cross-sectional stool metagenomes (pre-colonoscopy) from 1762 participants (97% White British) undergoing colonoscopy in the multicentre COLO-COHORT study. Neoplasia was classified per British Society of Gastroenterology surveillance guidelines. Linear mixed-effects models and random forest classifiers assessed taxonomic and functional associations, adjusting for dietary, clinical and lifestyle covariates.Results Gut microbiome composition differences between individuals with and without neoplasia were statistically significant but minimal (R 2=0.0008, p=0.03). A small number of species, including Mediterraneibacter faecis and Pseudoruminococcus massiliensis, and microbial pathways, including amino acid biosynthesis and β-lactam resistance, were modestly linked to neoplasia, particularly early lesions (q value <0.05). Associations were generally weak and attenuated after covariate adjustment. Predictive models combining the microbiome with clinical/demographic features modestly improved high-risk neoplasia classification (area under the curve=0.64 vs 0.58 for clinical/demographic features alone).Conclusion This large prospective cross-sectional study found weak and inconsistent associations between the gut microbiome and premalignant colorectal neoplasia, with no robust microbial signatures. Findings suggest that previously reported microbial shifts may emerge later in disease progression, potentially as a consequence rather than a cause of CRC. Longitudinal, multiomic studies disentangling temporal and causal pathways between the gut microbiome and neoplasia are required.",
  "authors": [
    {
      "affiliations": [
        "Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Panayiotis Louca"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, South Tyneside District Hospital, South Tyneside and Sunderland NHS Foundation Trust, South Shields, UK",
        "Population Health Sciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK"
      ],
      "name": "Sarah Manning"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, South Tyneside District Hospital, South Tyneside and Sunderland NHS Foundation Trust, South Shields, UK",
        "Population Health Sciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK"
      ],
      "name": "Eleanor Hackney"
    },
    {
      "affiliations": [
        "Population Health Sciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK"
      ],
      "name": "Linda Sharp"
    },
    {
      "affiliations": [
        "Leeds Institute of Medical Research, University of Leeds, St James’s University Hospital, Leeds, UK"
      ],
      "name": "Mark A Hull"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, South Tyneside District Hospital, South Tyneside and Sunderland NHS Foundation Trust, South Shields, UK"
      ],
      "name": "Sara Koo"
    },
    {
      "affiliations": [
        "Translational and Clinical Research Institute, Newcastle University, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK"
      ],
      "name": "Gregory R Young"
    },
    {
      "affiliations": [
        "Population Health Sciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK"
      ],
      "name": "Guy S Taylor"
    },
    {
      "affiliations": [
        "Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Yashvee Dunneram"
    },
    {
      "affiliations": [
        "Leeds Institute of Medical Research, University of Leeds, St James’s University Hospital, Leeds, UK"
      ],
      "name": "Suparna Mitra"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, South Tyneside District Hospital, South Tyneside and Sunderland NHS Foundation Trust, South Shields, UK"
      ],
      "name": "James S Hampton"
    },
    {
      "affiliations": [
        "Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle University, Newcastle upon Tyne, UK",
        "Population Health Sciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK"
      ],
      "name": "Christina Dobson"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, South Tyneside District Hospital, South Tyneside and Sunderland NHS Foundation Trust, South Shields, UK",
        "Population Health Sciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK"
      ],
      "name": "Laura J Neilson"
    },
    {
      "affiliations": [
        "North East Hub, Bowel Cancer Screening Programme, Gateshead, UK"
      ],
      "name": "Caroline Addison"
    },
    {
      "affiliations": [
        "Microbiome Research Centre, St George & Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia"
      ],
      "name": "Emad M El-Omar"
    },
    {
      "affiliations": [
        "Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle University, Newcastle upon Tyne, UK",
        "Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, South Tyneside District Hospital, South Tyneside and Sunderland NHS Foundation Trust, South Shields, UK",
        "Population Health Sciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK",
        "Leeds Institute of Medical Research, University of Leeds, St James’s University Hospital, Leeds, UK",
        "Translational and Clinical Research Institute, Newcastle University, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK",
        "North East Hub, Bowel Cancer Screening Programme, Gateshead, UK",
        "Microbiome Research Centre, St George & Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia"
      ],
      "name": "the COLO-COHORT research team"
    },
    {
      "affiliations": [
        "Translational and Clinical Research Institute, Newcastle University, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK"
      ],
      "name": "Christopher J Stewart"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, South Tyneside District Hospital, South Tyneside and Sunderland NHS Foundation Trust, South Shields, UK",
        "Population Health Sciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK"
      ],
      "name": "Colin J Rees"
    }
  ],
  "title": "Gut microbiome signatures in colorectal neoplasia: a cross-sectional study across neoplasia stages and subtypes",
  "uid": "d1cdd8d0-d948-5e0d-8ece-c422dddc0f56"
}