{
  "abstract": "Background Western diet and associated production of secondary bile acids (BAs) have been linked to the development of sporadic colorectal cancer (CRC). Despite observational studies showing that secondary BAs produced by 7α-dehydroxylating (7αDH+) gut bacteria are increased in CRC, a causal proof of their tumour-promoting effects is lacking.Objective Investigate the causal role of BAs produced by 7αDH+ gut bacteria in CRC.Design We performed feeding studies in a porcine model of CRC combined with multi-omics analyses and gnotobiotic mouse models colonised with 7αDH+ bacteria or a genetically modified strain to demonstrate causality.Results Western diet exacerbated the CRC phenotype in APC 1311/+ pigs. This was accompanied by increased levels of the secondary BA deoxycholic acid (DCA) and higher colonic epithelial cell proliferation. The latter was counteracted by the BA-scavenging drug colestyramine. Metagenomic analysis across multiple human cohorts revealed higher occurrence of bai (BA inducible) operons from Clostridium scindens and close relatives in faeces of patients with CRC. Addition of these specific 7αDH+ bacteria (C. scindens/Extibacter muris) to defined communities of gut bacteria led to DCA production and increased colon tumour burden in mouse models of chemically or genetically induced CRC. A mutant strain of Faecalicatena contorta lacking 7αDH caused fewer colonic tumours in azoxymethane/dextran sodium sulfate treated mice and triggered less epithelial cell proliferation in human colon organoids compared with wild-type F. contorta.Conclusion This work provides functional evidence for the causal role of secondary BAs produced by gut bacteria through 7αDH in CRC under adverse dietary conditions, opening avenues for future preventive strategies.",
  "authors": [
    {
      "affiliations": [
        "Research Group WESTGUT, ZIEL - Institute for Food & Health, Technical University of Munich, Freising, Germany",
        "Gnotobiology Research Unit, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany"
      ],
      "name": "Annika Osswald"
    },
    {
      "affiliations": [
        "Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany"
      ],
      "name": "Esther Wortmann"
    },
    {
      "affiliations": [
        "Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany"
      ],
      "name": "David Wylensek"
    },
    {
      "affiliations": [
        "Chair of Nutrition and Immunology, School of Life Sciences, Technical University of Munich, Freising, Germany"
      ],
      "name": "Stephanie Kuhls"
    },
    {
      "affiliations": [
        "Chair of Nutrition and Immunology, School of Life Sciences, Technical University of Munich, Freising, Germany"
      ],
      "name": "Olivia I Coleman"
    },
    {
      "affiliations": [
        "Department of Internal Medicine A, University Medicine Greifswald, Greifswald, Germany"
      ],
      "name": "Kenneth Peuker"
    },
    {
      "affiliations": [
        "Department of Internal Medicine A, University Medicine Greifswald, Greifswald, Germany"
      ],
      "name": "Anne Strigli"
    },
    {
      "affiliations": [
        "Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany"
      ],
      "name": "Quinten R Ducarmon"
    },
    {
      "affiliations": [
        "Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany",
        "Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Martin Larralde"
    },
    {
      "affiliations": [
        "Chair of Livestock Biotechnology, School of Life Sciences, Technical University of Munich, Freising, Germany",
        "Chair of Infections Pathogenesis, School of Life Sciences, Technical University of Munich, Freising, Germany"
      ],
      "name": "Wei Liang"
    },
    {
      "affiliations": [
        "Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany"
      ],
      "name": "Nicole S Treichel"
    },
    {
      "affiliations": [
        "Institute of Pharmacy, Department of Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany"
      ],
      "name": "Fabian Schumacher"
    },
    {
      "affiliations": [
        "Environmental Microbiology Laboratory, School of Architecture, Civil and Environmental Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland"
      ],
      "name": "Colin Volet"
    },
    {
      "affiliations": [
        "Institute of Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, Regensburg, Germany"
      ],
      "name": "Silke Matysik"
    },
    {
      "affiliations": [
        "Bavarian Center for Biomolecular Mass Spectrometry, School of Life Sciences, Technical University of Munich, Freising, Germany"
      ],
      "name": "Karin Kleigrewe"
    },
    {
      "affiliations": [
        "Bavarian Center for Biomolecular Mass Spectrometry, School of Life Sciences, Technical University of Munich, Freising, Germany"
      ],
      "name": "Michael Gigl"
    },
    {
      "affiliations": [
        "Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Berlin, Germany"
      ],
      "name": "Sascha Rohn"
    },
    {
      "affiliations": [
        "The Jill Roberts Institute for Research in IBD, Department of Medicine, Weill Cornell Medicine, New York, New York, USA"
      ],
      "name": "Chun-Jun Guo"
    },
    {
      "affiliations": [
        "Institute of Pharmacy, Department of Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany"
      ],
      "name": "Burkhard Kleuser"
    },
    {
      "affiliations": [
        "Institute of Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, Regensburg, Germany"
      ],
      "name": "Gerhard Liebisch"
    },
    {
      "affiliations": [
        "Chair of Livestock Biotechnology, School of Life Sciences, Technical University of Munich, Freising, Germany"
      ],
      "name": "Angelika Schnieke"
    },
    {
      "affiliations": [
        "Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, USA"
      ],
      "name": "Jason M Ridlon"
    },
    {
      "affiliations": [
        "Environmental Microbiology Laboratory, School of Architecture, Civil and Environmental Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland"
      ],
      "name": "Rizlan Bernier-Latmani"
    },
    {
      "affiliations": [
        "Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany",
        "Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Georg Zeller"
    },
    {
      "affiliations": [
        "Department of Internal Medicine A, University Medicine Greifswald, Greifswald, Germany",
        "Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland"
      ],
      "name": "Sebastian Zeissig"
    },
    {
      "affiliations": [
        "Chair of Nutrition and Immunology, School of Life Sciences, Technical University of Munich, Freising, Germany",
        "ZIEL – Institute for Food & Health, Technical University of Munich, Freising, Germany"
      ],
      "name": "Dirk Haller"
    },
    {
      "affiliations": [
        "Chair of Livestock Biotechnology, School of Life Sciences, Technical University of Munich, Freising, Germany",
        "Chair of Infections Pathogenesis, School of Life Sciences, Technical University of Munich, Freising, Germany"
      ],
      "name": "Krzysztof Flisikowski"
    },
    {
      "affiliations": [
        "Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany"
      ],
      "name": "Thomas Clavel"
    },
    {
      "affiliations": [
        "Research Group WESTGUT, ZIEL - Institute for Food & Health, Technical University of Munich, Freising, Germany",
        "Gnotobiology Research Unit, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany"
      ],
      "name": "Soeren Ocvirk"
    }
  ],
  "title": "Secondary bile acid production by gut bacteria promotes Western diet-associated colorectal cancer",
  "uid": "e3f6b081-f8dd-57b4-9905-29efe06e7aff"
}