title: Potential of fecal microbiota for early-stage detection of colorectal cancer.
abstract: Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Zeller
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany Department of Gastroenterology and LIC-EA4393-EC2M3, APHP and UPEC Université Paris-Est Créteil, Créteil, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Tap
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany Department of Applied Tumor Biology, Institute of Pathology University Hospital Heidelberg, Heidelberg, Germany Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Anita Y
authors.initials: AY
authors.lastname: Voigt
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sunagawa
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Jens Roat
authors.initials: JR
authors.lastname: Kultima
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Paul I
authors.initials: PI
authors.lastname: Costea
authors.affiliation: Department of Gastroenterology and LIC-EA4393-EC2M3, APHP and UPEC Université Paris-Est Créteil, Créteil, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Amiot
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Böhm
authors.affiliation: Department of Surgery, APHP and UPEC Université Paris-Est Créteil, Créteil, France.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brunetti
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Habermann
authors.affiliation: Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Rajna
authors.initials: R
authors.lastname: Hercog
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
authors.affiliation: Department of Radiology, APHP and UPEC Université Paris-Est Créteil, Créteil, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Luciani
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Mende
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schneider
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Schrotz-King
authors.affiliation: Department of Medical Oncology, APHP and UPEC Université Paris-Est Créteil, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournigand
authors.affiliation: Department of Pathology and LIC-EA4393-EC2M3, APHP and UPEC Université Paris-Est Créteil, Créteil, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Tran Van Nhieu
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, Tokyo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zimmermann
authors.affiliation: Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology University Hospital Heidelberg, Heidelberg, Germany Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany German Cancer Research Center (DKFZ), Heidelberg, Germany Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, USA.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology University Hospital Heidelberg, Heidelberg, Germany Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.affiliation: Department of Gastroenterology and LIC-EA4393-EC2M3, APHP and UPEC Université Paris-Est Créteil, Créteil, France iradj.sobhani@hmn.aphp.fr bork@embl.de.
authors.forename: Iradj
authors.initials: I
authors.lastname: Sobhani
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany Max Delbrück Centre for Molecular Medicine, Berlin, Germany iradj.sobhani@hmn.aphp.fr bork@embl.de.
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000382:microbiology*; D055088:Early Detection of Cancer / Q000379:methods*; D005243:Feces / Q000382:microbiology*; D006801:Humans; D056186:Metagenomics / Q000379:methods; D064307:Microbiota; D058889:Molecular Typing; D009780:Occult Blood; D012680:Sensitivity and Specificity
keywords: cancer screening; colorectal cancer; fecal biomarkers; human gut microbiome; metagenomics