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Potential of fecal microbiota for early-stage detection of colorectal cancer
Authors:Shinichi Sunagawa  Jens Roat Kultima  Paul I Costea  Aurélien Amiot  Jürgen Böhm  Francesco Brunetti  Nina Habermann  Rajna Hercog  Moritz Koch  Alain Luciani  Daniel R Mende  Martin A Schneider  Petra Schrotz‐King  Christophe Tournigand  Jeanne Tran Van Nhieu  Takuji Yamada  Jürgen Zimmermann  Vladimir Benes  Matthias Kloor  Cornelia M Ulrich  Magnus von Knebel Doeberitz  Iradj Sobhani  Peer Bork
Affiliation:1. Structural and Computational Biology Unit, European Molecular Biology Laboratory, , Heidelberg, Germany;2. Department of Gastroenterology and LIC‐EA4393‐EC2M3, APHP and UPEC Université Paris‐Est Créteil, , Créteil, France;3. Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, , Heidelberg, Germany;4. German Cancer Research Center (DKFZ), , Heidelberg, Germany;5. Department of Surgery, APHP and UPEC Université Paris‐Est Créteil, , Créteil, France;6. Genomics Core Facility, European Molecular Biology Laboratory, , Heidelberg, Germany;7. Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, , Heidelberg, Germany;8. Department of Radiology, APHP and UPEC Université Paris‐Est Créteil, , Créteil, France;9. Department of Medical Oncology, APHP and UPEC Université Paris‐Est Créteil, , Créteil, France;10. Department of Pathology and LIC‐EA4393‐EC2M3, APHP and UPEC Université Paris‐Est Créteil, , Créteil, France;11. Department of Biological Information, Tokyo Institute of Technology, , Tokyo, Japan;12. Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, , Heidelberg, Germany;13. Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), , Heidelberg, Germany;14. Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg and European Molecular Biology Laboratory, , Heidelberg, Germany;15. Fred Hutchinson Cancer Research Center (FHCRC), , Seattle, WA, USA;16. Max Delbrück Centre for Molecular Medicine, , Berlin, Germany
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 beexplored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers thatdistinguished 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) andwhen both approaches were combined, sensitivity improved > 45% relative to the FOBT,while maintaining its specificity. Accuracy of metagenomic CRC detection did not differsignificantly between early- and late-stage cancer and could be validated in independent patient andcontrol populations (N = 335) from different countries. CRC-associatedchanges in the fecal microbiome at least partially reflected microbial community composition at thetumor itself, indicating that observed gene pool differences may reveal tumor-relatedhost–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation incontrols to utilization of host carbohydrates and amino acids in CRC patients, accompanied by anincrease of lipopolysaccharide metabolism.
Keywords:cancer screening   colorectal cancer   fecal biomarkers   human gut microbiome   metagenomics
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