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Potential of fecal microbiota for early-stage detection of colorectal cancer |
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| 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 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. |
| Keywords: | cancer screening colorectal cancer fecal biomarkers human gut microbiome metagenomics |
