Potential of fecal microbiota for early‐stage detection of colorectal cancer

Molecular Systems Biology

Georg Zeller⁶  Julien Tap⁶  Anita Y Voigt⁶  Shinichi Sunagawa⁶  Jens Roat Kultima⁶  Paul I Costea⁶  Aurélien Amiot¹¹  Jürgen Böhm¹  Francesco Brunetti⁴  Nina Habermann¹  Rajna Hercog²  Moritz Koch⁸  Alain Luciani⁷  Daniel R Mende⁶  Martin A Schneider⁸  Petra Schrotz-King¹  Christophe Tournigand³  Jeanne Tran Van Nhieu⁵  Takuji Yamada^6,9  Jürgen Zimmermann²  Vladimir Benes²  Matthias Kloor^6,10  Cornelia M Ulrich¹  Magnus von Knebel Doeberitz^6,10  Iradj Sobhani¹¹ 

[1] Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany;Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany;Department of Medical Oncology, APHP and UPEC Université Paris-Est Créteil, Créteil, France;Department of Surgery, APHP and UPEC Université Paris-Est Créteil, Créteil, France;Department of Pathology and LIC-EA4393-EC2M3, APHP and UPEC Université Paris-Est Créteil, Créteil, France;Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany;Department of Radiology, APHP and UPEC Université Paris-Est Créteil, Créteil, France;Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany;Department of Biological Information, Tokyo Institute of Technology, Tokyo, Japan;Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany;Department of Gastroenterology and LIC-EA4393-EC2M3, APHP and UPEC Université Paris-Est Créteil, Créteil, France

关键词: cancer screening;    colorectal cancer;    fecal biomarkers;    human gut microbiome;    metagenomics;   

DOI  :  10.15252/msb.20145645

来源: Wiley

【 摘 要 】

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.

Synopsis

Metagenomic profiling of fecal samples from colorectal cancer (CRC) patients in comparison with tumor-free controls reveals strong associations between the gut microbiota and cancer. Their potential for noninvasive cancer screening is explored systematically.

• A classification model based on gut microbial marker species distinguishes CRC patients from controls with similar accuracy as the fecal occult blood test (FOBT), routinely used for clinical screening.
• Combining metagenomic data with the FOBT leads to a relative improvement in sensitivity of > 45% over the FOBT alone at identical specificity.
• Detection accuracy of the metagenomic test is maintained in an independent study population and is still high for alternative microbiome readouts, such as the abundance of 16S rRNA OTUs or families of functionally related genes.
• Functional metagenomic analysis indicates an increased potential of CRC-associated microbiota for degradation of host glycans and amino acids and for pro-inflammatory lipopolysaccharide metabolism.

【 授权许可】

CC BY   
© 2014 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.