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

Georg Zeller(European Molecular Biology Laboratory), Julien Tap(Université Paris-Est Créteil), Anita Y. Voigt(German Cancer Research Center), Shinichi Sunagawa(European Molecular Biology Laboratory), Jens Roat Kultima(European Molecular Biology Laboratory), Paul Igor Costea(European Molecular Biology Laboratory), Aurélien Amiot(Université Paris-Est Créteil), Jürgen Böhm(German Cancer Research Center), Francesco Brunetti(Université Paris-Est Créteil), Nina Habermann(German Cancer Research Center), Rajna Hercog(European Molecular Biology Laboratory), Moritz Koch(Heidelberg University), Alain Luciani(Université Paris-Est Créteil), Daniel R. Mende(European Molecular Biology Laboratory), Martin Schneider(Heidelberg University), Petra Schrotz‐King(German Cancer Research Center), Christophe Tournigand(Université Paris-Est Créteil), Jeanne Tran Van Nhieu(Université Paris-Est Créteil), Takuji Yamada(Tokyo Institute of Technology), Jürgen Zimmermann(European Molecular Biology Laboratory), Vladimı́r Beneš(European Molecular Biology Laboratory), Matthias Kloor(German Cancer Research Center), Cornelia M. Ulrich(Heidelberg University), Magnus von Knebel Doeberitz(German Cancer Research Center), Iradj Sobhani(Université Paris-Est Créteil), Peer Bork(Max Delbrück Center)
Molecular Systems Biology
November 1, 2014
Cited by 1,437Open Access
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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.


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