Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer

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Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10 −5 ). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.


  • Jakob Wirbel
  • Ece Kartal
  • Konrad Zych
  • Alireza Kashani
  • Alessio Milanese
  • Jonas S. Fleck
  • Anita Y. Voigt
  • Albert Palleja
  • Ruby Ponnudurai
  • Shinichi Sunagawa
  • Luis Pedro Coelho
  • Petra Schrotz-King
  • Emily Vogtmann
  • Nina Habermann
  • Andrew M. Thomas
  • Paolo Manghi
  • Sara Gandini
  • Davide Serrano
  • Sayaka Mizutani
  • Hirotsugu Shiroma
  • Satoshi Shiba
  • Tatsuhiro Shibata
  • Shinichi Yachida
  • Takuji Yamada
  • Levi Waldron
  • Alessio Naccarati
  • Nicola Segata
  • Rashmi Sinha
  • Cornelia M. Ulrich
  • Hermann Brenner
  • Manimozhiyan Arumugam
  • Peer Bork
  • Georg Zeller
Enheter & grupper
Externa organisationer
  • European Molecular Biology Laboratory Heidelberg
  • University of Copenhagen
  • ETH Zürich
  • Fudan University
  • German Cancer Research Centre
  • National Cancer Institute
  • Skåne University Hospital
  • University of Trento
  • University of São Paulo
  • European Institute of Oncology
  • Tokyo Institute of Technology
  • Japan Society for the Promotion of Science
  • National Cancer Center Research Institute, Japan
  • Osaka University
  • Japan Science and Technology Agency (JST)
  • City University of New York
  • Institute of Experimental Medicine, Czech Academy of Science
  • University of Utah
  • University of Southern Denmark
  • Max Delbrück Center for Molecular Medicine (MDC)
  • Julius Maximilian University of Würzburg

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
  • Bioinformatik och systembiologi
Sidor (från-till)679-689
Antal sidor11
TidskriftNature Medicine
Utgåva nummer4
StatusPublished - 2019 apr
Peer review utfördJa