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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Jakob Wirbel
  • Paul Theodor Pyl
  • 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
  • Emma Niméus
  • 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
  • Peer Bork
  • Georg Zeller

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.

Original languageEnglish
JournalNature Medicine
Issue number4
Pages (from-to)679-689
Number of pages11
Publication statusPublished - 2019

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