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

Wirbel, Jakob; Pyl, Paul Theodor LU ; Kartal, Ece; Zych, Konrad; Kashani, Alireza; Milanese, Alessio; Fleck, Jonas S.; Voigt, Anita Y.; Palleja, Albert and Ponnudurai, Ruby, et al. (2019) In Nature Medicine 25(4). p.679-689
Abstract


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... (More)


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.

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Please use this url to cite or link to this publication:
@article{8d3dbce1-5605-4564-a819-63082c4da5a1,
  abstract     = {<p><br>
                                                         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) &lt; 1 × 10                             <br>
                            <sup>−5</sup><br>
                                                         ). 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.                         <br>
                        </p>},
  author       = {Wirbel, Jakob and Pyl, Paul Theodor and Kartal, Ece and Zych, Konrad and Kashani, Alireza and Milanese, Alessio and Fleck, Jonas S. and Voigt, Anita Y. and Palleja, Albert and Ponnudurai, Ruby and Sunagawa, Shinichi and Coelho, Luis Pedro and Schrotz-King, Petra and Vogtmann, Emily and Habermann, Nina and Niméus, Emma and Thomas, Andrew M. and Manghi, Paolo and Gandini, Sara and Serrano, Davide and Mizutani, Sayaka and Shiroma, Hirotsugu and Shiba, Satoshi and Shibata, Tatsuhiro and Yachida, Shinichi and Yamada, Takuji and Waldron, Levi and Naccarati, Alessio and Segata, Nicola and Sinha, Rashmi and Ulrich, Cornelia M. and Brenner, Hermann and Arumugam, Manimozhiyan and Bork, Peer and Zeller, Georg},
  issn         = {1078-8956},
  language     = {eng},
  number       = {4},
  pages        = {679--689},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer},
  url          = {http://dx.doi.org/10.1038/s41591-019-0406-6},
  volume       = {25},
  year         = {2019},
}