Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer.
Document Type
Article
Publication Date
4-1-2019
Publication Title
Nature medicine
Keywords
JGM, Adenoma, Aged, Biomarkers, Tumor, Cohort Studies, Colorectal Neoplasms, Databases, Genetic, Feces, Female, Gastrointestinal Microbiome, Humans, Male, Metagenome, Middle Aged, Models, Biological, Reproducibility of Results, Species Specificity
JAX Source
Nat Med . 2019 Apr;25(4):679-689
Volume
25
Issue
4
First Page
679
Last Page
689
ISSN
1546-170X
PMID
30936547
DOI
10.1038/s41591-019-0406-6
Grant
We are thankful to members of the Zeller, Bork, and Arumugam groups for inspiring discussions. Additionally, we thank Y. P. Yuan and the EMBL Information Technology Core Facility for support with high-performance computing, and the EMBL Genomics Core Facility for their sequencing support. We are also grateful for the advice provided by B. Klaus, EMBL Centre for Statistical Data Analysis. We acknowledge funding from EMBL, the German Cancer Research Center, the Huntsman Cancer Foundation, the Intramural Research Program of the National Cancer Institute, ETH Zürich, and the following external sources: the European Research Council (CancerBiome grant no. ERC-2010-AdG_20100317 to P.B., Microbios grant no. ERC-AdG-669830 to P.B., and Meta-PG grant no. ERC-2016-STG-716575 to N.S.); the Novo Nordisk Foundation (grant no. NNF10CC1016515 to M.A.); the Danish Diabetes Academy supported by the Novo Nordisk Foundation and TARGET Research Initiative (Danish Strategic Research Council grant no. 0603-00484B to M.A.); the Matthias-Lackas Foundation (to C.M.U.); the National Cancer Institute (grant nos. R01 CA189184, R01 CA207371, U01 CA206110, and P30 CA042014 to C.M.U.); the Federal Ministry of Education and Research (BMBF; the de.NBI network no. 031A537B to P.B. and the ERA-NET TRANSCAN project no. 01KT1503 to C.M.U.); the Helmut Horten Foundation (to S.Sunagawa); and the Fundação de Amparo à Pesquisa do Estado de São Paulo (grant no. 16/23527-2 to A.M.T.). For the Italy validation cohorts, funding was provided by the Lega Italiana per La Lotta contro i Tumori. For the Japan validation cohort, funding was provided to T.Y. and S.Y. by the National Cancer Center Research and Development Fund (grant nos. 25-A-4,28-A-4, and 29-A-6); Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development (grant no. JP18ek0109187); Japan Science and Technology Agency-PRESTO (grant no. JPMJPR1507); Japan Society for the Promotion of Science KAKENHI (grant nos. 16J10135, 142558, and 221S0002); Joint Research Project of the Institute of Medical Science, University of Tokyo; and the Takeda Science and Suzuken Memorial Foundations.
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
Recommended Citation
Wirbel J,
Pyl P,
Kartal E,
Zych K,
Kashani A,
Milanese A,
Fleck J,
Voigt A,
Palleja A,
Ponnudurai R,
Sunagawa S,
Coelho L,
Schrotz-King P,
Vogtmann E,
Habermann N,
Niméus E,
Thomas A,
Manghi P,
Gandini S,
Serrano D,
Mizutani S,
Shiroma H,
Shiba S,
Shibata T,
Yachida S,
Yamada T,
Waldron L,
Naccarati A,
Segata N,
Sinha R,
Ulrich C,
Brenner H,
Arumugam M,
Bork P,
Zeller G.
Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med . 2019 Apr;25(4):679-689