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

Item Type:Article
Title:Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
Creators Name:Wirbel, J. and Pyl, P.T. and Kartal, E. and Zych, K. and Kashani, A. and Milanese, A. and Fleck, J.S. and Voigt, A.Y. and Palleja, A. and Ponnudurai, R. and Sunagawa, S. and Coelho, L.P. and Schrotz-King, P. and Vogtmann, E. and Habermann, N. and Niméus, E. and Thomas, A.M. and Manghi, P. and Gandini, S. and Serrano, D. and Mizutani, S. and Shiroma, H. and Shiba, S. and Shibata, T. and Yachida, S. and Yamada, T. and Waldron, L. and Naccarati, A. and Segata, N. and Sinha, R. and Ulrich, C.M. and Brenner, H. and Arumugam, M. and Bork, P. and Zeller, G.
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 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.
Keywords:Adenoma, Biological Models, Cohort Studies, Colorectal Neoplasms, Genetic Databases, Feces, Gastrointestinal Microbiome, Metagenome, Reproducibility of Results, Species Specificity, Tumor Biomarkers
Source:Nature Medicine
ISSN:1078-8956
Publisher:Nature Publishing Group (U.S.A.)
Volume:25
Number:4
Page Range:679-689
Date:April 2019
Official Publication:https://doi.org/10.1038/s41591-019-0406-6
PubMed:View item in PubMed

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