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

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Item Type:	Article
Title:	Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
Creators Name:	Wirbel, J., Pyl, P.T., Kartal, E., Zych, K., Kashani, A., Milanese, A., Fleck, J.S., Voigt, A.Y., Palleja, A., Ponnudurai, R., Sunagawa, S., Coelho, L.P., Schrotz-King, P., Vogtmann, E., Habermann, N., Niméus, E., Thomas, A.M., 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.M., Brenner, H., Arumugam, M., 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
Volume:	25
Number:	4
Page Range:	679-689
Date:	April 2019
Official Publication:	https://doi.org/10.1038/s41591-019-0406-6
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