Journal Article

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

Schrotz-King, Petra, Vogtmann Emily, Naccarati Alessio, Coelho, Luis Pedro, Manghi Paolo, Fleck, Jonas S, Zeller, Georg, Wirbel Jakob, Segata Nicola, Milanese Alessio, Habermann, Nina, Sinha Rashmi, Arumugam Manimozhiyan, Gandini, Sara, Yachida Shinichi, Sunagawa Shinichi, Mizutani Sayaka, Zych Konrad, Kashani Alireza, Shibata Tatsuhiro, Pyl Paul Theodor, Brenner, Hermann, Waldron Levi, Shiroma Hirotsugu, Palleja Albert, Thomas, Andrew M, Bork Peer, Ponnudurai Ruby, Kartal Ece, Serrano, Davide, Shiba Satoshi, Niméus Emma, Voigt, Anita Y, Yamada Takuji, Ulrich, Cornelia M

2019

Overview

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.Cross-study analysis defines fecal microbial species associated with colorectal cancer.

• Publisher: Nature Publishing Group
• Subject: Bile acids / Cancer / Carbohydrates / Catabolism / Colorectal cancer / Colorectal carcinoma / Fecal microflora / Functional analysis / Genes / Intestinal microflora / Meat / Meta-analysis / Microbiomes / Microorganisms / Mucin / Proteins / Shotguns / Signatures