Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
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Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. / Wirbel, Jakob; Pyl, Paul Theodor; Kartal, Ece; Zych, Konrad; Kashani, Alireza; Milanese, Alessio; Fleck, Jonas S; Voigt, Anita Y; Palleja, Albert; Ponnudurai, Ruby; Sunagawa, Shinichi; Coelho, Luis Pedro; Schrotz-King, Petra; Vogtmann, Emily; Habermann, Nina; Niméus, Emma; Thomas, Andrew M; Manghi, Paolo; Gandini, Sara; Serrano, Davide; Mizutani, Sayaka; Shiroma, Hirotsugu; Shiba, Satoshi; Shibata, Tatsuhiro; Yachida, Shinichi; Yamada, Takuji; Waldron, Levi; Naccarati, Alessio; Segata, Nicola; Sinha, Rashmi; Ulrich, Cornelia M; Brenner, Hermann; Arumugam, Manimozhiyan; Bork, Peer; Zeller, Georg.
In: Nature Medicine, Vol. 25, No. 4, 2019, p. 679-689.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
AU - Wirbel, Jakob
AU - Pyl, Paul Theodor
AU - Kartal, Ece
AU - Zych, Konrad
AU - Kashani, Alireza
AU - Milanese, Alessio
AU - Fleck, Jonas S
AU - Voigt, Anita Y
AU - Palleja, Albert
AU - Ponnudurai, Ruby
AU - Sunagawa, Shinichi
AU - Coelho, Luis Pedro
AU - Schrotz-King, Petra
AU - Vogtmann, Emily
AU - Habermann, Nina
AU - Niméus, Emma
AU - Thomas, Andrew M
AU - Manghi, Paolo
AU - Gandini, Sara
AU - Serrano, Davide
AU - Mizutani, Sayaka
AU - Shiroma, Hirotsugu
AU - Shiba, Satoshi
AU - Shibata, Tatsuhiro
AU - Yachida, Shinichi
AU - Yamada, Takuji
AU - Waldron, Levi
AU - Naccarati, Alessio
AU - Segata, Nicola
AU - Sinha, Rashmi
AU - Ulrich, Cornelia M
AU - Brenner, Hermann
AU - Arumugam, Manimozhiyan
AU - Bork, Peer
AU - Zeller, Georg
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1038/s41591-019-0406-6
DO - 10.1038/s41591-019-0406-6
M3 - Journal article
C2 - 30936547
VL - 25
SP - 679
EP - 689
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 4
ER -
ID: 216516357