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

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

doi:10.1038/s41591-019-0406-6

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

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

188 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Medicine
Vol/bind	25
Udgave nummer	4
Sider (fra-til)	679-689
Antal sider	11
ISSN	1078-8956
DOI	https://doi.org/10.1038/s41591-019-0406-6
Status	Udgivet - 1 apr. 2019

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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., ... Zeller, G. (2019). Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nature Medicine, 25(4), 679-689. https://doi.org/10.1038/s41591-019-0406-6

Wirbel, J, Pyl, PT, Kartal, E, Zych, K, Kashani, A, Milanese, A, Fleck, JS, Voigt, AY, Palleja, A, Ponnudurai, R, Sunagawa, S, Coelho, LP, Schrotz-King, P, Vogtmann, E, Habermann, N, Niméus, E, Thomas, AM, 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, CM, Brenner, H, Arumugam, M, Bork, P & Zeller, G 2019, 'Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer', Nature Medicine, bind 25, nr. 4, s. 679-689. https://doi.org/10.1038/s41591-019-0406-6

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

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. ",

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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 - 2019/4/1

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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.

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DO - 10.1038/s41591-019-0406-6

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SP - 679

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JO - Nature Medicine

JF - Nature Medicine

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ER -

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

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