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 & 15 andre 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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftNature Medicine
Vol/bind25
Udgave nummer4
Sider (fra-til)679-689
ISSN1078-8956
DOI
StatusUdgivet - apr. 2019

Fingeraftryk

Metagenome
Meta-Analysis
Colorectal Neoplasms
Genes
Microbiota
Functional analysis
Meats
Mucins
Nutrition
Bile Acids and Salts
Metagenomics
Fats
Carbohydrates
Firearms
Degradation
Meat
Diet
Proteins
Neoplasms

Citer dette

Wirbel, J., Pyl, P. T., Kartal, E., Zych, K., Kashani, A., Milanese, A., ... 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, 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. / Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. I: Nature Medicine. 2019 ; Bind 25, Nr. 4. s. 679-689.
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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.",
keywords = "Adenoma/genetics, Aged, Biomarkers, Tumor/metabolism, Cohort Studies, Colorectal Neoplasms/genetics, Databases, Genetic, Feces/microbiology, Female, Gastrointestinal Microbiome/genetics, Humans, Male, Metagenome, Middle Aged, Models, Biological, Reproducibility of Results, Species Specificity",
author = "Jakob Wirbel and Pyl, {Paul Theodor} and Ece Kartal and Konrad Zych and Alireza Kashani and Alessio Milanese and Fleck, {Jonas S} and Voigt, {Anita Y} and Albert Palleja and Ruby Ponnudurai and Shinichi Sunagawa and Coelho, {Luis Pedro} and Petra Schrotz-King and Emily Vogtmann and Nina Habermann and Emma Nim{\'e}us and Thomas, {Andrew M} and Paolo Manghi and Sara Gandini and Davide Serrano and Sayaka Mizutani and Hirotsugu Shiroma and Satoshi Shiba and Tatsuhiro Shibata and Shinichi Yachida and Takuji Yamada and Levi Waldron and Alessio Naccarati and Nicola Segata and Rashmi Sinha and Ulrich, {Cornelia M} and Hermann Brenner and Manimozhiyan Arumugam and Peer Bork and Georg Zeller",
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month = "4",
doi = "10.1038/s41591-019-0406-6",
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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

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.

I: Nature Medicine, Bind 25, Nr. 4, 04.2019, s. 679-689.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - 2019/4

Y1 - 2019/4

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.

KW - Adenoma/genetics

KW - Aged

KW - Biomarkers, Tumor/metabolism

KW - Cohort Studies

KW - Colorectal Neoplasms/genetics

KW - Databases, Genetic

KW - Feces/microbiology

KW - Female

KW - Gastrointestinal Microbiome/genetics

KW - Humans

KW - Male

KW - Metagenome

KW - Middle Aged

KW - Models, Biological

KW - Reproducibility of Results

KW - Species Specificity

U2 - 10.1038/s41591-019-0406-6

DO - 10.1038/s41591-019-0406-6

M3 - Journal article

VL - 25

SP - 679

EP - 689

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 4

ER -