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

Study information

Reviewed Marked as Reviewed by Lwaldron on 2021/06/26

study design

meta-analysis
case-control

Citation

PMID PubMed identifier for scientific articles.

30936547

DOI Digital object identifier for electronic documents.

10.1038/s41591-019-0406-6

URI

Authors

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

Journal

Nature medicine

Year

2019

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.

Experiment 1

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Reviewed Marked as Reviewed by Lwaldron on 2021/06/26

Curated date: 2021/06/26

Curator: Lwaldron

Revision editor(s): Lwaldron, WikiWorks, Peace Sandy

Subjects

Location of subjects: Austria; China; France; Germany; Italy; Japan; United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Colorectal cancer cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine,Colorectal cancer

Group 0 name Corresponds to the control (unexposed) group for case-control studies: controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: colorectal cancer

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Colorectal cancer cases from eight independent studies

Group 0 sample size Number of subjects in the control (unexposed) group: 392

Group 1 sample size Number of subjects in the case (exposed) group: 386

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Signature 1

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Curated date: 2021/06/26

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Source: Fig. 1 (species) and extended data fig. 4 (genera)

Description: Species and genera enriched in CRC vs controls

Abundance in Group 1: increased abundance in colorectal cancer

NCBI	Quality Control	Links
Anaerococcus
Anaerococcus obesiensis
Anaerotruncus sp.
Clostridiales bacterium
Dialister sp.
Enterocloster bolteae
Eubacterium
Fusobacterium
Fusobacterium nucleatum
Fusobacterium animalis
Fusobacterium vincentii
Fusobacterium sp.
Gemella
Gemella morbillorum
Hungatella
Hungatella hathewayi
Lachnoclostridium
Leptotrichia
Parvimonas
Parvimonas micra
Parvimonas sp.
Peptostreptococcaceae bacterium
Peptostreptococcus
Peptostreptococcus stomatis
Porphyromonas
Porphyromonas asaccharolytica
Porphyromonas somerae
Porphyromonas uenonis
Prevotella intermedia
Prevotella nigrescens
Solobacterium
Solobacterium moorei
Subdoligranulum
Subdoligranulum sp.
[Clostridium] symbiosum
[Ruminococcus] torques

Revision editor(s): Lwaldron

Signature 2

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Curated date: 2021/07/05

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Source: Extended Data Fig. 4

Description: Genera enriched in CRC vs controls

Abundance in Group 1: increased abundance in colorectal cancer

NCBI	Quality Control	Links
Anaerococcus
Eubacterium
Fusobacterium
Gemella
Hungatella
Lachnoclostridium
Leptotrichia
Parvimonas
Peptostreptococcus
Porphyromonas
Solobacterium
Subdoligranulum

Revision editor(s): Lwaldron

Signature 3

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Curated date: 2021/07/05

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Source: Fig. 1

Description: Species enriched in CRC vs controls

Abundance in Group 1: increased abundance in colorectal cancer

NCBI	Quality Control	Links
Anaerococcus obesiensis
Anaerotruncus sp.
Dialister sp.
Enterocloster bolteae
Fusobacterium nucleatum
Fusobacterium animalis
Fusobacterium vincentii
Fusobacterium sp.
Gemella morbillorum
Hungatella hathewayi
Parvimonas micra
Parvimonas sp.
Peptostreptococcus stomatis
Porphyromonas asaccharolytica
Porphyromonas somerae
Porphyromonas uenonis
Prevotella intermedia
Prevotella nigrescens
Solobacterium moorei
Subdoligranulum sp.
[Clostridium] symbiosum
[Ruminococcus] torques
Clostridiales bacterium
Peptostreptococcaceae bacterium

Revision editor(s): Lwaldron