Cited by 1,373Gut microbiota and healthClostridium difficile and Clostridium perfringens researchColorectal Cancer Treatments and Studies

The DOI matches its Crossref record; 83 of the 85 references it cites were found in a registry or an index.

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

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

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Metadata

Authors
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., Serrano, D., Mizutani, S., Shiroma, H., Shiba, S., Shibata, T., Yachida, S., Yamada, T., Waldron, L., Naccarati, A., Segata, N., Sinha, R., Ulrich, C. M., Brenner, H., Arumugam, M., Bork, P., & Zeller, G.
Affiliations
  • European Molecular Biology Laboratory (DE)
  • University of Copenhagen (DK)
  • ETH Zurich (CH)
  • Shanghai Medical College of Fudan University (CN)
  • National Cancer Institute (US)
  • Lund University (SE)
  • Universidade de São Paulo (BR)
  • University of Trento (IT)
  • European Institute of Oncology (IT)
  • Tokyo Institute of Technology (JP)
  • National Cancer Center Research Institute (JP)
  • Institute of Medical Science, The University of Tokyo (JP)
  • City University of New York (US)
  • Italian institute for Genomic Medicine (IT)
  • University of Utah (US)
  • German Cancer Research Center (DE)
Corresponding author
  • Arumugam, Manimozhiyan
  • Zeller, Georg
Venue
Nature Medicine
Published
2019-04
Volume
25
Issue
4
Pages
679-689
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2927453907
Cited by
1,373
References
85
Citations by year
2026: 214 · 2025: 215 · 2024: 224 · 2023: 189 · 2022: 176 · 2021: 169 · 2020: 143 · 2019: 41
FWCI
11.74
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • Iris (University of Trento) (submittedVersion, other-oa)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
  • The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Funders
  • Deutsches Krebsforschungszentrum
  • Huntsman Cancer Foundation
  • Eidgenössische Technische Hochschule Zürich
  • Novo Nordisk
  • Helmut Horten Stiftung
  • National Institutes of Health
  • Japan Society for the Promotion of Science (16H06279, 18K15800)
  • National Cancer Institute (R01CA189184, R01CA207371, ZIACP010198, P30CA042014, U01CA206110)
  • H2020 European Research Council (669830, 716575)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords
colorectal cancer, gut microbiota, fecal metagenome, microbial signatures, cross-study comparison, protein degradation, carbohydrate degradation, secondary bile acids, cancer diagnosis
MeSH terms
Gastrointestinal Microbiome, Adenoma, Aged, Feces, Female, Humans, Male, Middle Aged, Models, Biological, Species Specificity, Biomarkers, Tumor, Colorectal Neoplasms, Reproducibility of Results, Cohort Studies, Databases, Genetic, Metagenome

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