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Nat Med. 2019 Apr;25(4):679-689. doi: 10.1038/s41591-019-0406-6. Epub 2019 Apr 1.

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

Author information

1
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
2
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine, University of Copenhagen, Copenhagen, Denmark.
3
Division of Surgery, Oncology and Pathology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
4
Molecular Medicine Partnership Unit, Heidelberg, Germany.
5
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
6
Department of Biology, ETH Zürich, Zürich, Switzerland.
7
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
8
Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
9
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
10
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
11
Division of Surgery, Department of Clinical Sciences Lund, Faculty of Medicine, Skane University Hospital, Lund, Sweden.
12
Department CIBIO, University of Trento, Trento, Italy.
13
Biochemistry Department, Chemistry Institute, University of São Paulo, São Paulo, Brazil.
14
IEO, European Institute of Oncology IRCCS, Milan, Italy.
15
School of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan.
16
Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
17
Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
18
Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
19
Department of Cancer Genome Informatics, Graduate School of Medicine/Faculty of Medicine, Osaka University, Osaka, Japan.
20
PRESTO, Japan Science and Technology Agency, Saitama, Japan.
21
Graduate School of Public Health and Health Policy, City University of New York, New York, NY, USA.
22
Institute for Implementation Science in Population Health, City University of New York, New York, NY, USA.
23
Italian Institute for Genomic Medicine, Turin, Italy.
24
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Prague, Czech Republic.
25
Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
26
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
27
German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
28
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine, University of Copenhagen, Copenhagen, Denmark. arumugam@sund.ku.dk.
29
Faculty of Healthy Sciences, University of Southern Denmark, Odense, Denmark. arumugam@sund.ku.dk.
30
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. bork@embl.de.
31
Molecular Medicine Partnership Unit, Heidelberg, Germany. bork@embl.de.
32
Max Delbrück Centre for Molecular Medicine, Berlin, Germany. bork@embl.de.
33
Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany. bork@embl.de.
34
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. zeller@embl.de.

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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PMID:
30936547
DOI:
10.1038/s41591-019-0406-6
[Indexed for MEDLINE]

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