The DOI matches its Crossref record; 31 of the 32 references it cites were found in a registry or an index.
Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing
Open accessAbstract
Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect associations that are reproducible and significant after correction for multiple testing.
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“In contrast to 16S rRNA sequencing, whole-genome shotgun metagenomic sequencing provides more comprehensive taxonomic and functional characterization, encompassing broader genomic content and enabling higher-resolution bacterial community profiling.”
From Microbiome meets immunotherapy: unlocking the hidden predictors of immune checkpoint inhibitors (2025) · cites this paper as [147]
Experimental — accuracy not yet measuredIn the citing paper
“Besides Fusobacterium, other oral bacteria and markers of periodontal disease are enriched in colorectal tumors and feces of patients, including the genera of Porphyromonas and Peptostreptococcus, and Parvimonas micra.15, 35, 37, 38, 53”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [37]
In the citing paper
“studies of fecal microbiomes that used either 16s rRNA or shotgun metagenomic sequencing found that F nucleatum to be increased in fecal samples from patients with CRC or adenoma compared with controls (Table 1).15, 18, 35–39”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [37]
In the citing paper
“several studies have shown that compared with controls, patients with CRC had lower abundances of Bifidobacterium and Lactobacillus spp,16, 18 and other SCFA-producing bacteria, such as the genera Clostridium and Roseburia, the family Lachnospiraceae, and Faecalibacterium prausnitzii.15, 35, 37, 45, 53, 129”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [37]
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Self-citationGut metagenome in European women with normal, impaired and diabetic glucose control
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Role of the gut microbiota in nutrition and health
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Metadata
- Authors
- Vogtmann, E., Hua, X., Zeller, G., Sunagawa, S., Voigt, A. Y., Hercog, R., Goedert, J. J., Shi, J., Bork, P., & Sinha, R.
- Affiliations
- National Cancer Institute (US)
- European Molecular Biology Laboratory (DE)
- German Cancer Research Center (DE)
- Corresponding author
- Vogtmann, Emily
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-05-12
- Volume
- 11
- Issue
- 5
- Pages
- e0155362
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4865240
- OpenAlex
- W2377027462
- Cited by
- 366
- References
- 32
- Citations by year
- 2026: 32 · 2025: 42 · 2024: 46 · 2023: 34 · 2022: 44 · 2021: 44 · 2020: 53 · 2019: 25 · 2018: 20 · 2017: 23 · 2016: 3
- FWCI
- 12.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/publicdomain/zero/1.0/ (vor)
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, public-domain)
- Funders
- National Cancer Institute (Intramural Research Program)
- European Research Council (268985)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Keywords
- colorectal cancer, gut microbiota, metagenomics, 16S rRNA, whole genome shotgun sequencing, reproducibility, Fusobacterium, Porphyromonas, Clostridia, fecal microbiota, cross-population comparison
- MeSH terms
- Gastrointestinal Microbiome, District of Columbia, Female, Humans, Male, Middle Aged, RNA, Ribosomal, 16S, Colorectal Neoplasms, Reproducibility of Results, Genome, Human, Case-Control Studies, Sequence Analysis, DNA
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