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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Structure, function and diversity of the healthy human microbiome
The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11234 · Cited by 11,726
A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624
KEGG for linking genomes to life and the environment
Kanehisa, M. I., Araki, M., Goto, S., Hattori, M., Hirakawa, M., Itoh, M., Katayama, T., Kawashima, S., Okuda, S., Tokimatsu, T., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm882 · Cited by 6,828
A metagenome-wide association study of gut microbiota in type 2 diabetes
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012) · Nature · doi:10.1038/nature11450 · Cited by 6,762
Richness of human gut microbiome correlates with metabolic markers
Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J.-M., Kennedy, S., et al. (2013) · Nature · doi:10.1038/nature12506 · Cited by 4,662
Self-citationGut metagenome in European women with normal, impaired and diabetic glucose control
Karlsson, F. H., Tremaroli, V., Nookaew, I., Bergström, G., Behre, C. J., Fagerberg, B., Nielsen, J., & Bäckhed, F. (2013) · Nature · doi:10.1038/nature12198 · Cited by 3,115
The gut microbiota, bacterial metabolites and colorectal cancer
Louis, P., Hold, G. L., & Flint, H. J. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3344 · Cited by 2,925
Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
MetaHIT consortium, Forslund, K., Hildebrand, F., Nielsen, T., Falony, G., Le Chatelier, E., Sunagawa, S., Prifti, E., Vieira-Silva, S., Gudmundsdottir, V., et al. (2015) · Nature · doi:10.1038/nature15766 · Cited by 2,116
Self-citationGut microbiome development along the colorectal adenoma-carcinoma sequence
Feng, Q., Liang, S., Jia, H., Stadlmayr, A., Tang, L., Lan, Z., Zhang, D., Xia, H., Xu, X., Jie, Z., et al. (2015) · Nature Communications · doi:10.1038/ncomms7528 · Cited by 1,506
Potential of fecal microbiota for early-stage detection of colorectal cancer
Zeller, G., Tap, J., Voigt, A. Y., Sunagawa, S., Kultima, J. R., Costea, P. I., Amiot, A., Böhm, J., Brunetti, F., Habermann, N., et al. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145645 · Cited by 1,375
Self-citationYu, J. Q., Feng, Q., Wong, S. H., Zhang, D., Liang, Q. Y., Qin, Y., Tang, L., Zhao, H., Stenvang, J., Li, Y., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309800 · Cited by 1,273
Human Gut Microbiome and Risk for Colorectal Cancer
Ahn, J., Sinha, R., Pei, Z., Dominianni, C., Wu, J., Shi, J., Goedert, J. J., Hayes, R. B., & Yang, L. (2013) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djt300 · Cited by 947
Self-citationRelating the metatranscriptome and metagenome of the human gut
Franzosa, E. A., Morgan, X. C., Segata, N., Waldron, L., Reyes, J. A., Earl, A. M., Giannoukos, G., Boylan, M. R., Ciulla, D., Gevers, D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319284111 · Cited by 731
Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults
Weir, T. L., Manter, D. K., Sheflin, A. M., Barnett, B. A., Heuberger, A. L., & Ryan, E. P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070803 · Cited by 642
The human gut microbiome as a screening tool for colorectal cancer
Zackular, J. P., Rogers, M. A. M., Ruffin, M. T., & Schloss, P. D. (2014) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-14-0129 · Cited by 551
Metagenomic species profiling using universal phylogenetic marker genes
Sunagawa, S., Mende, D. R., Zeller, G., Izquierdo-Carrasco, F., Berger, S. A., Kultima, J. R., Coelho, L. P., Arumugam, M., Tap, J., Nielsen, H. B., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2693 · Cited by 524
Self-citationLauber, C. L., Zhou, N., Gordon, J. I., Knight, R. D., & Fierer, N. (2010) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2010.01965.x · Cited by 474
Dysbiosis Signature of Fecal Microbiota in Colorectal Cancer Patients
Wu, N., Yang, X., Zhang, R., Li, J., Xiao, X., Hu, Y., Chen, Y., Yang, F., Lu, N., Wang, Z., et al. (2013) · Microbial Ecology · doi:10.1007/s00248-013-0245-9 · Cited by 454
A metagenomic insight into our gut's microbiome
Lepage, P., Leclerc, M., Joossens, M., Mondot, S., Blottière, H. M., Raes, J., Ehrlich, S. D., & Dore, J. M. (2012) · Gut · doi:10.1136/gutjnl-2011-301805 · Cited by 371
Accurate and universal delineation of prokaryotic species
Mende, D. R., Sunagawa, S., Zeller, G., & Bork, P. (2013) · Nature Methods · doi:10.1038/nmeth.2575 · Cited by 327
Self-citationThe microbiome quality control project: baseline study design and future directions
Sinha, R. R., Abnet, C. C., White, O. R., Knight, R. D., & Huttenhower, C. (2015) · Genome biology · doi:10.1186/s13059-015-0841-8 · Cited by 281
Self-citationMira‐Pascual, L., Cabrera‐Rubio, R., Ocon, S. M., Costales, P., Parra, A., Suárez, A., Morís, F., Rodrigo, L., Mira, Á., & Collado, M. C. (2014) · Journal of Gastroenterology · doi:10.1007/s00535-014-0963-x · Cited by 269
Carroll, I. M., Ringel‐Kulka, T., Siddle, J. P., Klaenhammer, T. R., & Ringel, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046953 · Cited by 241
Epidemiologic studies of the human microbiome and cancer
Vogtmann, E., & Goedert, J. J. (2016) · British Journal of Cancer · doi:10.1038/bjc.2015.465 · Cited by 212
Self-citationMOCAT: A Metagenomics Assembly and Gene Prediction Toolkit
Kultima, J. R., Sunagawa, S., Li, J., Chen, W., Chen, H., Mende, D. R., Arumugam, M., Pan, Q., Liu, B., Qin, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047656 · Cited by 204
Self-citationCollecting Fecal Samples for Microbiome Analyses in Epidemiology Studies
Sinha, R. R., Chen, J., Amir, A., Vogtmann, E., Shi, J., Inman, K. S., Flores, R., Sampson, J. N., Knight, R. D., & Chia, N. (2015) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-15-0951 · Cited by 198
Self-citationTemporal and technical variability of human gut metagenomes
Voigt, A. Y., Costea, P. I., Kultima, J. R., Li, S. S., Zeller, G., Sunagawa, S., & Bork, P. (2015) · Genome biology · doi:10.1186/s13059-015-0639-8 · Cited by 182
Self-citationComparison of methods for fecal microbiome biospecimen collection
Dominianni, C., Wu, J., Hayes, R. B., & Ahn, J. (2014) · BMC Microbiology · doi:10.1186/1471-2180-14-103 · Cited by 170
Collection media and delayed freezing effects on microbial composition of human stool
Flores, R., Shi, J., Yu, G., Ma, B., Ravel, J., Goedert, J. J., & Sinha, R. R. (2015) · Microbiome · doi:10.1186/s40168-015-0092-7 · Cited by 141
Self-citationCase-control study of colorectal cancer and fecapentaene excretion.
SCHIFFMAN, M. H., Tassell, R. L. V., Robinson, A., Smith, L., Daniel, J., Hoover, R., Weil, R., Rosenthal, J. F., Nair, P. P., & Schwartz, S. (1989) · PubMed · Cited by 36
Lewis, Z. T., Davis, J. C. C., Smilowitz, J. T., German, J. B., Lebrilla, C. B., & Mills, D. A. (2016) · PeerJ · doi:10.7717/peerj.1612 · Cited by 15
Flagged first, then by citations
1 of the 32 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- J Oksanen, 2007, The vegan package, Community ecology package, 631
Cited by
Sorted by citations
Role of the gut microbiota in nutrition and health
Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018) · BMJ · doi:10.1136/bmj.k2179 · Cited by 2,375
Beghini, F., McIver, L. J., Blanco-Míguez, A., Dubois, L., Asnicar, F., Maharjan, S., Mailyan, A., Manghi, P., Scholz, M., Thomas, A. M., et al. (2021) · eLife · doi:10.7554/elife.65088 · Cited by 2,303
Ferretti, P., Pasolli, E., Tett, A., Asnicar, F., Gorfer, V., Fedi, S., Armanini, F., Truong, D. T., Manara, S., Zolfo, M., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.06.005 · Cited by 1,292
Wirbel, J., Pyl, P. T., Kartal, E., Zych, K., Kashani, A., Milanese, A., Fleck, J. S., Voigt, A. Y., Palleja, A., Ponnudurai, R., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0406-6 · Cited by 1,373
Self-citationThomas, A. M., Manghi, P., Asnicar, F., Pasolli, E., Armanini, F., Zolfo, M., Beghini, F., Manara, S., Karcher, N., Pozzi, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0405-7 · Cited by 1,030
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
