Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/1

study design

case-control
meta-analysis

Citation

PMID PubMed identifier for scientific articles.

27171425

DOI Digital object identifier for electronic documents.

10.1371/journal.pone.0155362

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865240/

Authors

Vogtmann E, Hua X, Zeller G, Sunagawa S, Voigt AY, Hercog R, Goedert JJ, Shi J, Bork P, Sinha R

Journal

PloS one

Year

2016

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.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/1

Curated date: 2022/01/31

Curator: Itslanapark

Revision editor(s): Itslanapark, Claregrieve1, WikiWorks, Peace Sandy

Subjects

Location of subjects: France; 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: control subjects

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: pre treatment colorectal cancer cases

Group 0 sample size Number of subjects in the control (unexposed) group: 94

Group 1 sample size Number of subjects in the case (exposed) group: 47

Lab analysis

Sequencing type: 16S

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

Matched on Factors on which subjects have been matched on in a case-control study: body mass index, sex

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, sex

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/1

Curated date: 2022/02/03

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Source: Table 3

Description: Differential microbial abundance between CRC cases and controls using 16S sequencing

Abundance in Group 1: decreased abundance in CRC cases

NCBI	Quality Control	Links
Clostridia
Coprococcus
Lachnospiraceae

Revision editor(s): Itslanapark, Claregrieve1